Patent ID: 6727369
Filing Date: 2004-04-27
Classification: C07D

Abstract:
A process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having the formula: wherein R2 is hydroxy or â€”OCOR31; R4a is hydroxy or â€”OCOR30, provided, however, that when R2 is benzoyloxy, R4a is other than acetoxy; R6 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R6a forms an oxo; R6a is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R6 forms an oxo; R7 is hydrogen or together with R7a forms an oxo; R7a is hydrogen, halogen, protected hydroxy, â€”OCOR29, hydroxy, or together with R7 forms an oxo; R9 is hydrogen; R9a is hydrogen, hydroxy, protected hydroxy, or â€”OCOR29; R10 is hydrogen or together with R10a forms an oxo; R10a is hydrogen, hydroxy, protected hydroxy, â€”OCOR29, or together with R10 forms an oxo; R13 is hydroxy or protected hydroxy; R14 is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; R14a is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R1 forms a carbonate; and R29, R30 and R31 are independently hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl; the process comprising selectively reducing a C2 benzoate substituent and/or a C4 acetate substituent of a derivative or analog of baccatin III or 10-desacetyl baccatin III with an aluminum hydride, a borohydride or a tetraalkylammonium salt to a corresponding C2 hydroxy substituent and/or C4 hydroxy substituent, and acylating the C2 hydroxy substituent and/or the C4 hydroxy substituent to convert the C2 hydroxy substituent to R31COOâ€” and/or convert the C4 hydroxy substituent to R30COOâ€” wherein R31 and R30 are as defined above.