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Synthesis 2008(23): 3810-3818  
DOI: 10.1055/s-0028-1083634
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Neoechinulin A and Derivatives

Kouji Kuramochia,1, Toshiaki Aokia,b,1, Atsuo Nakazakib, Shinji Kamisukia,c, Masahiro Takenoc, Kensuke Ohnishia,b, Kuniaki Kimotoc, Nobuo Watanabec, Takashi Kamakurac, Takao Araic, Fumio Sugawaraa,c, Susumu Kobayashi*a,b
a Genome and Drug Discovery Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Fax: +1(81)471213671 ; e-Mail: kobayash@rs.noda.tus.ac.jp;
b Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
c Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Further Information

Publication History

Received 4 July 2008
Publication Date:
06 November 2008 (online)

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Abstract

Neoechinulin A isolated from Eurotium rubrum showed cytoprotection activity against peroxynitrite generated from SIN-1 [3-(4-morpholinyl)sydnonimine hydrochloride] in PC12 cells. As we are interested in this biological activity, we synthesized neoechinulin A and its derivatives. In this article, we fully report the isolation of natural neoechinulin A and B, a total synthesis of (-)-neoechinulin A, and determination of the absolute configuration of natural neoechinulin A. In addition, we describe herein syntheses of neoechinulin A derivatives, including a biotinylated neoechinulin A derivative, which will be useful for identification of the binding proteins of neoechinulin A.

Key words

alkaloids - natural products - indoles - amino acids - antibiotics

1

These authors contributed equally to this work.

34

Since compound 15 was insoluble in chromatographic solvents, we could not determine the enantiomeric excess of our synthetic 15. The specific rotation of 15 was [α]D ²5 -15.2 (c 0.43, DMF) {Lit. [³³] [α]D ²0 -10 (c 1.0, DMF)}. Since no significant difference in the activity was observed between (-)-1 and (+)-1, we prepared compound 15 in a straight-forward manner by condensation of 19 with 4b.