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Synthesis 2003(14): 2194-2198  
DOI: 10.1055/s-2003-41073
PAPER
© Georg Thieme Verlag Stuttgart · New York

Efficient Syntheses of Biologically Important (S)-2-Amino-8-oxodecanoic Acid (Aoda) and Homologues

Sanghee Kim*a, Eun-Young Kima, Hyojin Koa, Young Hoon Jungb
a Natural Products Research Institute, College of Pharmacy, Seoul National University, 28 Yungun, Jongro, Seoul 110-460, Republic of Korea
Fax: 82(2)7628322; e-Mail: pennkim@snu.ac.kr;
b College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
Further Information

Publication History

Received 20 May 2003
Publication Date:
24 September 2003 (online)

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Abstract

The efficient and practical asymmetric syntheses of the biologically important (S)-2-amino-8-oxodecanoic ester and its homologues have been achieved employing the Schöllkopf chiral auxiliary. Carbon-carbon bond formation between the appropriate alkyl bromide and the LDA generated anion of the Schöllkopf auxiliary, followed by hydrolysis provided the desired methyl ester of a long-chained keto amino acid in high yield with high selectivity.

Key words

alkylation - amino acids - asymmetric synthesis - chiral auxiliaries - diastereoslectivity

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16

Both enantiomers of 8 are commercially available.

18

Analysis by 1H NMR spectroscopy of the crude product indicated that two diastereoisomers of 12 was present in a 1:1 ratio and the desired alkylated bislactim ether 7b was not produced at all.

19

Conversion of each pure diastereoisomers (14b and 15b) to the thermodynamic mixture was studied. In 0.5 M NaOMe-MeOH solution the two diastereoisomers slowly interconvert at r.t. eventually reaching thermodynamic equilibrium within about 1 week to give a 2.9:1 mixture of 14b and 15b.

22

The methyl ester of (S)-Aoda was transformed into the known N-Cbz and C-OMe protected Aoda. The structural assignment of 6b was strongly supported by comparing the spectral data of our synthesized N- and C-protected Aoda with those reported by Singh. [11]