Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors

Luca Bernardi, Bianca F. Bonini, Gabriella Dessole, Mariafrancesca Fochi, Mauro Comes-Franchini, Silvia Gavioli, Alfredo Ricci, Greta Varchi

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

A new protocol is described for the stereocontrolled synthesis of pseudo-C2-symmetric core units of interest as candidates for HIV protease inhibition. Addition of unbranched and branched organolithium reagents to cyanohydrins from L-phenylalaninal and L-isoleucinal, followed by in situ reduction of the intermediate imines and CHT deprotection under MW irradiation, led to 1,3-diamino alcohols 6a and 8a as the major products in satisfactory to good yields. The first preparation of a previously unreported pseudo-C2-symmetric triamino derivative was accomplished expeditiously via high-yielding nitro-Mannich addition of the silylnitronate, from 2-phenyl-1-nitroethane, to the PMP imine derived from L-phenylalaninal. Reduction of the nitro group in the moderately unstable nitro diamine adduct, followed by chromatographic separation of the required diastereoisomer and CHT debenzylation under MW irradiation, led to the 2-PMP-protected triamine 19 isolated as a bis(sulfonamide).

Original languageEnglish (US)
Pages (from-to)1418-1425
Number of pages8
JournalJournal of Organic Chemistry
Volume68
Issue number4
DOIs
StatePublished - Feb 21 2003

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Concise and stereocontrolled synthesis of pseudo-C<sub>2</sub>-symmetric diamino alcohols and triamines for use in HIV protease inhibitors'. Together they form a unique fingerprint.

Cite this