Synthesis of fr901464 and analogs with antitumor activity

A method for treating a cellular proliferative disorder in a patient, comprising administering to the patient a therapeutically effective amount of a compound having Formula I, or a pharmaceutically acceptable ester thereof:

• wherein
• R1 and R8 are independently selected from the group consisting of H, C1-6-alkyl, halo(C1-6-alkyl), C(O)R11, C(O)OR11, and C(O)NR12R13,
• wherein each R11 is independently H, C1-6-alkyl, or halo(C1-6-alkyl), and
• wherein R12 and R13 are selected independently from the group consisting of H, C1-6-alkyl, and halo(C1-6-alkyl);
• or R12 and R13, together with the nitrogen atom to which they are bound, form a 5- to 6-membered heterocyclic or heteroaromatic ring;
• R2, R3, R4, R5, and R6 are independently selected from the group consisting of H, C1-6-alkyl, and halo(C1-6-alkyl);
• R7 is selected from the group consisting of H, C1-6-alkyl and halo(C1-6-alkyl);
• and
• R9 and R10 are independently selected from the group consisting of H, C1-6-alkyl, and C1-6-alkyl substituted with one to three groups independently selected from halo, hydroxy, and C1-6-alkoxy;
• R14 and R15 are selected independently from the group consisting of halo(C1-6-alkyl), C(O)R11, F, Cl, NO2, and B(OR11)2, wherein R11 is as defined above;
• or R14 and R15, together with the carbon atom to which they are bound, form an epoxide ring;
• provided that when R1 is C(O)CH3, R2, R4, and R8 are hydrogen, and R3, R5, R6, R7, and R9 are methyl, then R10 is not hydrogen or OH.