Synthesis, Based On The Diversity Of Chiral Vicinal Amino Alcohols

Optically activeβ-amino alcohols are versatile building blocks for medicinal chemistry and natural product synthesis.A general method for the construction of homochiral syn-1,2-amino alcohol and syn-1,2-diamine was established from anti-1,2-amino alcohol obtained by SmI₂-induced reductive coupling of N-tert-butanesulfinyl imines with aldehydes.This strategy was successfully applied to the syntheses of (+)-CP-99,994,(+)-L-733,060,(2S,3R)-and(2S,3S)-3-hydroxy pipecolic acids, (2R,3R)-and(2R,3S)-3-hydroxy-2-hydroxymethyl piperidines as well as a series of unnaturalα- amino acids beating chiral 2-heterocyclic substitutions.1,Mesylation of the key intermediate derived from SmI₂-induced reductive coupling of N-tert-butanesulfinyl imine with aldehyde followed by azide displacement provided syn-1,2-diamine.(+)-CP-99,994 can be synthesized in 6 steps under 3 operations.Intramolecular S_N2 reaction established the required chiral centers through an oxazoline,and(+)-L-733,060 can be obtained in 7 steps from the key intermediate.2,With a similar strategy,both cis- and trans-3-hydroxy-L-pipecolic acids are synthesized from a common chiral intermediate via a short and flexible route.(2S,3 S)-3-Hydroxypipecolic Acid and analog was obtained in 9 and 8 linear steps from a key anti-1,2-amino alcohol intermediate.Stereospecific inversion of 3-OH is achieved by the formation of an oxazoline followed by acidic ring cleavage. (2S,3R)-3-hydroxypipecolic acid and analog can be successfully obtained in 9 and 8 linear steps from the syn-1,2-amino alcohol through the similar process.3,A novel method which can provide a facile access to several unnatural amino acids with chiral 2-heterocyclic substitutions is developed,using analogous 1,2-amino alcohol intermediates.