Stereoselective synthesis of 3-deoxy-piperidine iminosugars from l-lysine

A new method using electrochemical oxidation and/or OsO4 oxidation has been used for the stereoselective synthesis of 2,3,6-trihydroxylated (5S)-piperidine derivatives. The electrochemical method was successively used for the conversion of N-protected piperidines to N-protected 1-methoxypiperidines and for the conversion of 2,3-didehydro-1-methoxypiperidine derivatives to 2,3-trans-1,2,3-triacetoxypiperidine derivatives. These triacetates were easily transformed into (2S,3S)-6-triacetoxy-(5S)-methylpiperidine and (2R,3R)-6-triacetoxy-(5S)-methylpiperidine. In addition, the 2,3-cis-dihydroxylation of 2,3-didehydro-1-methoxypiperidine derivatives with OsO4 afforded (2R,3S)-6-triacetoxy-(5S)-methylpiperidine and (2S,3R)-6-triacetoxy-(5S)-methylpiperidine.

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(5S)-Acetoxymethyl-N-methoxycarbonylpiperidineC10H17NO4[α]D28=-45.6 (c 1.1, CHCl3)Source of chirality: l-pipecolinic acidAbsolute configuration: (5S)

(5S)-Acetoxymethyl-1,2-didehydro-N-methoxycarbonylpiperidineC10H15NO4[α]D27=-72.2 (c 1.2, methanol)Source of chirality: l-lysineAbsolute configuration: (5S)

(2S)-6-Bis(methoxycarbonylamino)hexyl acetateC12H22N2O6[α]D28=+17.1 (c 1.0, methanol)Source of chirality: l-lysineAbsolute configuration: (2S)

(2S,3S)-Diacetoxy-(5S)-acetoxymethyl-N-methoxycarbonylpiperidineC14H21NO8[α]D26=+40.0 (c 0.5, CHCl3)Source of chirality: l-lysineAbsolute configuration: (2S,3S,5S)

(5S)-N-Bis(methoxycarbonyl)piperidineC9H15NO4[α]D25=-60.9 (c 1.5, methanol)Source of chirality: l-pipecolinic acidAbsolute configuration: (5S)

1,2-Didehydro-(5S)-N-bis(methoxycarbonyl)piperidineC9H13NO4[α]D27=-46.9 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (5S)

(6S)-1-Aza-2,3-didehydro-8-oxabicyclo[4.3.0]nonan-9-oneC7H9NO2[α]D28=+164.9 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (6S)

Methyl (2S)-6-bis(methoxycarbonylamino)hexanoateC11H20N2O6[α]D28=+16.5 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (2S)

(3R,4R,6S)-3,4-Diacetoxy-1-aza-8-oxabicyclo[4.3.0]nonan-9-oneC11H15NO6[α]D26=-75.2 (c 0.6, CHCl3)Source of chirality: l-lysineAbsolute configuration: (3R,4R,6S)

(2S,3R)-Diacetoxy-(5S)-acetoxymethyl-N-methoxycarbonylpiperidineC14H21NO8[α]D30=+37.0 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (2S,3R,5S)

(5S)-Acetoxymethyl-(2S,3R)-dihydroxy-N-methoxycarbonylpiperidineC10H17NO6[α]D30=-6.0 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (2S,3R,5S)

(5S)-Acetoxymethyl-(2S,3R)-bis(p-toluenesulfonyloxy)-N-methoxycarbonylpiperidineC24H29NO10S2[α]D30=+32.4 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (2S,3R,5S)

(3R,4S,6S)-3,4-Diacetoxy-1-aza-8-oxabicyclo[4.3.0]nonan-9-oneC11H15NO6[α]D29=-48.0 (c 0.5, CHCl3)Source of chirality: l-lysineAbsolute configuration: (3R,4S,6S)

(6S)-1-Aza-3,4-didehydro-8-oxabicyclo[4.3.0]nonan-9-oneC7H9NO2[α]D30=-166.9 (c 1.0, CHCl3)Source of chirality: l-lysineAbsolute configuration: (6S)