Total Synthesis of Silyl-Protected Early Intermediates of Polyketide Biosynthesis

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作者：

K Krohn，A Vidal，HT Tran-Thien，U Fl?Rke，A Bechthold，G Dujardin，I Green

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摘要：

The ketal- or dithioketal-protected isocoumarins 1518 gave the corresponding 1-naphthols 2126 in their reactions with the acetoacetate (10) or pentane-2,4-dione (19) dianions and the acetone monoanion. Subjection of the dithioketal-protected ester 28 to BakerVenkataraman reaction conditions led to the 8-deoxy tautomeric, protected forms 29/30 of the early decaketide antibiotic intermediate 2b. However, the dithioketal protecting groups could not be removed without destruction of the molecule. Consequently the silyl-protected unstable early tri- and tetracyclic decaketide biosynthesis intermediates 37a, 37b, and 38a (precursors of angucycline and anthracycline antitumor antibiotics) were prepared through silylation of 33a and 33b, to afford 34a and 34b, and subsequent treatment with acetylacetone dianion. The ultimate synthetic goal, the silyl-protected 2,3-dialkylated naphthol derivative 41, was achieved by selective elongation of the bottom chain of the bis-silyl-protected methyl ester 36 with acetylacetone dianion.

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关键词：

Natural products Biosynthesis Total synthesis Reactive intermediates Antibiotics Anthracycline precursor &shy Polyketides