203923-89-1Relevant articles and documents
Methods for the total chemical synthesis of enantiomerically-pure 7-(2′-trimethylsilyl)ethyl camptothecin
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, (2014/05/20)
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.
Copper-free Sonogashira reaction using 7-chloro camptothecins
Luo, Yu,Gao, Heyong,Li, Yunfei,Huang, Weigang,Lu, Wei,Zhang, Zhaoguo
, p. 2465 - 2470 (2007/10/03)
We studied copper-free Sonogashira reaction using 7-chloro camptothecins, and determined that rac-BINAP/Pd(OAc)2 was an efficient catalyst for the coupling reaction. With this process, a number of 7-substituted camptothecins with a wide range of functional groups are potentially accessible. Besides, two drugs, SN-38 and BNP-1350, could be prepared by this method.
PROCESS FOR MAKING CAMPTOTHECIN DERIVATIVES
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Page/Page column 8-11, (2010/02/12)
A process for synthesizing highly lipophilic derivatives of camptothecin. The process includes reacting dissolved, underivatized camptothecin with a silylated heterocyclic compound in a modified Minisci-type alkylation reaction to produce 7-substituted derivatives of camptothecin.