Efficient synthesis of 3,4- and 4,5-dihydroxy-2-amino-cyclohexanecarboxylic acid enantiomers

An efficient method for the synthesis of (1S,2R,4R,5S)- and (1R,2R,4R,5S)-2-amino-4,5-dihydroxycyclohexanecarboxylic acids (−)-6 and (−)-9 and (1R,2R,3S,4R)- and (1S,2R,3S,4R)-2-amino-3,4-dihydroxycyclohexanecarboxylic acids (−)-15 and (−)-18 was developed by using the OsO4-catalyzed oxidation of Boc-protected (1S,2R)-2-aminocyclohex-4-enecarboxylic acid (+)-2 and (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (+)-11. Good yields were obtained. The stereochemistry of the synthesized compounds was proven by NMR spectroscopy.

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Ethyl (1S,2R,4R,5S)-2-tert-butoxycarbonylamino-4,5-dihydroxycyclohexanecarboxylateC14H25NO6Ee = >99%[α]D20=+27.3 (c 0.49, EtOH)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1S,2R,4R,5S)

(1S,2R,4R,5S)-2-Amino-4,5-dihydroxycyclohexanecarboxylic acidC7H13NO4Ee = >99%[α]D20=-11.7 (c 0.35, H2O)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1S,2R,4R,5S)

(1S,2R,4R,5S)-2-Amino-4,5-dihydroxycyclohexanecarboxylic acid hydrochlorideC7H14ClNO4Ee = >99%[α]D20=+7.3 (c 0.324, H2O)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1S,2R,4R,5S)

Ethyl (1R,2R)-2-tert-butoxycarbonylaminocyclohex-4-enecarboxylateC14H23NO4Ee = >99%[α]D20=-23.7 (c 0.5, EtOH)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1R,2R)

Ethyl (1R,2R,4R,5S)-2-tert-butoxycarbonylamino-4,5-dihydroxycyclohexanecarboxylateC14H25NO6Ee = >99%[α]D20=-25.2 (c 0.51, EtOH)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1R,2R,4R,5S)

(1R,2R,4R,5S)-2-Amino-4,5-dihydroxycyclohexanecarboxylic acidC7H13NO4Ee = >99%[α]D20=-56 (c 0.37, H2O)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1R,2R,4R,5S)

(1R,2R,4R,5S)-2-Amino-4,5-dihydroxycyclohexanecarboxylic acid hydrochlorideC7H14ClNO4Ee = >99%[α]D20=-48.8 (c 0.46, H2O)Source of chirality: enzymatic resolution of ethyl cis-2-aminocyclohex-4-enecarboxylateAbsolute configuration: (1R,2R,4R,5S)

Ethyl (1R,2S)-2-tert-butoxycarbonylaminocyclohex-3-enecarboxylateC14H23NO4Ee = >99%[α]D20=+165.2 (c 0.55, EtOH)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1R,2S)

Ethyl (1R,2R,3S,4R)-2-tert-butoxycarbonylamino-3,4-dihydroxycyclohexanecarboxylateC14H25NO6Ee = >99%[α]D20=-43.2 (c 0.54, EtOH)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1R,2R,3S,4R)

(1R,2R,3S,4R)-2-Amino-3,4-dihydroxycyclohexanecarboxylic acidC7H13NO4Ee = >99%[α]D20=-81.4 (c 0.35, H2O)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1R,2R,3S,4R)

(1R,2R,3S,4R)-2-Amino-3,4-dihydroxycyclohexanecarboxylic acid hydrochlorideC7H14ClNO4Ee = >99%[α]D20=-84.8 (c 0.55, H2O)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1R,2R,3S,4R)

Ethyl (1S,2S)-2-tert-butoxycarbonylaminocyclohex-3-enecarboxylateC14H23NO4Ee = >99%[α]D20=+103.6 (c 0.53, EtOH)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1S,2S)

Ethyl (1S,2R,3S,4R)-2-tert-butoxycarbonylamino-3,4-dihydroxycyclohexanecarboxylateC14H25NO6Ee = >99%[α]D20=-12 (c 0.28, EtOH)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1S,2R,3S,4R)

(1S,2R,3S,4R)-2-Amino-3,4-dihydroxycyclohexanecarboxylic acidC7H13NO4Ee = >99%[α]D20=-5.2 (c 0.38, H2O)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1S,2R,3S,4R)

(1S,2R,3S,4R)-2-Amino-3,4-dihydroxycyclohexanecarboxylic acid hydrochlorideC7H14ClNO4Ee = >99%[α]D20=-61.5 (c 0.5, H2O)Source of chirality: enzymatic resolution of (±)-7-azabicyclo[4.2.0]oct-4-en-8-oneAbsolute configuration: (1S,2R,3S,4R)