Title of Invention

"AN IMPROVED FUEL EFFICIENT COMMERCIAL LP-GAS BURNER"

Abstract

Novel substituted 1,2,4 trioxanes useful as anti malarial agent and a process for the preparation of the same Novel substituted 1,2,4 trioxanes useful as antimalarial agent and a process for the preparation of the same by reacting hydroxyacetophenones with α-haloesters in the presence of a base optionally in an organic solvent at a temperature in the range of room temperature of refluxing temperature to give keto-esters, reacting keto-esters under Reformatsky condition in an aprotic organic solvent in the temperature range of room temperature to refluxing temperature to give β-hydroxyesters; dehydrating β-hydroxyesters; dehydrating β-hydroxyesters using a catalyst in an organic solvent at a temperature in the range of room temperature to refluxing temperature to give a,p-unsaturated esters ; reducing β-hydroxyesters esters with a complex metal hydride such as LiAIH4 in an ether solvent at a temperature in the range of 0°C to room temperature to give allylic alcohols ; oxygenation of allylic alcohols in presence of a sensitizer in an organic solvent at a temperature in the range of -10°C to room temperature to give β-hydroxyhydroperoxides ; isolating and then reacting or reaction in situ β-hydroxyhydroperoxides with compounds containing aldehyde or ketone group in presence of an acid catalyst in an organic solvent at a temperature in the range of 0°C to room temperature to give hydroxyl-functionalized 1,2,4-trioxanes with an acid chloride or anhydrides in presence of a base in an organic solvent at a temperature in the range of 0°C to room temperature to give trioxane esters.

Full Text

This invention relates to novel substituted 1,2,4-trioxanes useful as antimalarials. This invention also relates to a process for the preparation of novel substituted 1,2,4-trioxanes. This invention paniculariy relates to a process for the preparation of 6-[α-(hydroxyalkoxy substituted aryl)vinyl]-l,2,4-trioxanes and their esters as new aritimalarial agents. More particularly the present invention provides a process for the preparation of hydroxy-functionalized trioxanes and their esters of general formula 1, wherein Rt and R2 represent hydrogen, alkyl group such as methyl, (Figure Removed) ethyl, propyl ; R3 and R4 represent hydrogen, alkyl group such as methyl, ethyl, aryl such as phenyl, naphthyl or part of a cyclic system ; R3 represents hydrogen, alkyl group such as methyl, ethyl, propyl, aryl such as phenyl or a carboxy alkyl group such as CH2CH2CO2H ; X represents hydrogen or lower alkoxy such as OMe, Z represents O or OCO. These compounds have been tested against multi-drug resistant P. yoelii in mice and several of them show promising antimalarial activity. Some of these compound with promising antimalarial activity have been tested against P. cynomolgi in monkeys and have been found effective. The invention thus relates to pharmaceutical industry. The trioxanes of general formula 1 are new chemical entities and they have not been prepared earlier. Trioxanes of general formula 1 are oil-soluble and can be administered as solution in oil such as groundnut oil. Some of the compounds of formula 1 are hemisuccinate derivatives and are soluble both in oil and aqueous NaHCO3 solution and can be administered as a solution in groundnut oil or aqueous NaHC03. The mode of administration can be oral, intramuscular, subcutaneous or intravenous. The main objective of this invention is to provide novel substituted 1,2,4-trioxanes useful as antimalariais. The objective of the present invention is also to provide a process for the preparation of novel substituted 1,2,4-trioxanes. The another objective of the present invention is to provide a process for the preparation of hydroxy-functinalized trioxanes and their esters of general formula 1, a new series of antimalarial agents. Accordingly, the present invention provides a process for the preparation of novel substituted 1,2,4-trioxanes and their esters of general formula 1 which comprises reacting hydroxyacetophenones of formula 2 wherein X represents hydrogen or lower alkoxy such as OMe, with α-haloesters of formula 3 wherein R1 and R2 represent hydrogen, alleyl group such as methyl, ethyl, propyl and Y represnts halogen such as Cl or Br, in the presence of a base optionally in an organic solvent at a temperature in the range range of room temperature to refluxing temperature to give keto-esters of general formula 4, wherein R1, R2 and X have the same meaning as above; reacting keto-esters of general formula 4 under Reformatsky condition in an aprotic organic solvent in the temperature range of room temperature to refluxing temperature to give p-hydroxyesters of general formula 5, wherein Rh R2 and X have the same meaning as above ; dehydrating p-hydroxyesters of formula 5 using a catalyst in an organic solvent at a temperature in the range of room temperature to refluxing temperature to give α,β-unsaturated esters of general formula 6, wherein RI, R2 and X have the same meaning as above ; reducing a,p-unsaturated esters of general formula 6 with a complex metal hydride such as LiAlELt in an ether solvent at a temperature in the range of 0°C to room temperature to give allylic alcohols of formula 7 wherein R1, R2, X have the same meaning as above ; oxygenation of allylic alcohols of formula 7 in presence of a sensitizer in an organic solvent at a temperature in the range of -10°C to room temperature to give p-hydroxyhydroper oxides of general formula 8 wherein RI, R2, X have the same meaning above ; isolating and then reacting or reacting in situ p-hydroxyhydroperoxides of formula § with compounds containing aldehyde or ketone group in presence of an acid catalyst in an organic solvent at a temperature in the range of 0°C to room temperature to give hydroxy-fiictionalized 1,2,4-trioxanes of general formula 1, wherein RI, R2 and X have the same meaning as above, R3, R4 are hydrogen, alkyl group such as methyl, propyl, aryl group such as phenyl, naphthy! or part of a cyclic system, Rj is H and Zis 0 ; reacting hydroxy-functionalized trioxanes of general formula 1, wherein R is H and Z is 0 with an acid chloride or anhydrides in presence of a base in an organic solvent at a temperature in the range of 0°C to room temperature to give trioxane esters of genera! formula 1, wherein RI, R2, R3, R, and X have the same meaning as above, R3 is alkyl group such as methyl, ethyl, propyl, aryl group such as phenyl, carboxyalkyl such as CH2CH2C02H; Z is 0-CO. In the process hydroxyacetophenones of formula 2 are reacted with a-haloesters of formula 3 in presence of a base such as Na2C03, K2C03, KHC03, in an organic solvent such as acetone, dimethylformamide, dimethylsulfoxide or without solvent, to give ketoesters of general formula 4. These ketoesters can be isolated and purified by standard laboratory methods such as crystallization or chromatography using an adsorbent such as silica gel. All ketoesters of general formula 4 except lla (formula 11, RI = R2 = X = H), lie (formula 11, R, = H, R2 = Me, X = H) and 12a (formula 12, R, = R2 = H) are new compounds and they have not been prepared earlier. Ketoesters lla, lie and 12a are known compounds, [(a) Chim, Ther., 8, 574 (1973), Indian J. Oiem., 24, 119 (1985), Chen-Abstracts, 124, 8616e (1996)]. In the process ketoesters of general formula 4 are reacted with ethyl bromoacetate and Zn in an aprotic solvent such as benzene, diethyl ether, to give p-hydroxyesters of general formula 5. These p-hydroxyesters can be isolated and purified by standard laboratory methods such as column chromatography using an adsorbent such as silica gel and a hydrocarbon solvent in combination with ethyl acetate as eluent or can be used without purification in the next step, p-hydroxyesters of general formula 5 are new compounds and they have not been prepared earlier. These hydroxy esters of general formula S have an additional ester group as part of substitution in the aromatic ring. In the process dehydration of p-hydroxyesters of geneal formula 5 is accomplished in an hydrocarbon solvent such as benzene, toluene, CH2C12, in the presence of a catalyst such as I2, p-toluenesulfonic acid, P205, or acidic resin such as Amberlyst-15 to give a,p-unsaturated esters of general formula 6. These unsaturated esters can be isolated and purified by standard laboratory methods such as chromatography using an adsorbent such as silica gel. a,p-Unsaturated esters of general formula 6 have an addition ester group as part of substitution in the aromatic ring. These esters of general formula 6 are new compounds and they have not been prepared earlier. In the process reduction of and unsaturated esters of general formula 6 is done by reacting the compound with a complex metal hydride such as LiAlHL4 in an ether solvent such as diethyl ether, THF, to give allylic alcohols of general formula 7. These allylic alcohols of general formula 7 have an addition hydroxyl group as hydroxyalkoxy substitution in the aromatic ring. These allylic alcohols of general formula 7 can be isolated and purified by standard laboratory methods such as chromatography using an adsorbent, such as silica gel and a hydrocarbon solvent in combination with ethyl acetate as eluant. Compounds of general formula 7 are new chemical entities and they have not been prepared earlier. In the process allylic alcohols of general formula 7 are converted to p-hydroxyhydroperoxides of formula 8 by passing oxygen gas in the solution of the alcohol in an organic solvent and in the presence of a dye and a light source which provides visible light. The dye which acts as a sensitizer i.e. converts triplet oxygen to highly reactive singlet oxygen, may be such as methylene blue, Rose Bengal, tetraphenylporpliine. Organic solvent used maybe such as CH2C12, CH3CN, acetone, methanol, benzene. These p-hydroxyhydroperoxides of general formula § can be isolated and purified by known laboratory1 methods or can be used in situ, without purification and isolation, in the next step. These p-hydroxyhydroperoxides of formula 8 are new chemical entities and they have not been prepared earlier. Furthermore, these p-hydroxyhydroperoxides have an extra hydroxyl group in the form of hydroxyalkoxy substitution in the aromatic ring. The novel feature of these p-hydroxyhydroperoxides is that this extra hydroxy! group which is present as a hydroxyalkoxy substituent in the aromatic ring, does not take part in the next reaction i.e. condensation of hydroperoxides with aldehyde and ketones and thus provide 1,2,4-trioxanes which carry a hydroxy group suitable for further derivatization. In the process B-hydroxyhydroperoxides of general formula 8 are converted lo hydroxy-fimctionalized 1,2,4-trioxanes of general formula 1 (Rs = H, Z = 0) by reacting these hydroperoxides with carbonyl compounds of formula 21-22 in presence of an acid catalyst in an aprotic organic solvent. The carbonyi compounds used may be such as benzaidehyde, naphthaldehyde, acetone, ethyl msthyl ketone, methyl propyl ketone, methyl isobutyl ketone. 4-heptanone, 5-nonanone, 6-undecanone, dibenzyl ketone and the such as, cyclic ketone such as cyciopentanone, cyclohexanone, cycloheptanone, bicyclic ketone such as norcomphor (22a) and tricyclic ketone such as 2-adamantanone (22b). The acid catalyst used may be HC1, HaSO^, p-toiuene sultbraic acid, BF3.OEt2, acidic resin such as Amberlyst-15. The organic solvent used may be CH2C12, CHC!3, benzene, CH3CN. These trioxanes of general formula 1 (R5 = H, Z = O) are stable compounds and can be isolated and purified by standard chromatographic techniques using an adsorbent such as silica gel and a hydrocarbon solvent in combination with polar organic solvent as eluaat. These trioxanes of general formula 1 (R5 = H, Z = 0) are new chemical entities and they have not been prepared earlier. The novel feature of these trioxanes is that they are equipped with a primary hydroxyi group suitable for making derivatives of these trioxanes. This hydroxyl group is part ofalkoxy substituent in the aromatic ring. These trioxanes of general formula 1 (Rj = H, Z = O) have been tested against malarial parasites in animal models and several of them show very promising antimalarial activity, both against chloroquine sensitive and chloroquine resistant malaria. Tliese trioxanes are oil-soluble and can be administered as solution in oil such as groundnut oil. Some of these trioxanes have shown significant gamatocidal activity. In the process reaction of trioxanes of general formula 1 (R3 - H, Z = O) with acid chlorides of formula 29 or acid anhydrides of formula 30 wherein R5 is alkyl group such as methyl, ethyl, propyl, aryl group such as phenyl, is done in an aprotic organic solvent in the presence of a base to give trioxane esters of general formula 1 wherein R5 is alkyi group such as methyl, ethyl, propyl, atyl group such as phenyl, Z is OCO. In the reaction hydroxyl group of trioxanes of formula 1 (R3 = H, Z = 0) is esterified. The acid chlorides and acid anhydrides used may be such as acetyl chloride, benzoyl chloride, propionic anhydride, butyric anhydride, heptanoic anhdride. The base can be such as EtjN, pyridine, with or without the catalyst such as 4-dimethylaminopyridine (DMAP). The organic solvent used may be such as CH2C12, CHC13, THF, CH3CN. These trioxanes of general formula 1 (R, = alkyi, aryl, Z = OCO) can be isolated and purified by known laboratory methods such as crystallization or chromatography using an adsorbent such as silica gel and hydrocarbon solvent hi combination with polar organic solvents as eluant The trioxanes are new chemical entities and they have not been prepared earlier. These trioxanes are oil-soluble and can be administered as solution in edible oil such as groundnut oil. Some of the trioxanes of general formula 1 (Rj = alkyi, aryl, Z = OCO) have shown promising antimalarial activity in animal models. In the process trioxanes of formula 1 (R5 = H, Z = 0) are reacted with succinic anhydride in an aprotic solvent in presence of tertiary amine with or without the presence of 4-dimethylaminopyridine (DMAP) to give carboxy fimctionalized trioxanes of general formula 1 (R = CH2CH2CO2H, Z = OCO). The tertiary amine may be such as Et3N, pyridine. Aprotic organic solvent may be such as CH2C12, CHC13, CH3CN, toluene. THF. In the reaction, the hydroxyl group of the trioxanes 1 (Rj - H, Z - 0) is esterified. The trioxanes of general formula 1 (R5 = CH2CH2C02H, Z = OCO) have a carboxyl group and are soluble in aqueous bicarbonate or carbonate solutions. Thus they can be administered both as solution in oil or aqueous bicarbonate/carbonate solutions. Trioxanes of general formula 1 (R3 = CH2CH2C02H, Z = OCO) can be isolated and purified by known laboratory methods such as given above. Trioxanes of general formula 1 (R5 = CH2CH2C02H, Z = OCO) are new chemical entities and they have not been prepared earlier. Some of these trioxanes have shown promising antimalarial activity against both chloroquine-sensitive and resistant malaria in animal models. Some of these trioxanes also show significant gamatocidal activity. The invention is further illustrated by the following examples which should not, however, be construed to limit the scope of the present invention. Example 1 Ethyl (4-acetylpheaoxy)acetate (compound lla, formula 11, R1 = R2= X = H) A mixture of p-hydroxyacetophenone (50 g), ethyl chloroacetate (60 ml), K2C03 (120 g) in acetone (450 ml) was refluxed with stirring for 24 h. The reaction mixture was filtered and the residue was washed with acetone. The combined filterate was concentrated and the residue was redissolved in ether, the ether extract was washed with aqueous NaOH, and men with water, dried, concentrated and purified by chromatography on silica gel using hexane - ethylacetatu as eluant to give 65.3 g (77% yield) of lla, m.p.64-68°C. Compound lla was also prepared using the conditions as given in table 1. Table 1 (Table Removed) p-Hydroxyester 13a (formula 13, Rl = R2 = X » H) To a mixture of ketoester lla (20 g) zinc metal (12 g), I2 (20 mg) in benzene was added ethyl bromoacetate (10 ml) dropwise. Hie reaction mixture was refluxed for another 7 hr, cooled, acidified with aqueous HCl, benzene layer was separated and the aqueous layer was extracted with benzene. Combined organic extract was washed with water and then aqueous NaHC03, dried and concentrated. The crude product was purified by column chromatography on silica gel using mixture of hsxane and ethylacetote as eluant to furnish 13a (63% yield) of p-hydroxyester as an oil. Compound 13a was also prepared using the conditions given in table 2, Table 2 (Table Removed) a,p-Unsaturated ester 15a (formula IS, Rt = R2 = X = H) A mixture of p-hydroxyester 13a (10 g) and P2O5 (4 g) in benzene (150 ml) was refluxed for 2.5 h. The reaction mixture was filtered and the filtrate was concentrated to give 10 g of crude product which was purified by column chromatography on silica gel using hexane - ethylacetate as eluant to give 5.13 g (56% yield) of a,p-unsaturated ester 15a as an oil. Allylic alcohol 17a (formula 17, R1 = R2 = X = H) To a stirred and ice-cooled mixture of LiAlHi (6 g) in dry ether (400 ml) was added dropwise a solution of α-β-iuisaturated ester 15 a (12 g) in ether. The reaction mixture was stirred in ice-bath for 5 h, and then quenched with water and 10% NaOH. The organic layer was separated, dried on Na2S04 and concentrated to give 8.84 g of crude product which was purified by column chromatography to furnish 5.67 g (59%) of allylic alcohol 17a; m.p. 83-86°C. 3-[4-(2-Hydroxyethoxy)phenyI]-l-hydroxy-but-3-en-2-hydroperoxide (compound 19a. general formula 19, R, = R2 = H, X = H) (1) A solution of allylic alcohol 17a and methylene blue (15 mg) in ethanol (60 ml) was irradition with a 250 watt tungston-halogen lamp al -10°C while a slow stream oxygen was passed through the reaction mixture for 9.5 h. The reaction mixture was diluted with water and extracted with ether. The ether extract was conceiitrated and the crade product was chromatographed on silica gel using CH2C12 - ether as eluant to give 650 mg (28% yield) of β-hydroxyhydroperoxide 19a. (2) A solution of allylic alcohol 17a (1 g), tetraphenylporphine (50 mg) in CHC1:, (60 ml) was photooxygenated at r.t. for 6 h. p-Hydroxyhydroperoxide 19a separated as a solid. It was washed with ether to give 500 mg (44% yield) of tlc pure 19a. Tiioxane 23al (formula 23, R1 = R2 = X = H, R3, R4 = -CH2CH2CH2CH2) (1) Two-pot procedure : A mixture of p-hydroxybydroperoxide 19a (900 rag), cyclopentanoue (2 ml) and p-toluene sulfonic acid (50 nig) in acetonitrile (10 nil) was stirred at room temperature for 3.5 h. The reaction mixture\was diluted with saturated aqueous NaHC03 and extracted with etlier. The ether extract was concentrated and the crude product was purified by chromatography (elution with ethylacetate-hexane ; 1 : 9) to furnish 310 mg (44% yield) of trioxane 23al. (2) One-pot procedure: A solution of alcohol 17a (3.5 R) and methylene blue (10 mg) in CH3CN (65 ml) was irradiation with a tangston halogen lamp at 0°C for 7.5 h when a slow stream of oxygen was passed through the reaction mixture to give p-hydroxyhydroperoxide 19a as indicated by.TLC. To the reaction mixture were added cyclopentanone (6 ml) and p-toluenesulfonic acid (50 mg) and the reaction mixture was stirred at r.t. for 2 days. Workup and purification by chromatography furnished 1.14 g (23% yield based on alcohol 17a) of trioxane 23al. Acetate of trioxane 23al [compound 31al, formula 31, R1 = R2 = H ; R3, R4 = CH2CH2CH2CH2 ; RS = CH3;X=H] A solution of trioxane 23al (200 mg) in pyridine (6 ml) was treated with acetic anhydride (0.5 ml) and the resulting mixture was left in refrigerator (~ 5°C) overnight. The reaction mixture was diluted with water and extracted with ether. Ether extract was washed sequencially with water, 10% HC1, water, and then dried (Na2S04) and concentrated. The crude product was purified by column chromatography on silica gel to give 180 mg (91% yield) compound 26al as an oil. Example 2 Benzoate of trioxane 23al [compound 31a5, formula 31, Rj= R2 = H ; R3, R, = CH2CH2CH2CH2 ; R5=Ph;X=H] A solution of trioxane 23al (180 mg) and benzoyl chloride (0.5 ml) in pyridine (3 ml) was left at r.t. overnigllt. The reaction mixture was diluted with water, extracted with ether, Ether extract on usual processing followed by column chromatography on silica gel using hexane - ethyl acetate as ejuant furnished 100 mg (42% yield) of benzoate 31a5 as an oil. Example 3 Trioxane 23a2 (formula 23, R, = R2 = X = H, R3, R, = -CH2CH2CH2CH2CH2-) A solution of allylic alcohol 17a (1 g) and methylene blue (15 mg) in acetonitrile was photooxygenated at 0°C for 6.5 h. as above and then reacted with cyclohexanone (2 ml) using p-toluenesulfonic acid as catalyst at r.t. for 5 h. The crude product obtained after workup as above was purified by clironiatography to give 0.86 g (57% yield based on the alcohol 17a) to furnish 1,2.4-trioxane 23a2. Example 4 Trioxane 23a3 (formula 23, Rt = R2 = X = H ; R3 = R, =W) (1) From p-hydroxyhydroperoxide 19a To a solution of p-hydroxyhydroperoxide 19a (100 mg) in a acetone (5 ml) was added one drop of cone. HC1 and the reaction mixture was stirred at r.t. for 30 minutes. The reaction mixture was concentrated under vacuum and the crude product was purified by clironiatography on silica gel using hexane - ethylacetate as eluant to give 60 mg (52% yield") of trioxane 23a3. (2) From allylic alcohol 17a A soiition of allylic alcohol 17a (1 g) and Rose Bengal (5 nig) in acetone (40 ml) was photooxygenated at -8°C for 6 IL To this reaction mixture were added 3 drops of cone. HC1 and the reaction mixture was left overnight at r.t. The solvent was removed under vacuum and the crude product was chromatographed on silica gel as above to furnish 340 mg (26% yield based on allylic alcohol 17a) of trioxane 23a3. Example 5 Trioxane 27a (formula 27, Rt = R2 = X = H) A. solution of allylic alcohol 17a (2 g) and methylene blue (5 mg) in CH3CN (60 ml) was photooxygenated at 0°C for 6 h to give p-hydroxyhydroperoxide 19a as indicated by TLC. To this reaction mixture 2-adamantanone (2 g) was added and the reaction mixture was stirred for 1 h when p-toluenesulfonic acid (10 mg) was added and the reaction mixture was stirred for another 6 h at room temperature. The reaction was quenched with aqueous NaHC03, diluted with water and extracted with ether. Ether extract was washed with water, dried (Na2SO4) concentrated aud the crude product was purified by chromatography on silica gel to furnish 1.9 g (57% yield based on alcohol 17a) of trioxane 27a as an oil. Acetate of trioxane 27a [compound 35al, formula 35, RI = R2 = H ; R5 = CH3 ; X = H] A mixture of trioxane 27a (200 mg), acetic anhydride (1 ml) in pyridine (4 ml) was left at r.t. overnight. The reaction mixture was diluted with water and extracted with ether. Ether extract was washed with water, 10% aqueous HC1, water, dried (Na2S04) and concentrated to give 200 mg of crude product which was purified by chromatography on silica gel (8 g, elution with 50% EtoAc in CH2C12) to give 178 mg (80% yield) of acetate 35al as an oil. Hemisuccinate of trioxane 27a [compound 41a, formula 41, R1 = R2 = H ; X = H] A mixture of trioxaiie 27a (2 g) and succinic anhydride (3 g) in pyridine (20 ml) was left at r.t. overnight The reaction mixture was diluted with water and extracted with ether. The extract was washed with water, 10% HC1, water, dried (Na2SO4) and concentrated to give 2.3 g of crude product which was purified by chromatography on silica gel (25 g, eluted with 50% ether in CH2C12) to give 1.5 g (60% yield) of hemisuccinate 41a as a highly viscous material. Example 6 Trioxane 23al3 (formula 23, R4 = R2 = X = H ; R3, R4 = H, 1-naphthyl) A solution of allylic alcohol 17a (1.0 g) and methylene blue (70 mg) in CH3CN (50 ml) was photooxygenated at -10 to 0°C for 6 h. To one-half of this reaction mixture were added 1-naphthaldehyde (1 ml) and p-toluene sulfonic acid (20 mg) and the reaction mixture was kept at 5°C overnight. Usual workup followed by purification by chromatography furnished trioxane 17al3) in 32% yield. Hemisuccinate of trioxane 23al3 [compound 37a4, formula 37, Rj = R2 = H ; R3, R» -" H, 1-naphthyl; X=H] To an ice-cooled mixture of 23al3 (120 mg) and succinic anhydride (200 mg) in CH2C12 (20 ml) were added triethylamine (0.2 nil) and 4-dimethylaminopyridine (30 mg) and the reaction mixture was left overnight at r.t. Workup as above followed by column chromatography on silica gel using CH2C12 - ether as eluant furnished hemisuccinate 37a4 as an oil (100 mg ; 67% yield). Example 7 Ethyl 2~(4-acetylphenoxy)isobutyrate (compound lib Formula 11, Rl = R2 = Me ; X = H) A mixture of p-hydroxyacetophenone (14 g), ethyl 2-bromoisobutyrate (21 g) and K2C03 (40 g) in acetone (260 ml) was refluxed with stirring for 19 h. The reaction mixture was diluted with water and extracted with benzene. Usual processing of the benzene extract furnished 10.5 g (41% yield) of keto ester 11b as an oil. Compound 11b was also prepared using the conditions as given in table 3. Table 3 (Table Removed) β-Hydroxyester 13b (formula 13, R1, = R2 = Me, X = H) To arefluxing mixture ofketoester lib (12g), zinc (6 g), I2 (70 mg) in benzene (200 ml) was added dropwise ethyl bromoacetate (7 ml) and the reaction mixture was refluxed for 7 hr. Work up and purification by chromatography on silica gel (hexane - EtoAc on eluant) furnished 45% yield ofp-hydroxyester 13b. α,βUnsatiirated ester 15b (formula 15, R1 = R2 = Me, X = X) To a refluxing mixture of ketoesler life (10.5 g), zinc (5 g), I2 (40 mg) in benzene (200 ml) was added, dropwise a solution of ethyl bromoacetate (5 ml) in benzene (50 ml) and the reaction mixture was refluxed for 7 h. The reaction mixture was cooled and acidified with 10% aqueous HC1. Benzene layer was separated and the aqueous layer was extracted with benzene (2 x 150 nil). The combined organic extract was washed with water and aqueous NaIiC03 solution, dried (Na2S04) and concentrated to give p-hydroxyester 13b which was; used in the next without isolation and purification. The crude 13b as obtained above was dissolved in benzene (200 ml), I2 (50 mg) was added the reaction mixture was refluxed for 1.75 h. The reaction mixture was cooled, washed with aqueous sodium thiosulphate and then with water, dried (Na2S04) and concentrated. The crude product was purified by colurrai chromuiography to furnish 6.80 g (51% yield) of a,|3-unsaturated ester iSb. Allylic alcohol 17b (fonnula 17, R1= R2 = Me ; X = H) To a stirred and ice-cooled mixture of LiAlH, (5 g) in dry ether (450 ml) was added dropwise a solution of α,β-unsahirated ester 15b (6.2 g) in dry ether. The reaction mixture was stirred for 5 h. and then quenched with water and 10% aqueous NaOH. The organic layer was separated. The residue was washed with ether and the combined organic extract was dried (Na2S04), concentrated and the crude product was purified to give 3.0 g (66% yield) of allylic alcohol 17b, as an oil. 3-[4-(2-Hydroxy-l,l-dimethyI-ethoxy)phenyl]-l-hydroxy-but-3-en-2-hydroperoxide (compound 19b, formula 19, R, = R2 = Me, X = H) A solution of allylic alcohol 17b (1.40 g) and methylene blue (100 mg) in CH3CN (45 ml) was irradiated with a 500 watt tungsten-halogen lamp at 0°C for 5 h while a slow stream of oxygen was passed tlirough the reaction mixture. The reaction mixture was concentrated to 20 ml and then diluted with water (20 ml) and extracted with ether (3 x 25 ml). The combined ether extract was washed with water, dried (N^SCX), concentrated and purified by chromatography on silica gel to furnish 860 mg (61% yield) of p-hydroxyhydroperoxide 19b as an oil. Trioxane 23bl (formula 23, R1 = R2 = Me, X = H ; R3, R, = -CH2-CH2-CH2-CH2-) A slution of allylic alcohol 17b (680 mg) and methylene blue (15 mg) in CH^CN (60 ml) was photooxygenated at 0°C for 3.25 h to give p-hydroxyhydroperoxide 19b as indicated by TLC. This reaction mixture was divided into two equal parts. To one part were added cyclopentanone (2 ml) and PTSA (25 mg) and stirred at r.t. for 2.75 h. Usual workup followed by chromatography on silic gel furnished 240 mg (63% yield based on allylic alcohol 17b) of trioxane 23bl. Hemisnccinate of trioxane 23bl [compound 37bl, formula 37, R1 = R2 = Me ; R3, R^ ~ CH2CH2CH2CH2;X=H] A solution trioxane 23bl (1 g) in CH2C12 (40 mi) was reacted with succinic anhydride as above and the product was purified by chromatography as above to furnish 1.23 g (93% yield) of hemisuccinate 37bl. Example 8 Trioxane 23b2 (formula 23, R1 = R2 = Me, X = H ; R3, R, = -CH2-(CH2)3-CH2-) To one half of the photooxygenated mixture from the above example were added cyclohexanone (2 ml) and PTSA (25 mg) and the reaction mixture was stirred at r.t. for 2.75 h. Normal workup followed by purification by chromatography on silica gel column gave 230 mg (4694 yield based on the allylic alcohol 17b used) of trioxane 23b2. Example 9 Trioxane 27b (formula 27, R1 = R2 = Me, X = H) A mixture of allylic alcohol 17b (2.0 g) and methylene blue (100 mg) in CH3CN (60 ml) was photooxygenated at 0°C for 6.5 h. To this re action mixture were added 2-adamantanone (3.0g) and p- toluenesulfonic acid (100 rag) and the reaction mixture was left at room temperature overnight. The reaction mixture was quenched with aqueous NaHCO3, diluted with water and extracted with ether. The ether extract was washed with water, dried (Na2SO4) and concentrated. The crude product was purified by chromatography on silica gel column to give 1.61 g (59% yield based on allylic'alcohol I7b) of 1,2,4-trioxane 27b, m.p. 100-102°C. Trioxane 27b was obtained in 44% yield when the condensation with 2-adamantanone was done using Amberlyst-15 as catalyst. Acetate of trioxane 27b [compound 35bl, formula 35, Rj = R2 = Me; R5 = CH3; X = H] A solution of trioxane 27b (200 mg) and acetic anhydride (1 nil) in pyridine (4 ml) was reacted at r.t overnight. Workup as above followed by column chromatography on silica gel furnished 0.21 g of acetate 35bl as a viscous material. Example 10 Propionate of trioxane 27b [compound 35b2, formula 35, RI = R2 = Me ; R5 = Et; X = H] To an ice-cooled mixture of 27b (300 mg) and propionic anhydride (1.3 ml) in CH2C12 (10 ml) were added triethylamine (0.8 ml) and 4-dimethylaminopyridine (20 mg) and a left overnight at r.t. Usual workup as above followed by column chromatography on silica gel furnished 310 mg (91% yield) of propionate 35b2 as a colourless oil. Example 11 Hexanoate of trioxane 27b [compound 35b4, formula 35, RI = R2 = Me ; Rs = n-pentyl; X = H] A mixture of trioxane 27b (300 mg) and hexanoic anhydride (1 ml) in CH2C12 (15 ml) was reacted in presence of triethylamine (0.5 ml) and 4-dimethylamino pyridine (20 mg) at r.t for 1 h. Workup as above followed by column chromatography on silica gel furnished 330 mg (89% yield) of hexanoate 35b4 as an oil. Example 12 Hemisuccinate of trioxane 27b [compound 41b, formula 41, RI = R2 = Me ; X = H] To a stirred and ice-cooled mixture of trioxane 27b (2.3 g) and succinic anhydride (2.5 g) in CH2C12 (100 ml) were added triethylamine (2.5 ml) and 4-dimethylamino pyridine (50 mg) and the reaction mixture was stirred at r.t. for 2 h, concentrated under reduced pressure, acidified (50 ml of 10% HC1) and extracted with ether (3 x 150 ml). Ether extract was washed with water (3 x 100 ml), dried (Na2S04) and concentrated under reduced pessure to give 3.1 g of cnide material which was chromatographed on silica gel (50 g, eluted with 50% ether in hexane) to give 2.3 g solid which was crystallized from ether-hexae to give 1.91 g (68% yield) of hemisuccinate 41b as while crystals, tup. 96-99°C. Similar yields of 41b were obtained when the reaction was done in absence of 4- dimethylaminopyridine. Example 13 Ketoester llf (formula 11, R, = R2 = H, X = Ome) Compound llf was prepared from 3-methoxy-4-hydroxyacetophenone (formula 9, X = Ome) in 84% yield following the procedure used for the preparation of compound lla as given in example 1. p-Hydroxyester 13f (formula 13, R1, = R2 = H, X = OMe) To arefluxing mixture of ketoester llg (21 g), zinc (6 g), and catalytic amount of iodine in benzene (400 ml) was added dropwise ethyl bromoacetate (15 ml) and the reaction mixture was refluxed for 8 hr. Work up and purification as given in example 1 furnished 20 g (71% yield) of p-hydroxyester 13f. α,β-Unsaturated ester I5f (formula 15, R1 = R2 = H, X = OMe) p-Hydroxyester 13f (20 g) was dehydrated with P205 in refluxing benzene as above and the crude product was purified by column chromatography on silica gel to furnish 10.5 g (55%) of a,p-unsaturated ester ISf. Allylic alcohol 17f (formula 17, R1 = R2 = H ; X = OMe) a,p-Unsaturated ester 15f (1.2 g) was reduced with LiAIh4 (240 mg) in dry ether (25 ml) at 0°C. Work and purification was done according to the procedure as given above to give 260 mg (29% yield) of allylic alcohol 17f. Trioxane 27f (formula 27, R1 = R2 = H ; X = OMe) A solution of allylic alcohol 17f (550 mg), adamantanone (540 mg) and methylene blue (15 ing) in CH3CN (40 ml) was photooxygenaied as above for 6 h. to give p-hydroxyhydroperoxide 19f (formula 19, RI = R2 = H, X - OMe) as indicated by TIC, To this reaction mixture was added p-toluenesulfonic acid (20 mg) and was left at room temperature overnight. Workup as above followed by chromatography on silica gel furnished 180 mg (19% yield based on the allylic alcohol 17f used) of 1,2,3-trioxane 27f. Hemisuccinate for trioxane 27f (compound 4If, formula 41, Rj = R2 = H, X = OMe) Hemisuccinate 41f was prepared from trioxane 27f in 80% yield following the procedure used for preparation of compound 4 la as given in example 5. Example 14 Ketoester llg (formula 11, R, = R2 = Me, X = OMe) A mixture of 4-hydroxy-3-methoxyacetophenone (15 g) ethyl 2-bromoisobutyrate (22 ml) and K2C03 (45 g) in acetone (450 ml) was refluxed for 27 h. Most of the solvent was distilled off and the reminder was diluted with water and extracted with ether, ether extract dried on Na2S04 and concentrated. The crude product was chromatographyed on silica gel (elution with 5% ethylacetate in hexane) to furnish 4.41 g (18% yield) of ketoester llg as an oil. β-Hydroxyester 13g (formula 13, R,, = R2 = Me, X = OMe) A mixture of ketoester llg (4.4 g), zinc (3 g) and ethyl bromoacetate (2.5 g) in benzene was refluxed for 7 hr. Work up as above to give 6.0 g of crude product which was used in the next step without purification. a,p-Unsaturated ester 15g (formula 15, R1 = R2 = Me, X= OMe) p-Hydroxyester 13g (crude product 6.0 g as obtained above) was dissolved in benzene (100 ml), I2 (40 ing) was added the reaction mixture was refluxed for 6 hr. Workup and purification effected as above furnished 2.7 g (49% yield, based on ketoester llg) of a,p-unsaturated ester 15g as an oil. Allylic alcohol 17g (formula 17, R, = R2 = Me ; X = OMe) α,β-Unsaturated ester 15g (1.9 g) was reduced with LiAlH4 (1.8 g) in dry ether at 0°C as above. Normal workup followed by chromatography furnished Llg (76% yield) of allylic alcohol 17g as an oil. Trioxane 27g (formula 27, R1 = R2 = Me ; X = OMe) A solution of allylic alcohol 17g (1.1 g) and methylene blue (20 mg) in acetonitrile (50 mi) was photooxygenated as above at 0°C for 7 h. to give p-hydroxyhy draper oxide 19g (formula 19, R, - R2 = Me, X = OMe) as indicated by TLC. The reaction mixture was divided into two equal parts. One part was reacted with 2-adamantanone (500 mg) in presence of cone. HC1 (4 drops) at room temperature overnight. Usual workup followed by chromatography furnished 300 ing (34% yield based 0:1 the alcohol 17g used) of trioxane 27g as thick oil. Example 15 Trioxane 23gl (formula 23, Rj = R2 = Me ; X = OMe ; R3, R, = -CH2CH2CH2CH2-) The other half of the reaction mixture as obtained in the above experiment was reacted with cyclopentanone (1 ml) in presence of cone. HC1 (5 drops) at r.t. overnight. Usual workup followed by purification furnished 210 mg (28% yield based on alcohol 17g) of trioxane 23gl. xample 16 Ketoester 12a (formula 12, R1 = R2 = H) A mixture of 3-hydroxyacetoplienone (5 g), ethyl chloroacetate (5.6 ml) and K2C03 (7.5 g) was heated at 65°C with stirring for 13 h. It was cooled to room temperature, diluted with water (50 ml) and extracted with ether (2 x 100 ml). Ether extract was washed with water (3 x 50 ml), dried (Na2SO4). concentrated and chromatographyed on silica gel using 50% ethylacetate - hexane as eluant to give 4.52 g (49% yield) of ketoester 12a as an oil. α,β-Unsaturated ester 16a (formula 16, Rt = R2 = H) To a refluxing mixture of ketoester 12a (15 g), zinc (6 g), iodine (70 mg) in benzene (350 ml) was added dropwise ethyl bromoacetaie (8 ml) and the reaction mixture was refluxed for 9 hr. Tlie reaction mixture was cooled, acidified with aqueous 10% HC1, benzene layer was separated and the aqueous layer was extracted with benzene. The combined benzene extract was washed with water, aqueous NaHC03, dried (Na2S04) and concentrated to give 14a which was dehydrated with P20 To a stirred and ice-cooled mixture of LiAlIi, (8 g) in dry ether (400 ml) was added dropwise a solution of a,p-unsaturated ester 16a (11 g) in dry ether and stirred the reaction mixture in ice bath for 6 h. It was quenched with H20 and 10% NaOH. The organic layer was separated and the residue was washed with ether. Hie combined ether extract was dried (Na2S04), concentrated and purified by column chromatography on silica gel using hexane - ethylacetate as eluant to give 5.8 g (74% yield) of allylic alcohol 18a. Trioxane 24al (formula 24, R1 = R2 = H ; R3, R4 = CH2CH2CH2CH2) A solution of allylic alcohol 18a (1.0 g) and Rose Bengal (5 mg) in acetonitrile (65 mg) was photooxygenaied at 0°C for 7 h. to give p-hydroxyhydroperoxide 20a (formula 20, R; := R2 ~ H) as indicated by TLC. To this reaction mixture were added cyclopentanone (1.5 ml) and p-toluenesulfonic acid (15 mg) and the reaction mixture was stirred at room temperature for 4 h. Workup as above followed by chromatography on silica gel column furnished 600 mg (43% yield based on allylic alcohol 18a) of trioxane 24al. Hemisacclnate of trioxane 24al (compound 38al, formula 38, R1 = R2 = H ; R3 = R4 = CH2CH2CH2CH2) A solution trioxane 24al (600 mg) and succinic anhydride (2.0 g) in pyridine (5 ml) was stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ether. The ether extract was washed with water, 10% aqueous HC1, water, dried (Na2S04) anc concentrated The crude product on purified by chromatography on silica gel using CH2C12 - ether as eluant furnished 780 mg (98% yield) of hemisuccinate 38al. Example 17 Trioxane 28a (formula 28, R1 = R2 = H) A solution of allylic alcohol 18a (1.0 g) and methylene blue (5 mg) in CH2C12 (65 mg) was photooxygenated as above at 0°C for 10 h. To the reaction mixture were added 2-adamantanone (1 g) and p-toluenesulfonic acid (15 mg) and the reaction mixture was kept at room temperature overnight. Usual workup as above followed by purification by chromatography on silica gel column furnished 350 mg (21% yield based en allylic alcohol 18a) of trioxane 28a as a thick oil. Hemisuccinate for trioxane 28a (compound 42a, formula 42, R1 = R2 = H) Hemisuccinate 42a was prepared in 91% yield by reacting trioxane 28a with succinic anhydride following procedure as given in the above example. Example 18 Ketoester 12b (formula 12, R! = R2 = Me) A mixture of 3-hydroxyacetophenone (5 g) ethyl 2-bromoisobutyrate (5.4 ml) and K2CO3 (7.5 g) was heated at 120°C for 6 h. The reaction mixture was diluted with water, extracted with ether. Ether extract was washed with water, dried, concentrated and chromatographyed on silica gel to furnish 1.82 g (22% yield) of ketoester 12b as an oil. α,β-Unsaturated ester 16b (formula 16, R1 = R2 = Me) To a refluxing mixture of ketoester 12b (14.6 g), zinc (7.3 g) and iodine (50 mg) in benzene (400 ml) was added dropvvise a solution of ethyl bromoacetate (7.3 ml) in benzene (50 ml) and the reaction mixture was refluxed for 14.5 hr. when it was cooled, acidified with 10% aqueous HCl. Benzene layer was separated, washed with aqueous NaHCO3, dried and concentrated to give -hydroxy ester 14b which was used in the next step without purification. The crude p-hydroxyester 14b as obtained above was disslved in benzene (500 nil), P205 (10 g) was added and the mixture was refluxed for 3 h. Usual workup followed by chromatography furnished α,β-unsaturated ester 16b (7 g, 42% yield based on 12b). Ailylic alcohol 18b (formula 18, Rt = R2 = Me) To a stirred and ice-cooled mixture of LiAlH4 (3.2 g) in dry ether (450 ml) was added a solution of unsaturated 16b (3.6 g). The reaction mixture was stirred for 2.5 h. in ice bath. It was quenched with water and 10% aqueous NaOH. Ether layer was .separated and concentrated to give 2.6 g of residue which was chromatographed on silica gel to give 2.3 g (86% yield) of allylic alcohol 18b. Trioxane 24bl (formula 24, R, = R2 = Me ; R3, R4 = CH2CH2CH2CH2) A mixture of allylic alcohol 18b (300 mg) and methylene blue (20 mg) in CH3CN (40 ml) was photooxygenated at 0°C for 5.5 h. to give p-hydroxyhydroperoxide 20b (formula 20, Rj = R2 = Me) as indicated by TLC. Tlie reaction mixture was divided in two equal parts. To one-half of this reraction were added cyclopentanone of (1 ml) and PTSA (40 mg) and the reaction mixture was stirred at room temperature for 5 h. Usual workup followed by chromatography on silica gel furnished 170 mg (81% yield based on alcohol 18b) of trioxane 24bl. Hemisuccinate for trioxane 24bl (compound 38bl, formula 38, RI = R2 = Me ; R3, R» = CH2CH2CH2CH2) To an ice-cooled solution of trioxane 24bl (200 mg) and succinc anhydride (400 mg) in CH2C12 (20 ml) were added Et3N (1 ml) and 4-climethylamino-pyridine (DMAP, 20 mg) and the reaction mixture was stirred at room temperature for 1.5 h. The solvent was removed under vacuum, acidified with 10% aq. HC1 and extracted with ether. Ether extract was washed with water, concentrated and purified by chromatography on silica gel to give 230 mg (92% yield) of compound 38bl as an oil. Trioxane 24b2 (formula 24, R, = R2 = Me, R3, R, = CH2CH2CH2CH2CH2) To the other half of the photooxygenated mixture obtained as in the above experiment were added cyclohexanone (1 ml) and PTSA (40 mg) and the reaction mixture was stirred at r.t. for 5 h. Workup and chromatography on silica gel column as above furnished 110 mg (50% yield based on alcohol 18b) of trioxane 24b2. Hemisuccinaie for trioxane 24b2 (compound 381)2, formula 38, Rj = R2 = Me ; R3, R* = CH2CH2CH2CH2 CH2) Trioxane 24b2 (250 mg) was reacted with succinc anhydride (350 nig) in CH2C12 (20 ml) as above and the crude product was purified by chromatography on silica gel using 25% ether in CH2C12 as eluant to give 280 mg (87% yield) of compound 38b2 as an oil. Example 19 Trioxane 28b (formula 28, Rj = R2 = Me) A solution of allylic alcohol 18b (300 mg) and methylene blue (70 mg) in CH3CN (30 ml) was photo oxygenated at -8°C for 6 h. To the reaction mixture were added 2-adamantanone (300 mg)'and p-toluenesulfonic acid (50 mg) and left at room temperature overnight. The solvent was removed under vacuum and the residue was diluted with aq. NaHC03 and water and extracted with ether. The ether -extract was washed with water, dried, concentrated and chromatographed on silica gel to furnish 310 mg (62% yield) of trioxane 28b as an oil. Hemisuccinate of trioxane 28b [compound 42b, formula 42, Rt = R2 = Me] To a stirred ice-cooled mixture of trioxane 28b (100 mg) and succinic anhydride (200 mg) in CH2C12 (10 ml) were added triethylamine (0.5 ml) and 4-dimethylamino pyridine (20 mg) and the reaction mixture was stirred at r.t. for 3 hr. The reaction mixture was concentrated under reduced pressure, acidified with 10% aquoeus HC1 and extracted with ether (2 x 20 ml). The ether extract was washed with water dried (Na2S04), concentrated and purified by column chromatography on silica gel to give 100 mg (80% yield) of hemisuccinate 42b as a thick oil. Example 20 Ketoester lie (formula 11, R1 = H, R2 = Me, X = H) A mixture of 4-hydroxyacetophenone (5 g), ethyl 2-brotnopropionate (5 ml) and K2CO3 (7.5 g) was heated at 120°C for 7.5 h. The reaction mixture was extracted with ether, washed with water, dried, concentrated and chromatographed on silica gel to furnish 1.8 g (21% yield) of lie, m.p. 64-72°C. ct,p-Unsaturated ester 15c (formula 15, Rt = H, R2 = Me, X = H) To a refluxing mixture of ketoester lie (25 g), Zn (6.5 g) and iodine (50 mg) in benzene (250 ml) was added dropwise ethyl bormoacetate (12 ml) and the reaction mixture was refluxed for 7 h. The crude product (13c) obtained after usual workup was dehydrated with iodine (2 g) in benzene (100 ml) by refluxing for 4 h. The reaction mixture was washed with a slution of sodium thiosulphate, concentrated and purified by chromatography on silica gel to give 14.6 g (47% yield) of 15c as an oil. Ailylic alcohol 17c (formula 17, Rt = H, R2 - Me, X = H) α,β-Unsaturated ester 15c (5.0 g) was reduced with LiAlH4 (3 g) in dry ether (250 ml) as above to give 2.7gallylic alcohol 17c. Trioxane 25c (formula 25, Rt = Me, R2 = X = H) A solution of allylic alcohol 17c (1.5 g) and methylene blue (10 mg) in CH2CN (45 ml) was photooxygenated as above for 6 h. to give p-hydroxyhydroperoxide 19c (formula 19, R, = Me ; R2 = X = H). One third (corresponding to 500 mg of lOc) was taken and reacted with norcomphor (1.0 g) in presence of catalytic amount of p-toluenesulfonic acid at r.t. for 3 h. Usual workup followed by chromatography on silica gel column furnished 300 mg (38% yield based on the allylic alcohol 17c used) of trioxane 25c. Example 21 Ketoester lid (formula 11, R1 = H, R2 = Et, X = H) A mixture of 4-hydroxyacetophenone (5.0 g), ethyl 2-bromobutyrate (5 ml) and K2CO3 (7.5 g) was heated at 120°C for 7.5 h. Workup followed by purification of the crude product as above (example 20) furnished 3.9 g (42% yield) of compound lid as an oil. α,β-Unsalm ated ester 15d (formula 15, R, = H, R2 = Et, X = H) To a refluxing mixture of ketoester lid (3.5 g), Zinc (2.0 g), iodine (50 mg) in benzene (50 ml) was added ethyl bormoacetate (1.5 ml) and the reaction mixture was refluxed for 5 h. It was acidified with 10% HC1, benzene layer was separated and concentrated and the crude product was purified by chromatography to give 2.45 g (52% yield) of 13d. Compound 13d (2.4 g) was dehydrated in refluxing benzene using P2Os as catalyst. Workup followed by column chromatography on silica gel as above furnished 2.0 g (88% yield) of ester 15d as an oil. Allylic alcohol 17d (formula 17, R, = H ; R2 = Et; X = H) a,p-Unsaturated ester 15d (2.7 g) was reduced with LiAlH, (1.5 g) in dry ether (150 ml) and the crude product was purified by chromatography on silica gel using hexane - ethylacetate as eluant to give 1.2 g of allylic alcohol 17d. Trioxane 27d (formula 27, R, = Et, R2 = X = H) A solution of allylic alcohol 17d (1.2 g) and methylene blue (10 mg) in CH3CN (40 ml) was photooxygenated as above for 7 h. to give p-hydroxyhydroperoxide 19d (formula 19, Rj = Et; R2 = X = H) as indicated by TLC. To one half of this reaction mixture were added adamantanone (600 mg) and PTSA (10 mg) and the reaction mixture was stirred at r.t. for 2 h. Usual workup followed by chromatography on. silica gel furnished 300 rag (30% yield based on the allylic alcohol 17d used) of trioxane 27d as oil. Example 22 Ketoester lie (formula 11, R, = H, R2 = n-pentyl, X = H) A mixture of 4-hydroxyacetophenone (5.0 g), ethyl 2-bromoheptanoale (8.3 g) and K2C03 was heated at 120°C for 7.5 h. The reaction mixture was extracted with ether. Ether extract was washed with water, dried, concentrated and chromatographed on silica gel to furnish 9.1 g (89% yield)xof compound lie, as an oil. α,β-Unsaturated ester 15e (formula 15, R1 = H, R2 = n-pentyl, X = H) To a refluxing mixture of ketoester lie (25 g), Zn (7.5 g), iodine (100 mg) in benzene (450 ml) was added ethyl bormoacetate (9 ml) dropwise and the resulting mixture was refluxed for 5.5 h. It was acidified with 10% HC1, benzene layer was separated, washed with aq. NaHC03 solution, dried and concentrated to give p-hydroxy-ester 13e which was used without purification in the next step. Crude product 13e as obtained above was dissolved in benzene (350 ml), iodine (100 mg) was added and the mixture was refluxed for 2.5 h. The reaction mixture was washed with a solution of sodium thiosulphate, dried, concentrated and chromatographed on silica gel (elution with 5% ethyl acetate -hexane) to give 22.1 g (71% yield) of a,p-unsaturated ester 15e as an oil. Allylic alcohol 17e (formula 17, R, = H ; R2 = n-pentyl; X = H) a,p-Unsaturated ester 15e (12 g) was reduced with LiAlll, (10 g) in dry ether (600 ml) at 0°C as above to give 8.3 g of crude product which was purified by chromatography on silica gel to furnish 6.5 g (71% yield) of allylic alcohol 17e. Trioxane 23el (formula 23, R, = CH2CH2CH2CH2CH3 ; R2 = X = H, R3, R4 = -CH2CH2CH2CH2-) A solution of alcohol 17e (2 g) and methylene blue (100 mg) in ~CH3CN (60 ml) was photooxygenated at 0°C for 4.5 h. to give p-hydroxyhydroperoxide 19e (formula 19, R, = CH^CHjCHjCEkCHs; R2 = X = H) as indicated by TLC. One half this photooxygenated reaction mixture was reacted with cyclopentanone (2 ml) in presence of PTSA(50 mg) atr.t. for 5.5 h. Usual workup and chromatography on silica gel column to furnish 610 mg (45% yield based on allylic alcohol 17e used) of trioxane 23el. Trioxane 27e (formula 27, Rt = CH2CH2CH2CH2CH3 ; R2 = X = H) To the other half of the photooxygenated mixture as obtained in the above example were added 2-adamantanone (1 g) and PTSA (50 mg) and the reaction mixuture wa stirred at r.t. for 5 h. Usual workup followed by chromatography on silica gel column using hexane - ethylacetate as eluant furnished 780 mg (76% yield based on allylic alcohol 17e used) of trioxane 27e as a thick oil. Hemisuccinate of trioxane 27e [compound 4le, formula 41, RI = H, R2 = n-pentyl: X = H] To a stirred and ice-cooled mixture of trioxane 27e (200 mg) and succinic anhydride (200 mg) in CH2C12 (20 ml) were added triethylamine (0.5 ml) and 4-dimethylamino pyridine (20 mg) and the reaction mixture was stirred at r.t. for 1.5 h. Workup as above followed by purification by column chromatography on silica gel fiirnished 200 mg (82% yield) of hemisuccinate 41eas a colourless oil. Using the above procedures the following liydroxy-functionaiized trioxane and their esters were also prepared. Trioxane 23a4 (formula 23, Rt = R2 = X = H ; R3, K, = Me, Et) ; 36% yield Trioxane 23aS (formula 23, R, - R2 = X = H, R3, R4 = Me, CH2CH2CH3); 43% yield Trioxane 23a6 (formula 23, R] = R2 = X = H, R3, R4 = Me, CH2CHMe2); 29% yield Trioxane 23a7 (formula 23, R = R2 = X = H, R3 = R = n-propyl); 21% yield Trioxane 23a8 (fonnula 23, R = R2 = X = H, R3 = R = n-butyl) ; 11% yield Trioxane 23a9 (fonnula 23, R, = R2 = X = H, R3 = R = n-pentyl); 16% yield Trioxane 23a10 (formula 23, R, = R2 = X = H, R3, R = -CH2(CH2)9-CH2-); 16% yield Trioxane 23all (formula 23, R = R2 = X = H, R3, R = -CH2-CH2-CO-CH2-CH2); 6% yield Trioxane 23al2 (fonnula 23, R - R2 - X = H, R3, R4 - H, -CeH5); 45% yield Trioxane 23al3 (formula 23, RI =R2 = X = H, R3,R= H, 1-naphthyl); 38% yield Trioxane 23b3 (formula 23, R! = R2 = Me, X = H, R3, R = H, 1-naphthyl); 7% yield Trioxane 23b4 (formula 23, R, = R2 = Me, X = H, R3, R4 = CH2(CH2)4-CH2); 15% yield Trioxane 23cl (formula 23, Rb R2 - H, Me ; X - H, R3, R4 = -CH2-CH2-CH2-CHr); 42% yield Trioxane 23c2 (formula 23, Rl5 R2 = H, Me ; X = H, R3, R4 = -CH2-(CH2)3-CH2); 46;% yield Trioxane 23dl (formula 23, R,, R2 = H, Et; X = H, R3, R, = -CHrCH2-CH2-CH2-); 33% yield Trioxane 23e2 (formula 23, R,, R2 = H, n-pentyl ; X = H, R3j R, = -CHr(CH2)rCH2); 54% yield Trioxane 23e3 (formula 23, R(, R2 - H, n-pentyl; X - H, R3, K, = -CH2-(CH2)4-CH2); 38% yield Trioxane 23e4 (fonnula 23, R^ R2 = H, n-pentyl; X - H, R3, R4 = -CH2-(CH2)3-CH2); 15% yield Trioxane 23e5 (formula 23, R,, R2 = H, n-pentyl; X = H, R3, R4 = Me); 54% yield Trioxane 23fl (formula 23, R! - R2 = H; X = OMe ; R3, R = -CH2-CPI2-CH2-CH2); 27% yield Trioxane 23f2 (formula 23, R! - R2 = H; X - OMe, R3, R4 = -CH2-(CH2) 3-CH2); 16% yield Trioxane 23gl (formula 23, R = R2 = Me ; X = OMe, R3, R4 = -CH2-CH2-CH2-CH2-); 28% yield Trioxane 24a2 (fonnula 24, R, - Rz = H; R3, R4 = -CH2(CH2CH2) ; 41% yield Trioxane 24a3 (fonnula 24; R, = R2 = H ; R3, 4 = -CH2(CH2)4-CH2) ; 60% yield Trioxane 24b3 (fonnula 24, R, = R2 - Me ; R3, R4 = H, 1-naphthyl); 24% yield Trioxane 25a (formula 25, Rs = R2 - H); 34% yield Trioxane 25c (fonnula 25, R,, R2 = H, Me); 39% yield Trioxane 25d (formula 25, R,, R2 - H, Et); 15% yield Trioxane 25e (formula 25, Rh R2 = H, n-pentyl); 35% yield Trioxane 26a (formula 26, R,, R2 = H); 23% yield Trioxane 26b (fonnula 26, Rb R2 = Me); 53% yield Trioxane 27c (fonnula 27, Rb R2 == H, Ms); 39% yield Trioxane 28b (formula 28, R,, R2 = Me); 27% yield Compound 31a2 (formula 31; R = R2 = X = H ; R3, R= -CH2-CH2-CHrCH2-; R5 - Et); 80% yield Compound 31a3 (fonnula 31 ; R, = R2 = X = H ; R3, R = -CH2-CH2-CH2-CH2-; R5 - n-Pr); 78% yield Compound 31a4 (formula 31; R, = R2 = X = H ; R3, R - -CH2-CH2-CH2-CH2- ; R3 = n-hexyl) ; 75% yield Compound 31a5 (formula 31; R, = R2 = X = H ; R3, R4 = -CH2-CH2-CH2-CH2- ; R5 = phenyl) ; 42% yield Compound 31a6 (formula 31; R! = R2 = X = H ; R3, R, = H, 1-naphthyl; R5 = CH3); 36% yield Compound 31bl (formula 31; R! - R2 = Me, X = H ; R3, R4 = H, 1-naphthyl; R, = CH3); 90% yield Compound 325)1 (formula 32 ; R, = R2 - Me ; R3, K = -CH2-CH2-CHrCH2-; R, = Me); 89% yield Compound 32b2 (formula 32; R! = R2 = Me ; R3, ^ = -CH2-(CH3)3-CH2-; R5 = Me); 86% yield Compound 32b3 (formula 32 ; R! = R2 - Me ; R3> R^ - H, 1-naphthyl; R5 = Me); 73% yield Compound 33al (formula 33 ; R, - R2 = X = H; R_, = Me); 82% yield Compound 33a2 (formula 33 ; R, = R2 = X = H; R5 = Et); 76% yield Compound 33a3 (formula 33 ; Rj = R2 = X = H; R, = n-hexyl); 83% yield Compound 34!) (formula 34 ; R! = R2 = Me, R5 = Me); 94% yield Compound 35b3 (formula 35 ; R, = R2 = Me ; X = H ; R5 - n-Pr) ; 57% yield Compound 35b5 (formula 35 ; R, = R2 - Me ; X = H; R5 = n-hexyl); 959/o yield Compound 36b (formula 36 ; R, - R2 - R5 = Me); 91% yield Compound 37al (formula 37 ; R, - R2 = X = H ; R3, R^ - -CH2-CH2-CH2-CH2-); 87% yield Compound 37a2 (formula 37 ; R, = R2 - X = H; R3, R4 = -CH2-(CH2)3-CH2-); 40% yield Compound 37a3 (formula 37; R, - R2 = X - II; R3 - R, = Me); 709-6 yield Compound 37a4 (formula 37 ; R, - R2 = X - H; R3 - R, - H, 1-naphthyl); 66% yield Compound 37b2 (formula 37 ; R, = R2 = Me, X = H; R3, R, = -CH2-(CH2)3-CH2-); 86% yield Compound 37b3 (formula 37 ; R = R2 = Me, X - H; R3, R, = H, 1-naphthyl): 66% yield Compound 37el (formula 37 ; R,, R2 = H, n-penthyl, X = H; R3, R - -CH2CH2CH2CH2-); 79% yield Compound 37fl (formula 37 ; R, - R2 - H, X - OMe ; R3, R4 = -CH2-CH2-CH2-CHr); 76% yield Compound 38a2 (formula 38 ; R, = R2 - H; R3, R = -CH2 (CH2) 3-CH2-); 90% yield Compound 38bl (formula 38 ; R, = R2 - Me; R3, R - -CH2-CH2-CH2-CH2-); 92% yield Compound 38b2 (formula 38 ; R - R2 - Me ; R3, R, = -CH2(CH2)3-CH2-); 88% yield Compound 38b3 (formula 38 ; R, = R2 = Me ; R3, R = H, 1-naphthyl); 87% yield Compound 39a (formula 39 ; R = R2 - X = H); 97% yield Compound 40b (formula 40 ; R, = R2 = Me); 96% yield Compound 41f (formula 41; R, = R2 = H; X = OMe); 80% yield Compound 41g (formula 41; R = R2 = Me, X = OMe) Compound 42a (formula 42 ; R1 = R2 = H); 91% yield Antimalarial Activity The antimalarial activity of the test compounds was evaluated in rodent using muitidrug resistant strain of Plasmodium yoelii Nigenensis in swiss mice. General Procedure : Random bred swiss mice of either sex (20 ± 2 gm) were inoculated intraperitoneally with 1 x 105 P. yoelii (MDR) parasites on day zero. The treatment with test compounds were administered to groups of 6 mice each at different dose levels ranging between 24-96 mg/kg/day. The trioxanes were dissolved in groundnut oil (or 50% sodium bicarbonate solutions in case of hemisuccinate derivatives) and were administered via intramuscular or oral route for 4 consecutive days (day 0-3). Blood smears from experimental mice were observed on day 4 and 7, day 10 and thereafter at regular interval till day 28 or death of the animal. The parasitaemia level on day 4 was compared with the vehicle control group and the percent suppression of parasitaemia in treated groups was calculated. For detenning the curative dose of a compound the treated mice were observed till day 28. The dose at which no parasitaemia develop during the observation period has been recorded as the curative dose. The aiitimalarial data is summarized in Table-4. Table 4 : Antimalarial activity of substituted trioxanes against multi drag resistant strain of Plasmodium yoelii Nigeriensis in svviss mice (Table Removed) Trioxane 27a, 271) ande their hemisuccinates 41a and 41b were evaluated for blood schizontocidal activity against Plasmodium. cynomolgi and Plasmodium knowlesi in Rhesus monkeys using the following protocol: For activity against P. cynomolgi, rhesus monkeys were inoculated intravenously with 1 x 105 parasitized RBC and the treatment was initiated when the parasitaemia level reached above 0.5%. For activity against P. knowlesi the rhesus monkeys were inoculated intravenously with 1 x 104 parasitized RBC and the treatment was initiated at 0.1% parasitaemia level. Compounds 27a and 27b were dissolved in groundnut oil and administered in various regimens for 3-5 days via oral or intramuscular (im) routes. Hemisuccinates 41a and 41b were dissolved in 5% bicarbonate solution and administered similarly by oral, im or iv routes. The blood smears from the treated monkeys were examined once daily to record parasitaemia clearance time and subsequent recurrence of parasitaemia. The animals in which no recrudescence was observed upto day 60 were recorded as cured. The antimalarial data is summerized in table 5 and table 6. Table 5 : Antimalarial activity of trioxanes against Plasmodium cynomolgi in rhesus monkey mode! (Table Removed) Table 6 : Antimalarial activity of trioxanes against P. hiowlesi in rhesus monkey model (Table Removed) Gametocytocidal .Activity Compounds 27a and 4la were also tested for gametocytocidal activity according to the following protocol: Different batches of 3 to 4 days old naive Anopheles stephensis mosquitoes are allowed to engorge blood from gametocyte carrying infected host (rhesus monkey infected with P, cynomolgi or hamster infected with P. yoelii') at different time intervals prior to and after administration with a single dose of the test compound. The blood fed mosquitoes were maintained for the next 7-10 days in an insectorium to allow development of oocysts. A comparison of mosquito infectively rate and oocyst numbers in pre-treatment versus post-treatment provided index for gametocytocidal potential of the test agent. Compound 27a and 4 la showed complete loss of infectivity in mosquito batches fed 24 h post-treatment with 50 mg/kg (im, single dose) in P. yoelii model and 20 mg/kg (im, single dose) or 30 mg/kg (oral, single dose) in P. cynomolgi model. We Claim 1. Novel substituted 1,2,4-trioxanes of formula 1 wherein R1, R2 are hydrogen, alkyl group such as methyl, ethyl, propyl; R3, R4 are hydrogen, alkyl group such as methyl, ethyl, aryl such as phenyS, naphthyl, R5 is hydrogen, alkyl group such as methyl, ethyl, propyl, aryl such as phenyl, or carboxyalkyl group such as CH2CH2C02H; Z is 0 or OCO. (Figure Removed)2. Novel trioxanes as claimed in claim 1 wherein the said compounds having structural formulae 23al-23al3, 23bl-23b3, 23el-23c2, 23d 1, 23el-23e5, 23fl-23f2, 23gl as shown below. (Figure Removed) 23al R1R2 23a2 R1,R2 23a3 R1, R2 23a4 R,,R2 23a5 23a6 23a7 R1,R2 23 a8 R1,K 23a9 R1R2 23alO R1R2 23all R1,R2 23al2 R1,R2 23al3 R1,R2 23bl R1,R2 H, H; X = H; R3, R4 = CH2CH2CH2CH2 H, H; X - H; R3, R4 = CH2CH2CH2CH2CH2 R2 = H, H; X = H; R3, R4 - Me, CH2CH2CH3 R2 = H, H; X = H; R3, R4= n-propyl, n-propyl R2 = H, H; X = H; R3, R4 = n-butyl. n-butyl R2 = H, H; X = H; R3, R4 = n-pentyl, n-pentyl : H, H; X - H; R3, R4 = -CH2-( CH2)9-CH2-: H, H; X = H ; R3, R4 = CH2CH2-CO- CH2CH2 - H, H ; X = H; R3, R4 - H, phenyl = H, H; X = H; R3, R4, = H, 1-naphthyl : Me, Me ; X = H; R3, R4 = CH2CH2CH2CH2 23b2 R1, R2 - Me, Me ; X = H; R3, R4 = CH2CH2CH2CH2CH3 23b3 R1, R2 - Me, Me ; X = H; R3, R4 = H, 1-naphthyl 23I»4 R1 , R2 = Me. Me ; X = H; R3 R4 = CH2-( C 23c 1 R1, R2 = H, Me ; X = H ; R3, R4 = CH2CH2CH2CH2 23c2 R1, R2 - H, Me ; X = H ; R3, R4 = CH2CH2CH2CH2CH2 23d 1 R1 , R2 = H, Et; X = H ; R3, R, = CH2CH2CH2CH2 23el R,, R2 = H, n-pentyl; X = H ; R3, R, = CH2CH2CH2CH2 23e2 R1, R2 = H,n-pentyl; X = H; R3, K, = CH2CH2CH2CH2CH2 23e3 R,, R2 = H, n-pentyl; X = H ; R3, R4 = - CH2(CH2)4CH2 23e4 R1, R2 = H, n-pentyl; X - H ; R3 R4 - - CH2(CH2)SCH2 23eS R1, R2 = H, n-pentyl; X = H; R3, R4 - Me, Me 23f2 R1, R2 = H, H ; X = OMe ; R3,R4 = CH2-(CH2)3-CH2 23gl R1, R2 = Me, Me ; X = OMe ; R3, R4 - CH2CH2CH2CH2 3. Novel trioxanes as claimed in claims 1 wherein the said compounds having the structural formulae 24al, 24bl, 24b3 as shown below. 24al R1,R2 = H, H;R3,R4: 24a2 R1, R2 = H, H; R3,R1, = CH2-(CH2)3-CH2 24a3 R1, R2 = H, H; R3, R4 = CH2-(CH2)4-CH2 24b 1 R1, R2 = Me, Me ; R3, R4 - CH2CH2CH2CH2 24b2 R1, R2 - Me, Me ; R3 R4 = CH2CH2CH2CH2CH2 24b3 R1, R2 - Me, Me ; R3, R4, = H, 1 -naphthyl 4. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural fonnulae 25a, 25c, 25d, 25e as shown below. 5. 25a R1;R2 = 25c Rl,R2 = 25d Rl,R2 = H,Et,X = H 25e R1, R2 = H, n-phenyl, X = H Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 26a, 26b as shown below. 6. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 27a, 27b, 27c, 27d, 27e, 27f, 27g as shown below. (Figure Removed) 27a R1,R2 27b R1,Rj 27c RbR2 27d R1,R2=H,Et;X = H 27e R1,R2 = H, n-pentyl; X = H 27f R1,R2=H,H;X = OMe 27g Rt,R2 = Me,Me;X=OMe 7. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural fonnulae 28a, 28b as shown below. (Figure Removed) Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural fonnulae 31al-31a6, 31bl as shown below. (Figure Removed) 31al R1, R2 = H, H; X = H; R3, R4 = CH2CH2CH2CH2; R5 = CH3 3 Ia2 R1, R2 - H, H; X - H; R3, R4 - CH2CH2CH2CH2; R5 = Et 31a3 R1 R2 = H, H; X - H; R3, R4 = CH2CH2CH2CH2; Rj - n-propyl 3Ia4 R1, R2 = H, H; X = H; R3, R4 = CH2CH2CfI2CH2; R, = n-hexyl 3 la5 R1, R3 = H, H; X = H; Ra, R4 = CH2CH2CH2CH2; R5 = Ph 3 Ia6 R1, R2 = H, H; X - H; R3, R4 - H, 1 -naphthyl; R, = CH3 3Ib 1 R1, R2 = Me, Me ; X = H; Rs, .R, = H, 1 -naphthyl; R, = Me 9. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 32bl-32b3 as shown below. 10. 32b 1 R1 R2 = Me, Me ; R3, R4 = CH2CH2CH2CH2; R5 = Me 32b2 R1, R2 = Me, Me ; R3, R, = CH2CH2CH2CH2CH2; R, = Me 32b3 R1, R2 = Me, Me ; R3, R4 = H, 1 -naphthyl; Rj = Me Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 33al-33a3 as shown below. 11 Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 34b as shown below. 12 (Figure Removed) Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 35al, 35bl-35b5 as shown below. 12. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 35al, 35bl-35b5 as shown below. (Figure Removed) 13. 3Sal R1,R2 35bl R1,R2 35b2 R1,R2 35b3 R1 R2 = Me, Me ; X = H; Ri = n-propyl 35b4 R1, R2 = Me, Me ; X = H; R3 = n-pentyl 3SbS R1 , R2 = Me, Me ; X = H; R, - n-hexyl Novel trioxanes as claimed in claim 1 wherein the said compounds having the structlirai foraralae 36b as shown below. (Figure Removed)14.36b Rj, R2 = Me, Me; R5 - Me Novel trioxanes as claimed in claim 1 wherein the said compounds having the.structural formulae 37al-37a4, 37bl-37b3, 37el, 37fl as shown below. 37al R1, R2 = H, H ; X = H; R3, R4 = CH2CH2CH2CH2 37a2 R1 , R2 = H, H; X = H; R3, R4 = CH2CH2CH2CH2CH2 37a3 R1,R2 = H,H;X = H;R3,R4 37a4 R1,R2 = H,H;X = H;R3,R4 = H, 1-naphthyl 37b 1 R1, R2 = Me, Me ; X = H; R3, R, = CH2CH2CH2CH2 37b2 R1, R2 = Me, Me ; X = H; R3, R4 = CH2CH2CH2CH2 37b3 R1 R2 = Me, Me ; X = H; R3, R4 = H, 1-naphthyl 37el R1, R2 - H, n-pentyl; X - H ; R3, R 37f 1 R1, R2 - H, H; X = OMe ; R3, ^ = CH2CH2CH2CH2 Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 38al-37a2, 38bl-38b3 as shown below. (Figure Removed)16.38al Ri, R2 - H, H; R3, R4 = CH2CH2CH2CH2 38a2 R!, R2 = H, H ; R3, R4 = CH2CH2CH2CH2CH2 38b 1 Rj, R2 = Me, Me ; R3, R4 - CH2CH2CH2CH2 38b2 Rlf R2 = Me, Me ; R3> R4 = CH2CH2CH2CH2CH2 38b3 RI, Rz = Me, Me ; R3, R, - H, 1-naphthyl Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 39a as shown below. (Figure Removed) 39a Rl,R2 = H,H;X = H 17. Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 40b as shown below. 1.8. Novel trioxanes as claimed in claim 1 whereta the said compounds having the structural formulas 4la, 4Ib, 41e, 4If, 41g as shown below. 19. 41a R1 = H,H;X = H 4II) R1 , R2 - Ms, Me ; X = II 4 le R1 I12 - K, n-penty!; X - H 4 If R1,R2 = H,H;X = OMe 41 g R1, R2 = Me, Me ; X = OMe Novel trioxanes as claimed in claim 1 wherein the said compounds having the structural formulae 42a, 421} as shown below. 20. 42a R1,R2=H,H 42b R1, R2=Me,Me A process for the preparation of novel substituted 1,2,4-trioxajies and their esters of general formula 1 which comprises reacting hydroxyacetopllenones of 2 wherein X represents hydrogen or lower alkoxy such as- OMe, with ct-haloesters of formula 3 wherein R, and R2 represent hydrogen, .alky! group such 35.methyl, ethyl, propyl and Yrepresnts halogen such as Cl or Br, la the presence of abase optionally in an organic solvent at a temperature in As range rauge of room temperature to refluxing'temperature to give keto-esters of general formula 4, wherein R1 R2 aad X have the sains meaning as above ; reacting keto-esters of general fonnula 4 'under Relormaisky condition in an aprotic organic solvent in the temperature range of room temperature to relaxing, temperature to give p-hydroxyesters of general fonnula S, wherein R1; R2 and X have the same meaning as above ; dehydrating p-hydroxyestsrs of formula 5 using a catalyst in an organic solvent at a temperature in the range of room temperature to refiuxmg temperature to give α-β-unsaturat5d esters of general formula 6, wherein R1,R2 and X have (he same meaning as above ; reducing α,β-wisawrated esters of general formula 6 with a complex metal hydride such as LiAlH4 in an ether solvent at a temperature in the range of 0°C to room temperature to give alSylie alcohols of fonnula 7 wherein R1 R2, X have the same meaning as above; oxygenation of allylic alcohols of formula 7 in presence of a sensitizer in an organic solvent at a temperature in the range of -IO°C to room temperature to give p-hydrcxyhydroperoxides of general formula 8 wherein R., R2, X hove the same meaning above ; isolating and then reacting or reacting in situ p-hydroxyhydroperoxides of fonnula S with compounds containing aldehyde or ketone group in presence of an acid catalyst in an organic solvent at a. temperature in the range of 0°C to room temperature to give hydroxy-fcciionalized 1,2,4-trioxaaes of general fonnula 1, wherein R, R2 and X have the same meaning as above, R3, R4 are hydrogen, alley! group such as methyl, propyl, aryl group such as phenyl, naphthyl or part of a cyclic system, R.5 is K ajid Z is 0 ; reacting hydroxy-iiinctionalizedtrioxanss of general fonnula 1, wherein R is H and Z is O with an acid chloride or anhydrides in presence of a base in. an organic solvent at a temperature in the-range of 0°C to room temperature to give trioxane esters of genera! fonnula 1, wherein RI, R?, R3, R4 and X have the same meaning as above, R5 is alkyl group such as methyl, ethyl, propyS, aryl such CO. 21. A process as claimed in claim 20, wherein the substituted acetophenones of formula 2 are reacted with a-halosstsrs of fonnula 3 in presence of a base such as KaHC03, Na2C03, K2C03, in an organic solvent such as acetone, DMSO, DMF. 22. A process as claimed in claims 20-21 wherein Reformaisky reaction is carried out by reacting ketoesters of fonnula 4 with ethyl bromoacetate and Zn in an aprotic organic solvent such benzene, di ethyl ether, THK 23. A process as claimed in claims 20-22 wherein dehydration of p-hydroxyesters of formula 5 is effected in a hydrocarbon solvent such as benzene, toluene, CH2C12, using a catalyst such as k, P2O5, p-toluene-sulfbrnic acid, acidic resin such as Amberlyst-15. 24. A process as claimed in claims 20-23 wherein the reduction of esters of formula 6 with LiAlILj is carried out in an ether solvent such as diethyl ether, THF. 25. A process as claimed in claims 20-24 wherein, the oxygenation is effected by photooxygenation of allylic alcohols of formula 7 in an organic solvent such as acetone, CH3CN, CH2C13, methanol, ethanol, using a dye (sensitizer) such as methylene blue, Rose Bengal, tetraphenyl porphine. 26. A process as claimed in claims 20-25, wherein condensation of p-hydroxyhydroperoxides of formula 8 with aldehydes and ketones of formulae 21-22 is done in an organic solvent such is CH2C12, CHC13, benzene, CH3CN, using as acid catalyst, such as HC1, H2S04, p-toluenr sulfonic acid, BF3.OEt2, acedic resin such as Amberlyst-15. 27. A process as claimed in claims 20-26, wherein esterification of faydroxy-functionaiized trioxanes of formulae 23-28 with acid chlorides of formula 29 or an acid anhydride of formula 30 is done in an organic solvent such as CH2C12, CHC13, THF, CH3CN in presence of base such as Et3N, pyridine, dimethylaminopyridine. 28. A process as claimed in claims 20-27, wherein hemisuccinate derivatives of formulae 37-42 are prepared in an organic solvent such as CH2C12, CHC13, CH3CN, toluene, THF, in presence of a base such as Et3N, pyridine, dimethylaminopyridine. 29. A process as claimed in claims 20-28, wherein the compounds containing aldehyde and ketom'c group are of formulae 21-22 given in the drawing wherein R3 and R« are hydrogen, alky! group such as methyl, ethyl, aryl such as phenyl, naphthyl, araalkyl such as benzyl, or part of a cyclic system. 30. A process as claimed in claims 20-29, wherein acid chlorides and acid anhydrides used are having the formulae 29 and 30 wherein R5 represent alkyl group such as methyl, ethyl, propyl, aryl such as phenyl. 31. A process for the preparation of novel substituted 1,2,4-trioxanes and their esters substantially as herein described with reference to the examples and the drawings accompanying this specification.

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