Synthesis 2006(5): 831-838  
DOI: 10.1055/s-2006-926326
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Facile Synthesis and Enzymatic Resolution of Naturally Occurring Remotely­ Functionalized Alkylmethylmaleic Anhydrides from Aspergillus wentii: Aspergillus Acids A-D [1]

Srinivasan Easwar, Narshinha P. Argade*
Combi Chem-Bio Resource Centre, Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Fax: +91(20)25893153; e-Mail: np.argade@ncl.res.in;
Further Information

Publication History

Received 20 July 2005
Publication Date:
07 February 2006 (online)

Abstract

The first synthesis of four new naturally occurring remotely functionalized secondary mould metabolite anhydrides 1a-d is described starting from N-p-tolyl citraconimide (5) in three to six steps and 20-65% overall yields. The condensation of triphen­ylphosphine-maleimide adduct 6 with aldehyde 4 furnished the exo-imide 7, which after isomerization, hydrolysis, and acylation gave aspergillus acid A (1a) in 54% overall yield in four steps. The condensation of adduct 6 with aldehyde 15 similarly afforded the desired imide 17 in two steps. The acid-catalyzed hydrolysis of imide 17 directly furnished aspergillus acid B (1b), exposing the latent methyl ketone present as the terminal acetylene. Sodium borohydride induced chemoselective reduction of aspergillus acid B (1b) gave aspergillus acid C (1c), which upon acetic anhydride induced acylation, furnished aspergillus acid D (1d). A facile Amano PS catalyzed acylation of aspergillus acid C (1c) gave, in good yield, the desired (+)-aspergillus acid C (1e) in 70% ee and (-)-aspergillus acid D (1f) in 72% ee. In the present enzymatic reaction, the anhydride moiety presumably plays a crucial role in the substrate recognition, binding, and resolution process.

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NCL Communication No. 6686.

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NCL Communication No. 6686.