Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors.
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).
Bernardi
Luca
L
Dipartimento di Chimica Organica A. Mangini, Facoltà di Chimica Industriale, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy.
Bonini
Bianca F
BF
Dessole
Gabriella
G
Fochi
Mariafrancesca
M
Comes-Franchini
Mauro
M
Gavioli
Silvia
S
Ricci
Alfredo
A
Varchi
Greta
G
D000605:Amino Alcohols / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000605:Amino Alcohols; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D008094:Lithium