A new asymmetric synthesis of (2S,3R,4R,5S)-trihydroxypipecolic acid

A novel four step synthesis of enantiomerically pure (2S,3R,4R,5S)-trihydroxypipecolic acid, starting from readily available materials, that is, condensation products of (R)-(−)-phenylglycinol with a mesotrihydroxylated glutaraldehyde, is described. The scope and limitations of the reaction have also been investigated.

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Hexahydro-3-phenyl-6,7,8-tribenzyloxy-(3R)-[3α,5β,6α,7β,8α,8aβ]-5H-oxazolo[3,2-a]pyridine-5-carbonitrileC35H34N2O4[α]D = −35 (c 0.2, CHCl3)Source of chirality: (R)-(−)-phenylglycinol and isopropylidene-α-d-glucofuranose

3,4,5-Tribenzyloxy-1-(2-hydroxy-1-phenyl-ethyl)-(1R)-[1α,2β,3β,4α,5β]piperidine-2-carbonitrileC35H36N2O4[α]D = −36 (c 0.4, CHCl3)Source of chirality: (R)-(−)-phenylglycinol and isopropylidene-α-d-glucofuranose

Hexahydro-4-phenyl-7,8,9-tribenzyloxy-(4S)-[1aβ,4 β,9α,8β,7α]-pyrido[2,1-c][1,4]oxazin-1-oneC35H35NO5[α]D = −29 (c 0.02, CHCl3).Source of chirality: (R)-(−)-phenylglycinol and isopropylidene-α-d-glucofuranose

(2S,3R,4R,5S)-Trihydroxy-pipecolic acidC6H11NO5[α]D = +18 (c 0.01, H2O)Source of chirality: (R)-(−)-phenylglycinol and isopropylidene-α-d-glucofuranose

3,4,5-Tribenzyloxy-1-(2-hydroxy-1-phenyl-ethyl)-(1R)-[1α,2β,3α,4β,5α]piperidine-2-carbonitrileC35H36N2O4[α]D = −5 (c 0.2, CHCl3)Source of chirality: (R)-(−)-phenylglycinol and isopropylidene-α-d-glucofuranose