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US 8,410,305 B2Granted
Intermediates and methods for the preparation of epothilones
AssigneeKosan Biosciences, Inc.
InventorsYue Chen, Yong Li
Life of this patent
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Abstract
Highly efficient methods are provided for preparing key intermediates in the synthesis of epothilones and use new alane reagents which are broadly applicable and can provide selected components having a variety of substituents groups.
Claims4
A method for the preparation of an epothilone intermediate, said method comprising:
- a) contacting a compound having the formula:
- wherein the subscripts n and m are each independently 0 or 1, indicating the absence or presence of methyl groups at the respective positions;
- X1 is a member selected from the group consisting of OR1, N(R2)2 and N(R2)OR1;
- wherein R1 is selected from the group consisting of H, lower alkyl, a carboxylic acid protecting group and a hydroxy protecting group, and each R2 is independently selected from the group consisting of H, lower alkyl and an amino protecting group;
- Y1 is a member selected from the group consisting of O and NR4, wherein R4 is selected from the group consisting of H, lower alkyl and an amino protecting group;
- with an alane reagent having the formula:
- wherein each Ra is independently selected from lower alkyl and cycloalkyl;
- R is a member selected from the group consisting of vinyl, allyl, 2-buten-1-yl and 3-trimethylsilylprop-2-yn-1-yl;
- and
- Z is a member selected from the group consisting of CH3 and CF3;
- to provide a compound having the formula:
- wherein the subscripts n and m are each independently 0 or 1, indicating the absence or presence of methyl groups at the respective positions;
- X is a member selected from the group consisting of CH3, OR1, N(R2)2 and N(R2)OR1;
- wherein R1 is selected from the group consisting of H, lower alkyl, a carboxylic acid protecting group and a hydroxy protecting group, and each R2 is independently selected from the group consisting of H, lower alkyl and an amino protecting group;
- Y is a member selected from the group consisting of OR3 and NHR4, wherein R3 is selected from the group consisting of H, lower alkyl and a hydroxy protecting group, and R4 is selected from the group consisting of H, lower alkyl and an amino protecting group;
- Z is a member selected from the group consisting of CH3 and CF3;
- and
- R is selected from the group consisting of vinyl, allyl, 2-buten-1-yl and 3-trimethylsilylprop-2-yn-1-yl.
15 more elements
Dependencies are inferred from the claim text.