Synthesis of mono- and dihydroxy-substituted 2-aminocyclooctanecarboxylic acid enantiomers

(1R,2S,6R)-2-Amino-6-hydroxycyclooctanecarboxylic acid (−)-10 was synthesized from (1R,2S)-2-aminocyclooct-5-enecarboxylic acid (+)-2 via an iodolactone intermediate, while (1R,2S,3R,4S)-2-amino-5,6-dihydroxycyclooctanecarboxylic acid (−)-12 was prepared by using the OsO4-catalyzed oxidation of Boc-protected amino ester (−)-5. The stereochemistry and relative configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy (based on 2D NOE cross-peaks and 3J(H,H) coupling constants) and X-ray crystallography.

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(1R,2S)-2-tert-Butoxycarbonylaminocyclooct-5-enecarboxylic acidC14H23NO4Ee = >99%[α]D20=-59 (c 1, EtOH)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S)

Ethyl (1R,2S)-2-tert-butoxycarbonylaminocyclooct-5-enecarboxylateC16H27NO4Ee = >99%[α]D20=-53.4 (c 1, EtOH)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S)

(1R,2S,5S,6S)-2-(tert-Butoxycarbonylamino)-5-iodo-7-oxabicyclo[4.2.2]decan-8-oneC14H22INO4Ee = >99%[α]D20=-76.2 (c 1, EtOH)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,5S,6S)

(1R,2S,6R)-2-(tert-Butoxycarbonylamino)-7-oxabicyclo[4.2.2]decan-8-oneC14H23NO4Ee = >99%[α]D20=-93.1 (c 0.5, EtOH)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,6R)

(1R,2S,6R)-2-Amino-7-oxabicyclo[4.2.2]decan-8-one hydrochlorideC9H16ClNO2Ee = >99%[α]D20=-23.9 (c 0.4, H2O)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,6S)

(1R,2S,6R)-2-Amino-6-hydroxycyclooctanecarboxylic acidC9H17NO3Ee = >99%[α]D20=-9 (c 0.4, H2O)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,6R)

Ethyl (1R,2S,5R,6S)-2-tert-butoxycarbonylamino-5,6-dihydroxycyclooctanecarboxylateC16H29NO6Ee = >99%[α]D20=-27.2 (c 1, EtOH)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,5R,6S)

(1R,2S,5R,6S)-2-Amino-5,6-dihydroxycyclooctanecarboxylic acidC9H17NO4Ee = >99%[α]D20=-7.6 (c 0.48, H2O)Source of chirality: enzymatic resolution of (±)-9-azabicyclo[6.2.0]dec-4-en-10-oneAbsolute configuration: (1R,2S,5R,6S)