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

Abstract Mushrooms 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(3 H )‐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)