Asymmetric syntheses of (−)-epi-pseudoconhydrine and (−)-5-hydroxysedamine based on a cis-diastereoselective 1,4-asymmetric induction

The asymmetric syntheses of (−)-epi-pseudoconhydrine and (−)-5-hydroxysedamine are reported. The key to these syntheses is an unusual highly cis-diastereoselective 1,4-asymmetric induction in the α-amidoallylation of the new chiral building block 15.

Figure optionsDownload as PowerPoint slide

(S)-N-(4-Methoxybenzyl)-2,5-dihydroxypentanamideC13H19NO4[α]D20=-23.8 (c 1.0, CH3OH)Source of chirality: (S)-glutamic acidAbsolute configuration: (S)

(3S,6S)-1-(4-Methoxybenzyl)-6-allyl-2-oxopiperidin-3-yl acetateC18H23NO4[α]D20=+44.0 (c 1.0, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(3S,6S)-1-(4-Methoxybenzyl)-6-allylpiperidin-3-olC16H23NO2[α]D20=-73.9 (c 1.1, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(−)-(2R,5S)-epi-Pseudoconhydrine hydrochloride saltC8H17NO·HCl[α]D20=-10.2 (c 1.0, EtOH)Source of chirality: (S)-glutamic acidAbsolute configuration: (2R,5S)

(3S,6S)-1-(4-Methoxybenzyl)-6-(2-oxo-2-phenylethyl)-3-(tetrahydro-2H-pyran-2-yloxy)piperidin-2-oneC26H31NO5[α]D20=-65.4 (c 1.0, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(3S,6S)-1-(4-Methoxybenzyl)-3-hydroxy-6-(2-oxo-2-phenylethyl)piperidin-2-oneC21H23NO4[α]D20=-10.6 (c 1.1, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(3S,6S)-1-(4-Methoxybenzyl)-6-((S)-2- hydroxy-2-phenylethyl)piperidin-3-olC21H27NO3[α]D20=-59.3 (c 1.0, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(2S,5S)-tert-Butyl 5-hydroxy-2-((S)-2-hydroxy-2-phenylethyl)piperidine-1-carboxylateC18H27NO4[α]D20=-62.4 (c 0.8, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (2S,5S,2′S)

(3S,6S)-6-((S)-2-Hydroxy-2-phenylethyl)-1-methylpiperidin-3-olC14H21NO2[α]D20=-53.4 (c 0.5, MeOH)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S,2′S)

(3S,6S)-1-(4-Methoxybenzyl)-2-oxo-6-(2-oxoethyl)piperidin-3-yl acetateC17H21NO5[α]D20=+51.0 (c 1.0, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)

(3S,6S)-1-(4-Methoxybenzyl)-6-(2-oxo-2-phenylethyl)-2-oxopiperidin-3-yl acetateC23H25NO5[α]D20=+6.9 (c 1.4, CHCl3)Source of chirality: (S)-glutamic acidAbsolute configuration: (3S,6S)