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 Zhao; Andrew S. Thompson; Edward G. Corley; Edward J.J. Grabowski; Robert Reamer; Paul J. Reider

doi:10.1021/jo981170l

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 Zhao

Andrew S. Thompson, Edward G. Corley, Edward J.J. Grabowski, Robert Reamer, Paul J. Reider

Research output: Contribution to journal › Article › peer-review

235 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 language	English (US)
Pages (from-to)	8536-8543
Number of pages	8
Journal	Journal of Organic Chemistry
Volume	63
Issue number	23
DOIs	https://doi.org/10.1021/jo981170l
State	Published - Nov 13 1998
Externally published	Yes

All Science Journal Classification (ASJC) codes

Organic Chemistry

Access to Document

10.1021/jo981170l

Cite this

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

@article{757dd7e66d79472cb22ba33319f0cfec,

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

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.",

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

year = "1998",

month = nov,

day = "13",

doi = "10.1021/jo981170l",

language = "English (US)",

volume = "63",

pages = "8536--8543",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

number = "23",

}

Pierce, ME, Parsons, RL, Radesca, LA, Lo, YS, Silverman, S, Moore, JR, Islam, Q, Choudhury, A, Fortunak, JMD, Nguyen, D, Luo, C, Morgan, SJ, Davis, WP, Confalone, PN, Chen, CY, Tillyer, RD, Frey, L, Tan, L, Xu, F, Zhao, D, Thompson, AS, Corley, EG, Grabowski, EJJ, Reamer, R & Reider, PJ 1998, 'Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor', Journal of Organic Chemistry, vol. 63, no. 23, pp. 8536-8543. https://doi.org/10.1021/jo981170l

TY - JOUR

T1 - Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor

AU - Pierce, Michael E.

AU - Parsons, Rodney L.

AU - Radesca, Lilian A.

AU - Lo, Young S.

AU - Silverman, Stuart

AU - Moore, James R.

AU - Islam, Qamrul

AU - Choudhury, Anusuya

AU - Fortunak, Joseph M.D.

AU - Nguyen, Dieu

AU - Luo, Chi

AU - Morgan, Susan J.

AU - Davis, Wayne P.

AU - Confalone, Pat N.

AU - Chen, Cheng Yi

AU - Tillyer, Richard D.

AU - Frey, Lisa

AU - Tan, Lushi

AU - Xu, Feng

AU - Zhao, Dalian

AU - Thompson, Andrew S.

AU - Corley, Edward G.

AU - Grabowski, Edward J.J.

AU - Reamer, Robert

AU - Reider, Paul J.

PY - 1998/11/13

Y1 - 1998/11/13

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/15644370082

UR - https://www.scopus.com/pages/publications/15644370082#tab=citedBy

U2 - 10.1021/jo981170l

DO - 10.1021/jo981170l

M3 - Article

AN - SCOPUS:15644370082

SN - 0022-3263

VL - 63

SP - 8536

EP - 8543

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 23

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this