Studies Concerned with the Structure and Synthesis of the Anti‐viral Tropolone Glycoside Liriosmaside A

The core of the anti-viral troponoid natural product liriosmaside A lacking the 3-hydroxy-3-methylglutaric acid (HMGA) side-chain at C6′ has been prepared. The early steps involved the gem-dibromocyclopropane-mediated ring-expansion of a readily-obtained Robinson annulation product. These were followed by the Pd[0]-catalysed glucosylation of the resulting racemic bromotropone and the structure of the chromatographically separated R-isomer was established by single-crystal X-ray analysis.

Abstract

A bromotropone corresponding to the agylcone of the glycosylated sesquiterpenoid natural product liriosmaside A has been prepared over ten steps and in a fully regio-controlled manner through the gem-dibromocyclopropane-mediated ring-expansion of a readily accessible decalenone. A Pd[0]-mediated glucosylation reaction applied to this bromotropone afforded a product mixture from which an enantiomerically pure cross-coupling product could be obtained and its structure confirmed through single-crystal X-ray analysis of a derivative. Various (unsuccessful) attempts are described to selectively acylate the last compound and thereby install the 3-hydroxy-3-methylglutaric acid or HMGA-containing side chain of the title natural product. A literature survey of other natural products embodying the HMGA motif suggest that liriosmaside A and its co-metabolite liriosmaside B could be S-configured at C3”. The evaluation of the glucosylated tropone in a series of anti-bacterial, anti-fungal and cytotoxicity assays reveals that it is inactive in all of these and so emphasizing the prospect that this and related troponoids, including the natural products liriosmaside A and B, can serve as useful models for new anti-viral agents.

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