Taxane compounds, compositions and methods
The present invention provides a method for the preparation of orally available pentacyclic taxane compounds, as well as intermediates useful in their preparation.
1. A method of making a compound, comprising coupling a taxane side chain precursor compound to a C-13 hydroxyl group of a compound of formula I
to produce a protected taxane reaction product, or a salt thereof.
2. A compound having a structure of formula (II)
wherein Me is methyl and BOC is tert-butoxycarbonyl.
3. A compound having a structure of formula (III)
wherein BOC is tert-butoxycarbonyl and R 33 is a protected hydroxyl group.
4. A method of synthesizing the compound of claim 3 , comprising coupling a taxane side chain precursor compound having a formula
wherein R 2 is an alkoxy group having from 1 to 6 carbon atoms or a halogen atom and R 33 is a protected hydroxyl group to a C13 hydroxyl group of a compound having a structure of formula (I)
to produce a protected taxane reaction product having a structure of formula (III).
5. The method of claim 4 , wherein the C13 hydroxyl group is protected by a triisopropylsilyl (TIPS) or 2-methoxy propyl (MOP) group.
6. The method of claim 5 , wherein R 2 is fluorine.
7. The method of claim 6 , wherein fluorine is at the 3-position of pyridine.
8. The method of claim 4 , wherein the side chain precursor compound has a formula
wherein Me is methyl and BOC is tert-butoxycarbonyl.
9. A method of functionalizing a vinyl acetal, comprising: providing a compound having a structure of the formula
and oxidatively cleaving the terminal olefin group to form an aldehyde having the formula
10. The method of claim 9 , further comprising reductively aminating the aldehyde to provide a compound having the formula
and hydrogenating the C6-C7 double bond.
11. A method of functionalizing a vinyl acetal, comprising:
providing a compound having the formula
and oxidatively cleaving the terminal olefin group to form an aldehyde having a structure of the formula
12. The method of claim 11 , further comprising reductively aminating the aldehyde.