Microbial transformation method for the preparation of an epothilone

A method for the preparation of at least one 26-hydroxyepothilone of formula:

• 7
• where:
• Q′ is selected from the group consisting of
• 8
• G2 is the following formula (VI)
• CH3-(A1)n-(Qa)m-(A2)o- (VI)
• A1 and A2 are independently selected from the group of optionally-substituted (C1-C3)alkylene and (C2-C3)alkenylene;
• Qa is an optionally-substituted ring system containing one to three rings and at least one carbon to carbon double bond in at least one ring;
• n, m, and o are integers independently selected from the group consisting of zero and 1, where at least one of m or n or o is 1;
• W is O or NR6;
• X is selected from the group consisting of 0, and H, OR7;
• M is O, S, NR8, or CR9R10;
• B1 and B2 are selected from the group consisting of —OR11 and —OC(═O)R12;
• R1-R4 and R12—R17 are selected from the group consisting of H, alkyl, substituted alkyl, aryl, and heterocyclo, except R15 is not hydrogen, and when R1 and R2 are alkyl, they can be joined to form a cycloalkyl;
• R6 is selected from the group consisting of H, alkyl, and substituted alkyl;
• R7 and R11 are selected from the group consisting of H, alkyl, substituted alkyl, trialkylsilyl, alkyldiarylsilyl, and dialkylarylsilyl;
• R8 is selected from the group consisting of H, alkyl, substituted alkyl, R13C(═O)—, R14OC(═O)—, and R15S(O)2—;
• and
• R9 and R10 are selected from the group consisting of H, halogen, alkyl, substituted alkyl, aryl, heterocyclo, hydroxy, R16C(═O)—, and R17OC(═O)—;
• the pharmaceutically-acceptable salts thereof and any hydrates, solvates, or geometric, optical and stereoisomers thereof;
• comprising the steps of:
• a) contacting at least one epothilone of formula IVa
• 9
• where:
• 10
• the pharmaceutically-acceptable salts thereof and any hydrates, solvates, or geometric, optical and stereoisomers thereof;
• with a microorganism or enzyme derived therefrom capable of selectively catalyzing the hydroxylation of said R5 group to —CH2OH;
• and
• b) effecting said hydroxylation.