Synthesis of (−)-dihydropinidine, (2S,6R)-isosolenopsin and (+)-monomorine via a chiral synthon from l-aspartic acid

The use of a β-amino aldehyde derived from l-aspartic acid as a chiral synthon to construct 2,6-disubstituted piperidines is described. The synthesis of (−)-dihydropinidine·HCl, (2S,6R)-isosolenopsin·HCl and (+)-monomorine has been achieved from this chiral synthon using a Wittig reaction followed by hydrogenation (reductive cyclization) as the key steps.

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(S)-Benzyl 1-(tert-butyldimethylsilyloxy)-4-oxobutan-2-ylcarbamateC18H29NO4Si[α]D27=-10.3 (c 1.05, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (S)

(S,E)-Benzyl 1-(tert-butyldimethylsilyloxy)-6-oxohept-4-en-2-ylcarbamateC21H33NO4Si[α]D26=-10.7 (c 1.34, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (S)

(2S,6S)-2-((tert-Butyldimethylsilyloxy)methyl)-6-methyl-piperidineC13H29NOSi[α]D20=-7.4 (c 1.0, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)

(2S,6S)-1-Benzyl-2-((tert-butyldimethylsilyloxy)methyl)-6-methylpiperidineC20H35NOSi[α]D23=-13.9 (c 1.0, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)

((2S,6S)-1-Benzyl-6-methylpiperidin-2-yl)methanolC14H21NO[α]D20=+22.8 (c 0.8, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)

(2S,6S)-1-Benzyl-2-methyl-6-((E)-prop-1-enyl)piperidineC16H23N[α]D29=-17.2 (c 0.9, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)

(2S,6S)-1-Benzyl-2-methyl-6-((E)-non-1-enyl)piperidineC22H35N[α]D27=-15.5 (c 1.1, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)

(E)-1-((2S,6S)-1-Benzyl-6-methylpiperidin-2-yl)hept-1-en-3-oneC20H29NO[α]D29=+11.1 (c 0.7, CHCl3)Source of chirality: l-Aspartic acidAbsolute configuration: (2S,6S)