43 マクロライド抗生物質(+)-brefeldin Aの合成研究

概要

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Macrolide antibiotic, (+)-brefeldin A(1) was isolated from fungi (P. cyaneum, P. brefeldianum etc.) and it shows some bacteriocidal and strong phytotoxic activities. Though the synthesis of dl-compound was achieved by Corey et al from cyclopentadiene and the intermediate was prepared by Crabbe et al via different route, optically active (1) is not synthesized yet. We, select the cyclopentanonitrile derivative (24), having all three correct stereochemistry in it's molecule, as the key intermediate. Starting from D-mannitol, lactone-acid (28) was prepared via several steps and cyanomethyl group was introduced into C_2-position, accompanied with decarboxylation. Major isomer (65% of product) was converted to the precursor (38) for intramolecular cyclization in 5 steps and base treatment gave the desired intermdiate (24), stereochemistry of which was confirmed by comparing CD spectrum and [α]_D of cyclopentanone derivatives, obtained from (24) in 6 steps, with reported value. Vinyl group was transformed to acetylenic group and then alkylation gave the product containing necessary side chain at C_5-position. Further studies for the synthesis of (1) is now in progress.
天然有機化合物討論会の論文
1978-08-22