Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors |
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Authors: | Bernardi Luca Bonini Bianca F Dessole Gabriella Fochi Mariafrancesca Comes-Franchini Mauro Gavioli Silvia Ricci Alfredo Varchi Greta |
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Affiliation: | Dipartimento di Chimica Organica A. Mangini, Facoltà di Chimica Industriale, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy. |
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Abstract: | A new protocol is described for the stereocontrolled synthesis of pseudo-C(2)-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-C(2)-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). |
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