Retipolides – Unusual Spiromacrolactones from the Mushrooms Retiboletus retipes and R. ornatipes

Abstract

AbstractMushrooms of the genus Retiboletus contain the retipolides A–D (1, 6–8), unusual 14‐membered spiromacrolides with a biphenyl ether linkage. The structures of these metabolites suggested a biogenetic sequence starting from retipolide E (16), which could furnish the unique 2(3H)‐oxepinone unit of retipolide C (7) via an oxidative enlargement of the 4‐hydroxyphenyl ring. A subsequent O/C‐acyl shift would then lead to the cyclopenta[c]pyran system of retipolide A (1). The proposed precursor 16 was synthesized and subsequently detected in the fungal extract in addition to the probable biosynthetic intermediates butyrolactone II (13), tyrosol (14), and secoretipolide E (15). The structural elucidation of retipolide A (1) was accomplished after transformation into a methoxyfulvene derivative 2a, and the absolute (R) configuration of 1 was assigned by a single‐crystal X‐ray analysis of the corresponding (S)‐sec‐butoxyfulvene analogue 2b. Some samples of R. retipes/ornatipes contained isoretipolide A (9), an isomer of 1 with a highly strained 12‐membered lactone ring incorporating two C,C‐coupled 4‐hydroxyphenyl units. A comparison of the CD spectrum of retipolide A (1) with those of the other retipolides and isoretipolide A (9) indicates that all of these macrolides possess R configuration. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)