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

Sanghee Kim; Eun-Young Kim; Hyojin Ko; Young Hoon Jung

doi:10.1055/s-2003-41073

PAPER

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

Sanghee Kim*^a, Eun-Young Kim^a, Hyojin Ko^a, Young Hoon Jung^b
^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

Abstract

All articles of this category

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

Full Text

References

<A NAME="RF04503SS-1">1</A> Singh SB. Zink DL. Polishook JD. Dombrowski AW. Darkin-Rattray SJ. Schmatz DM. Goetz MA. Tetrahedron Lett. 1996, 37: 8077

<A NAME="RF04503SS-2">2</A> Tani H. Fujii Y. Nakajima H. Phytochemistry 2001, 58: 305

<A NAME="RF04503SS-3">3</A> Darkin-Rattray SJ. Gurnett AM. Myers RM. Dulski PM. Crumley TM. Alloco J. Cannova C. Meinke PT. Colletti SL. Bednarek MA. Singh SB. Goetz MA. Polishook JD. Schmatz DM. Proc. Natl. Acad. Sci. U.S.A. 1996, 93: 13143

<A NAME="RF04503SS-4">4</A> Colletti SL. Li C. Fisher MH. Wyvratt MJ. Meinke PT. Tetrahedron Lett. 2000, 41: 7825 and reference cited therein.

<A NAME="RF04503SS-5">5</A> Rundlett SE. Carmen AA. Kobayashi R. Bavykin S. Turner BM. Grunstein M. Proc. Natl. Acad. Sci. U.S.A. 1996, 93: 14503

<A NAME="RF04503SS-6">6</A> Meinke PT. Colletti SL. Doss G. Myers RW. Gurnett AM. Dulski PM. Darkin-Rattray SJ. Allocco JJ. Galuska S. Schmatz DM. Wyvratt MJ. Fisher MH. J. Med. Chem. 2000, 43: 4919

<A NAME="RF04503SS-7">7</A> Meinke PT. Colletti SL. Ayer MB. Darkin-Rattray SJ. Myers RW. Schmatz DM. Wyvratt MJ. Fisher MH. Tetrahedron Lett. 2000, 41: 7831

<A NAME="RF04503SS-8">8</A> Colletti SL. Myers RW. Darkin-Rattray SJ. Schmatz DM. Fisher MH. Wyvratt MJ. Meinke PT. Tetrahedron Lett. 2000, 41: 7837

<A NAME="RF04503SS-9">9</A> Bajgrowicz JA. El Hallaoui A. Jacquier R. Pigiere C. Viallefont P. Tetrahedron 1985, 41: 1833

<A NAME="RF04503SS-10">10</A> Kuriyama W. Kitahara T. Heterocycles 2001, 55: 1

<A NAME="RF04503SS-11">11</A> Mou L. Singh G. Tetrahedron Lett. 2001, 42: 6603

<A NAME="RF04503SS-12">12</A> Williams RM. Synthesis of Optically Active α-Amino Acids Baldwin JE. Magnus PD. Pergamon; Press Oxford: 1989.

<A NAME="RF04503SS-13A">13a</A> Duthaler RO. Tetrahedron 1994, 50: 1539

<A NAME="RF04503SS-13B">13b</A> Chakraborty TK. Ghosh A. Tetrahedron Lett. 2002, 43: 9691 ; and reference cited therein

<A NAME="RF04503SS-14A">14a</A> Schöllkopf U. Groth U. Deng C. Angew. Chem., Int. Ed. Engl. 1981, 20: 798

<A NAME="RF04503SS-14B">14b</A> Schöllkopf U. Top. Curr. Chem. 1983, 109: 65

<A NAME="RF04503SS-14C">14c</A> Schöllkopf U. Busse U. Lonsky R. Hinrichs R. Liebigs Ann. Chem. 1986, 2150

<A NAME="RF04503SS-15">15</A> Bull SD. Davies SG. Moss WO. Tetrahedron: Asymmetry 1998, 9: 321

Both enantiomers of 8 are commercially available.

<A NAME="RF04503SS-17">17</A> Zang W.-C. Li C.-J. J. Org. Chem. 2000, 65: 5831

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.

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.

<A NAME="RF04503SS-20">20</A> Baldwin JE. Adlington RM. Mitchell MB. Tetrahedron 1995, 51: 5193

<A NAME="RF04503SS-21">21</A> For a previous example employing LDA as a base see: Ohba M. Nishimura Y. Kato M. Fujii T. Tetrahedron 1999, 55: 4999

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]

<A NAME="RF04503SS-23">23</A> Polivin Yu N. Karakhanov RA. Makarashin SV. Russ. Chem. Bull. 1993, 42: 1106

<A NAME="RF04503SS-24">24</A> Flannery RE. Hampton KG. J. Org. Chem. 1972, 37: 280