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(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)

New Pulvinic Acid and Phenylalaninol Derivatives from the Mushrooms Retiboletus griseus and R. nigerrimus

“…This is in accord with the known biosynthesis of Lphenylalaninol from L-phenylalanine in cultures of Penicillium brevicompactum [15]. In summary, our investigation of Retiboletus griseus and R. nigerrimus has added four new members to the list of unique metabolites from this genus [2], which underlines the special taxonomic position of Retiboletus in Boletaceae [1]. The tetra acetate was formed by stirring ester 2 (0.8 mg) and a catalytic amount of DMAP in Ac 2 O (1.5 mL) overnight at r. t. After addition of a few drops of water, the mixture was extracted with Et 2 O, the solvent was removed under reduced pressure, and the tetra acetate was dried in vacuo.…”

“…The supposed position within Retiboletus on behalf of molecular data [1] remains to be proved. During our investigations of these two species, we were unable to detect any retipolides, the characteristic metabolites of R. retipes/ornatipes and R. flavoniger [2].…”

“…Isolation and structure elucidation of retiboletic acid (1) and methyl retiboletate (2) Retiboletus griseus (Frost) Manfr. Binder & Bresinsky is a fairly common mushroom of oak-hickory forests in eastern North America.…”

“…Whereas the first three species are characterized by the occurrence of retipolides [2], the metabolites of R. griseus and R. nigerrimus remained unknown. We have now carried out a chemotaxonomic survey of the latter two species, which resulted in the detection of a new pulvinic acid in these fungi, accompanied by two phenylalaninol derivatives in R. nigerrimus.…”

Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists

“…[72] First, the molecular formula was obtained from EIMS. Next, structural fragments were assembled and combined from COSY and HMBC data, whereas the relative configuration was determined from NOE and proton-proton coupling constants.…”