Biosynthesis of Sespendole

Abstract

Sespendole is the first reported fungal metabolite having an indolosesquiterpene core structure. Materials and Methods Spectroscopic MeasurementsThe patterns and rates of incorporation of 13 C-labeled 1 were determined using 13 C NMR spectra obtained using a JEOL EX-270 (270 MHz) spectrometer and the 13 C-15 N coupling of 15 N-labeled 1 was determined from the 13 C NMR spectra obtained using a Varian Inova 600 (600 MHz). Materials Sespendole ProductionA stock culture of strain P. terrestris FKA-25 was grown on slants adjusted to pH 6.0 and containing 0.1% glycerol, 0.02% yeast extract (Oriental Yeast Co.), 0.02% MgSO 4 ·7H 2 O, 0.08% KH 2 PO 4 , 0.08% K 2 HPO 4 , 0.02% KCl, 0.02% NaNO 3 and 1.0% agar. The slants were incubated at 27°C and stored in tubes sealed with screw caps at 27°C. Prior to production of 1, P. terrestris ORIGINAL ARTICLE Biosynthesis of SespendoleRyuji Uchida, Hiroshi Tomoda, Satoshi Ō mura

Synthetic Study on Sespendole, an Indole Sesquiterpene Alkaloid: Stereo­controlled Synthesis of the Sesquiterpene Segment Bearing All Requisite Stereogenic Centers

“…25 In conclusion, we achieved synthesis of the key sesquiterpene intermediate 2 bearing all requisite stereocenters of sespendole (1). The synthetic features involved (1) highly stereoselective [2,3]-Wittig rearrangement to obtain the C3 quaternary stereogenic center in the densely functionalized substrate and (2) isomerization of the epoxide with a low-valent titanium reagent without H 2 O in a highly stereoselective manner. Our synthetic route of key intermediate 2 could be applicable to stereocontrolled construction of the related indole diterpenes.…”

“…Gratifyingly, [2,3]-Wittig rearrangement 17 was found to give us the desired product with the proper stereochemistry, as shown in Scheme 3. Thus, the rearrangement of stannylmethyl ether 11, derived from the allylic alcohol 4, was treated with n-BuLi in THF to provide the desired product 12 as a single diastereomer in 79% yield.…”

“…Thus, the rearrangement of stannylmethyl ether 11, derived from the allylic alcohol 4, was treated with n-BuLi in THF to provide the desired product 12 as a single diastereomer in 79% yield. In order to prevent the protonation of the in situ produced a-oxy lithium species before [2,3]-Wittig rearrangement, the inverse addition of the substrate was crucial for achievement of a high yield. The structural assignment was verified by NMR analysis as shown in Figure 1.…”

Drimane-Related Merosesquiterpenoids, a Promising Library of Metabolites for Drug Development

“…35) [347,351]. Feeding experiments revealed that sespendole was formed from the condensation of a farnesyl residue and an anthranilate-derived indole-3-glycerol phosphate residue [356]. Sespendole (544) was isolated from Pseudobotrytis terrestris FKA-25 as an inhibitor of lipid droplet formation in macrophages [353][354][355].…”

Bacterial Synthesis of Diverse Indole Terpene Alkaloids by an Unparalleled Cyclization Sequence

“…Initially, a BLAST analysis annotated the gene product of xiaE as an unknown membrane protein. Interestingly, xiaE homologues are found in various fungal and bacterial terpenoid biosynthesis gene clusters, [16] for example for paspaline biosynthesis; [17] however, their true function has been overlooked or misinterpreted. A more detailed domain analysis indicated that XiaE is functionally related to a recently described homologue that plays a key role in the biosynthesis of the fungal meroterpenoid pyripyropene A.…”