Synthesis of epothilones

A method of connecting epothilone precursors comprising the steps of:

• providing a first epothilone precursor of the formula
• 25
• where n2 is an integer from 1-4, and R3 is selected from the group consisting of H, C1-C10 straight and branched chain all groups, substituted and unsubstituted benzyl groups, and C1-C10 alkoxy groups;
• providing a second epothilone moiety of the formula
• 26
• where n1 is an integer from 0-4, R4 is selected from the group consisting of H, C1-C10 straight and branched chain alkyl groups, substituted and unsubstituted benzyl groups, and C1-C10 alkoxy groups, R5 and R6 are each individually and respectively selected from the group consisting of H, substituted and unsubstituted aryl and heterocyclic groups, C1-C10 straight and branched chain alkyl groups, and substituted and unsubstituted benzyl groups, R7 is H, or straight or branched chain C1-C C10 alkyl groups, and P′ is a protecting group, comprising the steps of:
• reacting said second epothilone precursor with a base to form an enolate;
• and.
• reacting said enolate with said first epothilone precusor.

A method of synthesizing a vinyl halide epothilone precursor having the formula

• 27
• where n3 is an integer from 1-4, R is selected from the group consisting of C4-C8 cycloalkyl, and substituted and unsubstituted aromatic and heteroaromatic groups, R1 and R2, are each individually and respectively selected from the group consisting of H, C1-C10 straight and branched chain alkyl groups, substituted and unsubstituted benzyl groups, and C1-C10 alkoxy groups, P′ is a protecting group, and M is either bromine or iodine, comprising the steps of:
• providing an alkynyl ketone of the formula
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• wherein n3, M and R2 are as previously defined;
• asymmetrically reducing said alkynyl ketone to create the alcohol form of the alkynyl ketone;
• reacting said alcohol form with a reagent system selected from the group consisting of (R1)3Al and zirconocene dichloride or stannyl cupration reagent and R1-halide to form a vinyl metal species;
• reacting said vinyl metal species with an aryl or vinyl halide to form an allyl alcohol;
• and
• converting said allyl alcohol to said halide epothilone precursor.