Microbial transformation method for the preparation of an epothilone

A method for the preparation of at least one hydroxyalkyl-bearing compound of the following formula III:

• where
• Q is selected from the group consisting of
• G1 is the following formula V
• HO—CH2—(A1)n—(Q1)m—(A2)o (V),
• where
• A1 and A2 are independently selected from the group of optionally substituted C1-C3 alkyl and alkenyl;
• Q1 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 O and H, OR7;
• M is O, S, NR8, or CR9R10;
• B1 and B2 are selected from the group consisting of OR11, and OCOR12;
• R1-R5 and R12-R17are selected from the group consisting of H, alkyl, substituted alkyl, aryl, and heterocyclo, and wherein 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, trialkylsily, alkyldiarylsilyl, and dialkylarylsilyl;
• R8 is selected from the group consisting of H, alkyl, substituted alkyl, R13C═O, R14OC═O and R15SO2;
• 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 contacting at least one compound of the following formula IV:
• where
• Q, W, X, M, B1, B2, and R1-R17 are as defined above;
• G2 is the following formula VI
• CH3—(A1)n—(Q1)m—(A2)o (VI),
• where A1, Q1, A2, n, m, and o are defined as above;
• the pharmaceutically acceptable salts thereof and any hydrates,solvates, or geometric, optical and stereoisomers thereof;
• with a microorganism, or P-450 enzyme isolated therefrom, said microorganism or P-450 enzyme capable of selectively catalyzing the hydroxylation of G2 to G1 and effecting said hydroxylation.