A new approach for the asymmetric synthesis of (2S,3S)-3-hydroxypipecolic acid

An efficient stereoselective synthesis of (2S,3S)-3-hydroxypipecolic acid was achieved from (S)-glutamic acid via the furylation of an N-protected 6-hydroxy-2-piperidinone using furan as a nucleophile and the oxidation of the furyl group to a carboxylic group as the key steps.

Figure optionsDownload as PowerPoint slide

(5S,6R)-1-Benzyl-5-benzyloxy-6-hydroxy-2-piperidinoneC19H21NO3[α]D25=-29.8(c1.0,CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (5S,6R)

(5S,6S)-1-Benzyl-5-benzyloxy-6-(2-furyl)-2-piperidinoneC23H23NO3[α]D25=-54.9(c0.8,CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (5S,6S)

(5S,6S)-1-Benzyl-5-benzyloxy-2-piperidinone-6-carboxylic acidC20H21NO4[α]D25=-109.9(c1.0,CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (5S,6S)

(5S,6S)-1-Benzyl-5-benzyloxy-2-piperidinone-6-carboxylic acid methyl esterC21H23NO4[α]D20=-52.9(c2.1,CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (5S,6S)

(2S,3S)-1-Benzyl-3-benzyloxypiperidine-2-carboxylic acid methyl esterC21H25NO3[α]D25=-19.0(c1.5,CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (2S,3S)

(2S,3S)-3-Hydroxypipecolic acidC6H11NO3[α]D25=+13.3(c0.7,10%aq HCl)Source of chirality: (S)-glutamic acidAbsolute configuration: (2S,3S)