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).
Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors / Bernardi L.; Bonini B.F.; Dessole G.; Fochi M.; Comes-Franchini M.; Gavioli S.; Ricci A.; Varchi G.. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - ELETTRONICO. - 68:4(2003), pp. 1418-1425. [10.1021/jo026616j]
Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors
Bernardi L.;Bonini B. F.;Dessole G.;Fochi M.;Comes-Franchini M.;Ricci A.;Varchi G.
2003
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).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.