A Novel Enantioselective Alkylation and Its Application to the Synthesis of an Anticancer Agent.

Abstract

Enantioselective syntheses Enantioselective syntheses O 0031 A Novel Enantioselective Alkylation and Its Application to the Synthesis of anAnticancer Agent. -Title investigation is presented in connection with studies on an efficient synthesis of the potent farnesyl protein transferase inhibitor lonafarnib (VI). A unique water effect on enantioselectivity and yield is observed for all alkylation reactions investigated. Other additives, e.g. LiOH, B(OH)3, MeOH or AcOH are mentioned to have no beneficial effects [most yields not given]. -(KUO, S.-C.; CHEN, F.; HOU, D.; KIM-MEADE, A.; BERNARD, C.; LIU, J.; LEVY, S.; WU*, G. G.; J. Org. Chem. 68 (2003) 12, 4984-4987; Chem. Process Dev., Schering-Plough Res. Inst., Union, NJ 07083, USA; Eng.) -Nuesgen 40-039

Organolithium Reagents in Pharmaceutical Asymmetric Processes

“…Chemists at Schering-Plough discovered a novel enantioselective alkylation of doubly benzylic substrates with secondary electrophiles and applied it to the synthesis of Lonafarnib, an anticancer agent . As shown in Scheme , the desired chiral center in Lonafarnib was established via an alkylation of the doubly benzylic carbon in 65 with a secondary electrophile of the piperidine derivative.…”