Paraherquamide from Penicillium

Prenyl rearrangement. Efficient total syntheses of 3-ferf-prenylated indole alkaloids employ prenyl shifts fi om C2, which can be considered biomimetic, since it was shown by Williams that the biosynthesis of paraherquamide A (199) from Penicillium sp. proceeds via tert-prenyl shift fi om C2 to C3 starting from precursors like 198 (Scheme 39) [2, 165], in agreement with earlier proposals by Barrow [166] and by Gorst-Allman [167] for the biosynthesis of roquefortine. 

Marcfortines A (165), B (166), and C (167) were isolated from the mycelium of Penicillium roqueforti by Polonsky and coworkers in 1980 (Fig. (36)) [116, 117]. Marcfortines contain a piperidine ring instead of a pyrrolidine ring in paraherquamides and sclerotiamide. Biogenetically, the basic skeleton of 165 is clearly derived from a dioxopiperazine formed from tryptophan and pipecolic acid. In 1999, Kuo and coworkers elucidated the biosynthetic pathway of the pipecolic acid moiety of 165 [H8]. 

The origin of the )8-methylproline moiety present in paraherquamide A and several congeners has recently been investigated. Examination of the absolute stereochemistry of paraherquamide A, which possesses the (S)-absolute stereochemistry at C-14, led Williams et al. to speculate that the methylated proline may be derived from L-isoleucine as opposed to proline and S-adenosylmethio-nine (SAM) and this possibility was experimentally tested in Penicillium felluta-num (ATCC 20841) as shown in Fig. 5 [39]. The position of incorporation in paraherquamide A was determined using NMR and the percentage of the labeled amino acid incorporated was also determined using NMR. 

In the course of isotopic labeling studies aimed at examining the origin of the isoprene units in the paraherquamide structure, Williams et al. discovered an unexpected stereochemical distribution of the geminal methyl groups derived from DMAPP [42]. These workers carried out feeding experiments in Penicillium... 

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