Methods for the total chemical synthesis of enantiomerically-pure 7-(2′-trimethylsilyl)ethyl camptothecin
US8722886B1 · kind B1 · utility
Assignee
Inventors
Key dates
| Filing date | Nov 13, 2012 |
| Grant date | May 13, 2014 |
| Priority date | — |
| Expiry date | Nov 13, 2032 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07F7/0812
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present invention discloses and claims five (5) novel, highly efficient synthetic routes for the total synthesis of enantiomerically-pure (i.e., 99%) 7-(2′-trimethylsilyl)ethyl camptothecin (BNP1350; Karenitecin; Cositecan). These aforementioned synthetic schemes are the first to disclose the total syntheses of 7-(2′-trimethylsilyl)ethyl camptothecin using a highly novel direct, non-linear and convergent synthetic strategy which involves annealing the key C7-(trimethylsilyl)ethyl side chain-bearing A ring key synthons to an enantiomerically-pure tricyclic pyridone; rather than through the conventional methodology which incorporates the C7-(trimethylsilyl)ethyl side chain as the final synthetic step on a totally synthesized camptothecin parent compound. The current novel synthetic approaches reported herein since utilize desirably functionalized A-ring with preinstalled trimethyl silyl ethyl side chain, the aforementioned synthetic methodologies have a wider scope of making wide range of pharmaceutically relevant A-ring substituted BNP1350 analogs by substituting desirably functionalized nitro or protected amino phenyl carboxy A-ring as the starting material.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.