Chromium-mediated coupling and application to the synthesis of halichondrins
US10344038B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Apr 29, 2016 |
| Grant date | Jul 9, 2019 |
| Priority date | — |
| Expiry date | Apr 29, 2036 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D493/14
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.