Asymmetric Glycine Enolate Aldol Reactions: Synthesis of Cyclosporine's Unusual Amino Acid, MeBmt

Article abstract of DOI:10.1021/ja00281a049

The chiral glycine synthon, 3c, as its derived stannous enolate, has been demonstrated to undergo a highly syn diastereoselective aldol addition reaction with representative aldehydes to give the adducts 5 (R = C6H5, Me, Me2CH) in yields ranging from 71 to 92percent.The utility of these intermediates has been demonstrated via the subsequent three-step transformation of these adducts to the enantiomerically pure N-methyl β-hydroxy amino acids 1.This reaction methodology has been applied to the asymmetric synthesis of (4R)-4-((E)-2-butenyl)-4,N-dimethyl-L-threonine (1a), an important constituent in the immunosuppressant peptide cyclosporine.Several additional structural analogues of 1a were also prepared in conjunction with this study.