TY - JOUR
T1 - Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors
AU - Bernardi, Luca
AU - Bonini, Bianca F.
AU - Dessole, Gabriella
AU - Fochi, Mariafrancesca
AU - Comes-Franchini, Mauro
AU - Gavioli, Silvia
AU - Ricci, Alfredo
AU - Varchi, Greta
PY - 2003/2/21
Y1 - 2003/2/21
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=0037458973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037458973&partnerID=8YFLogxK
U2 - 10.1021/jo026616j
DO - 10.1021/jo026616j
M3 - Article
C2 - 12585882
AN - SCOPUS:0037458973
VL - 68
SP - 1418
EP - 1425
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 4
ER -