Asymmetric Synthesis of β-Amino-α-Hydroxy Acids through Lewis Acid-Mediated Addition of Ketene Acetal to Imines

Abstract

Asymmetric synthesis of β-amino-α-hydroxy acids, key components of medicinally important molecules including Paclitaxel, KRI-1314, amastatin, and microginin, has been attained from the aldimine coupling of chiral imines N-alkylidene-(S)- or (R)-α-methylbenzylamine with (Z)-α-methoxyketene methyltrimethylsilyl acetal, followed by demethylation, hydrogenolysis, and hydrolysis.

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

“…This fact led to several approaches for the stereoselective synthesis of (2 S ,3 R )-AHDA including (i) the enantioselective introduction of amino- and hydroxy-groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10–15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed multicomponent condensation reactions of aldehyde, an amine and ketene silyl acetal derivatives to get the vicinal hydroxylamino acids [17]. In addition, a few strategies employ a chiral pool approach.…”