129822-17-9Relevant academic research and scientific papers
Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors
Bernardi, Luca,Bonini, Bianca F.,Dessole, Gabriella,Fochi, Mariafrancesca,Comes-Franchini, Mauro,Gavioli, Silvia,Ricci, Alfredo,Varchi, Greta
, p. 1418 - 1425 (2007/10/03)
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).
Grignard addition to aldonitrones. Stereochemical aspects and application to the synthesis of C2-symmetric diamino alcohols and diamino diols
Dondoni, Alessandro,Perrone, Daniela,Rinaldi, Marilisa
, p. 9252 - 9264 (2007/10/03)
A new example of the stereoselective installation of the amino group at a saturated carbon center via organometallic addition of chiral aldehydes to nitrones is illustrated by the synthesis of 1,3-diamino propanol 1 and 1,4- diamino butandiol 2 units. Three diamino alcohol 1 stereotriads were obtained by stereoselective addition of alkylmagnesium halides (benzyl, cyclohexylmethyl, and metallyl) to the N-benzyl nitrones derived from β- amino-α-hydroxy aldehydes followed by reduction of the resulting N- benzylhydroxylamines. Three 1,4-dibenzyl substituted stereoisomers of type 2 with fixed S configuration at C2 and C3 were prepared by sequential and simultaneous amination in two directions starting from L-threose nitrone and L-tartraldehyde bis-nitrone, respectively. The R,S,S,R isomer obtained by the former route was converted into a seven-membered ring cyclic urea (1,3- diazapin-2-one), i.e., a compound that belongs to a class of nonpeptide HIV- 1 protease inhibitors.
Stereocontrolled synthesis of pseudo C2-symmetric 1,3-diamino-2-propanol core units of HIV protease inhibitors
Dondoni, Alessandro,Perrone, Daniela
, p. 499 - 502 (2007/10/03)
The synthesis of the pseudo C2-symmetric dibenzyldiamino alcohol (S,S)-1 and the two meso stereoisomers 1a and 1b (R = PhCH2) is described by stereocontrolled benzylmagnesium chloride addition to the nitrones 3 derived from chiral β-amino-α-hydroxy aldehydes 2 that in turn were obtained from phenylalanino; the overall yield of (S,S)-1 is 23% from N-Boc L-phenylalaninal; the antipode (R,R)-1 can be prepared in a similar way starting from the D-isomer of the same α-amino aldehyde.
Stereocontrolled Synthesis of C2-Symmetric and Pseudo-C2-Symmetric Diamino Alcohols and Diols for Use in HIV Protease Inhibitors
Kempf, Dale J.,Sowin, Thomas J.,Doherty, Elizabeth M.,Hannick, Steven M.,Codavoci, LynnMarie,et al.
, p. 5692 - 5700 (2007/10/02)
The stereocontrolled syntheses of dibenzyldiamino alcohol 1 and dibenzyldiamino diols 2-4, core units of potent C2-symmetric and pseudo-C2-symmetric inhibitors of HIV protease, are described, starting from phenylalanine.Stereoselecti
