Stereoselective Synthesis of (+)-Polyoxamic Acid Starting with a Chiral ­Aziridine

Abstract

An efficient and stereoselective synthesis of (+)-polyoxamic acid was developed. The route starts with the commercially available 1-(R)-α-methylbenzylaziridine-2-methanol, a substance that has not been used previously as a starting material for the preparation of this target. The route also features the use of a stereocontrolled Sharpless asymmetric dihydroxylation reaction, promoted by AD-mix-α, which is followed by a regioselective aziridine ringopening process, to generate the basic skeleton of target natural product. Subsequent oxidation and global deprotection produces (+)-polyoxamic acid.

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

“…PF-00951966 (Scheme 18) belongs to a fluoroquinolone family of antibiotics which is substituted at C7 with a (3 R )-3-[(1 S )-2-cyano-1-(methylamino)ethyl]pyrrolidin-1-yl group [64]. The synthesis of the corresponding pyrrolidine (3 S ,3' R )- 68 began from the aziridine ( E )-acrylate (2 R ,1' S )- 69a (Scheme 18) readily prepared from the aldehyde (2 S ,1' S )- 6 [31]. Michael addition of nitromethane to the acrylate (2 R ,1' S )- 69a gave an inseparable mixture (70:30) of aziridine esters 70 which were subjected to a selective reduction of the nitro group to afford the major pyrrolidine-2-one (2 R ,4' R ,1'' S )- 71 after chromatographic purification [65].…”

“…Syntheses of 1,4-dideoxy-1,4-imino-ᴅ-arabinitol ((2 R ,3 R ,4 R )- 182 ) and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ((2 R ,3 S ,4 S )- 182 ) were accomplished starting from the aziridine ( E )-acrylate (2 S ,1' R )- 69b readily prepared from the aldehyde (2 R ,1' R )- 6 (Scheme 48) [31]. The ( E )-acrylate was subjected to cis -dihydroxylation to give a 1:1 mixture of the diastereoisomeric diols 145a and 145b [103].…”