Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor

Michael E. Pierce, Rodney L. Parsons, Lilian A. Radesca, Young S. Lo, Stuart Silverman, James R. Moore, Qamrul Islam, Anusuya Choudhury, Joseph M.D. Fortunak, Dieu Nguyen, Chi Luo, Susan J. Morgan, Wayne P. Davis, Pat N. Confalone, Cheng Yi Chen, Richard D. Tillyer, Lisa Frey, Lushi Tan, Feng Xu, Dalian ZhaoAndrew S. Thompson, Edward G. Corley, Edward J.J. Grabowski, Robert Reamer, Paul J. Reider

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.

Original languageEnglish (US)
Pages (from-to)8536-8543
Number of pages8
JournalJournal of Organic Chemistry
Volume63
Issue number23
DOIs
StatePublished - Nov 13 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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    Pierce, M. E., Parsons, R. L., Radesca, L. A., Lo, Y. S., Silverman, S., Moore, J. R., Islam, Q., Choudhury, A., Fortunak, J. M. D., Nguyen, D., Luo, C., Morgan, S. J., Davis, W. P., Confalone, P. N., Chen, C. Y., Tillyer, R. D., Frey, L., Tan, L., Xu, F., ... Reider, P. J. (1998). Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor. Journal of Organic Chemistry, 63(23), 8536-8543. https://doi.org/10.1021/jo981170l