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AssigneeCouncil of Scientific and Industrial Research
InventorsSunil Kumar Chattopadhyay, Ram Prakash Sharma, Sushil Kumar, Kunnath Padmanabhan Madhusudanan
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A process has been developed for production of taxols A, B, C with high yields from 7-xylosyl-10-deacetyl taxol A (taxol analogue A or, xyloside A), 7-xylosyl-10-deacetyl-taxol B (taxol analogue B or xyloside B), 7-xylosyl-10-deacetyl--taxol C (taxol analogue C or xyloside C), which comprises (i) isolating the taxol analogues A, B, C form the stembark of Taxus wallichiana by an improved process devoiding of solvent partitioning step, (ii) treating the isolated taxol analogues A, B, C with periodates in an acid free polar solvent medium to cleave the diol into dialdehyde at ambient temperature, (iii) reducing the dialdehyde solution with borohydride in a polar solvent--acetic acid medium at 0.degree.-40.degree. C. into an acetal, (iv) acidifying the resultant acetal with a mixture of mineral acid-polar solvent at 0.degree.-40.degree. C. into intermediate product 10-deacetyl taxols A, B, C, (V) reacting 10-deacetyl taxols A or B or C with a silane in presence of a base at 20.degree.-40.degree. C. to protect 2', 7-hydroxyl groups, of 10-deacetyl taxols A, B, C (vi) acetylating the 10-hydroxyl group in situ with an acetylating agent at 10.degree.-40.degree. C., (vii) deprotecting the 2', 7-hydroxyl groups with a mixture of mineral acid-polar solvent at 0.degree.-10.degree. C. (viii) isolating taxols A or B or C by chromatography over silica.
A process for the production of taxol A, B, C of the formula (3) ##STR4## Where R represents C.sub.6 H.sub.5 (taxol A) or CH.sub.3 C=CH CH.sub.3 (taxol B) or, C.sub.5 H.sub.11 (taxol C) which comprises isolating the taxol analogues .sup.7 -xylosyl-10-deacetyl taxols A, B, C of the formula (1), ##STR5## where R represents C.sub.6 H.sub.5 (taxol analogue A or xyloside A), or CH.sub.3 C=CH CH.sub.3 (taxol analogue B or xyloside B) or C.sub.5 H.sub.11 (taxol analogue C or xyloside C) from the stem bark of Taxus wallichiana (a) by extracting the air dried, pulverized stem bark with alcohols at ambient temperature, (b) evaporating the solvent to obtain a residue, (c) stirring the residue with water to obtain a thick precipitate, (d) isolating the analogues 7-xylosyl-10-deacetyl taxols A, B, C from the precipitate obtained by flash chromatography over a bed of silica, (e) dissolving the isolated analogue in polar solvent, (f) reacting the resultant solution with periodates at 20.degree.-40.degree. C. for 20-40 hours to cleave the diol system of the xyloside into dialdehyde, (g) reducing the dialdehyde solution with borohydrides at 0.degree.-40.degree. C. in a polar-solvent acetic acid mixture, (h) acidifying the resultant acetal with a mineral acid in a chlorinated solvent at 0.degree.-40.degree. C. for 2-4 hours to 10-deacetyl taxols A, B, C of the formula (2) ##STR6## where R represents C.sub.6 H.sub.5 (10-deacetyl taxol A) or CH.sub.3 C=CH CH.sub.3 (10-deacetyl taxol B) or C.sub.5 H.sub.11 (10-deacetyl taxol C), (i) treating the resultant 10-deacetyl taxols A, B, C with specific silanes selected from (chlorotriethyl silane, chloro triisobutyl silane, chlorotriisopropyl silane, and chloro trimethyl silane) at a specific temperature of 10.degree.-40.degree. C. for a period of 20-40 hours to block the 2', 7-hydroxyl groups of lo-deacetyl taxols A, B, C;
A process as claimed in claim (1) wherein the polar solvents used in dissolving the taxol analogue 7-xylosyl-10-deacetyl taxols A, B, C, in the mixture of polar solvent and acetic acid to dissolve the dialdehyde for barohydride reduction, and in the mixture of polar solvent and mineral acid mixture to deprotect the 2', 7-hydroxyl groups, are selected from methanol, ethanol, propanol, butanol.
Dependencies are inferred from the claim text.