Spiculisporic acid

MacMillan reported a short and effective synthesis of spiculisporic acid which elegantly exemplified his Mukaiyama-Michael addition of silyloxyfurans to a,P-unsatu-rated aldehydes [88], Robichaud and Tremblay augmented this in a formal synthesis of compactin [224], Within this report it was shown that low enantioselectivities were obtained in the conjugate addition to aCTolein. Use of p-silyl acrolein 177 circumvented this and gave butenohde 178 in 95% yield and 82% ee. Conversion of adduct 178 to the decaUn (179) in eight steps resulted in a formal synthesis (Scheme 71). 

While Lewis acids normally enable l,2-additi(Mis of silyloxy furans to a,(3-unsaturated aldehydes, the MacMillan group discovered that iminium catalysis favors 1,4-additions, thus overcoming the deficiency of normal Lewis acids in Mukaiyama-Michael additions 244). The high potential of this protocol was demonstrated impressively in a short synthesis of the Penicillium spiculisporum fermentation product spiculisporic acid (262). As shown in Scheme 60, vinylogous addition of the silyloxy furan 263 to the acceptor 264 catalyzed by 228 furnished the key intermediate 265 in good enantio- and diastereoselectivity. It is worth noting that the TfOH salt of the catalyst in combination with methyl ester 266 as a Michael acceptor gave the anh-diastereomer 267 exclusively. This compound was then used for the synthesis of 5-epi-spiculisporic acid (268) (Scheme 60) 244). 

Scheme 60 Iminium-catalyzed Mukaiyama-Michael addition in the synthesis of spiculisporic acid (262)...

Spiculisporic acid has been known as a trace component of lichenous bodies since 1941. Tabuchi s group developed a new bioindustrial process for the efficient production of this tricarboxylic-type surfactant (Fig. 8) from glucose as carbon source with yields up to 110 g/L (Table 3) using the fungus Penicillium spiculisporian [70,71]. The native product has been chemically... 

Spiculisporic acid (4,5-dicarboxy-4-pentadecanolide) is supplied from Iwata Chemical Co. Ltd. (Shizuoka, Japan). 

Recently, four microbially derived biosurfactants—rhamnolipids, sophoro-lipids, spiculisporic acid and surfactin—are commercially available. Nevertheless, the use of biosurfactants is limited by the cost of production and insufficient experience in applications. However, since there is increasing awareness of water quality and environmental conservation, as well as expanding demand for natural products in cosmetics or in pharmaceutical products, it appears inevitable that high-quality microbially produced biosurfactants will replace the currently used chemical products in many applications outlined above. In addition, in the future chemically or bio-... 

Gatenbeck, S., and Mahlen, A. (1966). The enzymic synthesis of spiculisporic acid. In Antibiotics, Proceedings of the Congress on Antibiotics, Prague 1964, p. 540. Butterworth, London. 

Preformed enolates such as silyl enol ethers can he used as donors in the addition of a, 8-unsaturated aldehydes (Mukaiyama-type reaction). In this reaction the DNBA salt is preferred usually as stronger acids result in decomposition of the silyl ether. Both acyclic ejco-enolates and 2-silyloxy furan derivatives were seen to undergo 1,4 addition with enals in the presence of a catalytic amount of 1 (20 mol %). This latter transformation allows easy entry to enantiomerically enriched butenolides, and has been applied to the s)uithesis of spiculisporic acid (eq 8). 

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