Process for the preparation of combretastatins
US6759555B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Apr 9, 2003 |
| Grant date | Jul 6, 2004 |
| Priority date | — |
| Expiry date | Apr 9, 2023 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY02P20/55
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present invention provides novel processes for the preparation of combretastatins or stilbene compounds of formulae (I) and (III) wherein A is NH2 or and PG is a protecting group.The disclosed and claimed processes include (1) Wittig condensation between a nitromethoxybenzaldehyde and a trimethoxybenzylphosphonium salt or between a trimethoxybenzaldehyde and a nitromethoxybenzylphosphonium salt to provide an intermediate compound of formula (I) wherein A is NO2, and subsequent iron powder reduction to provide a compound of formula (I) wherein A is NH2; (2) Wittig condensation of the same precursor aldehydes and phosphonium salts wherein NO2 is replaced by NH2 to provide a compound of formula (I) wherein A is NH2; and (3) a process for condensation of a compound of formula (I) wherein A is NH2 with a doubly protected serinamide to provide an intermediate of formula (III), and subsequent hydrolysis to provide a compound of formula (I) wherein A is —NH—C(═O)CH(NH2)CH2OH, or the pharmaceutically acceptable salts thereof. Also claimed is a compound of formula (III).
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.