Paraherquamide family

The structures of asperparalines A (123), B (124), and C (125) were determined to be spiro compounds made up of an A -methyl succinimide and a cyclopent[f]indolizine having an A methyl amide bridge. Another structural characteristic of asperparalines is a bicyclo[2,2,2]diazaoctane core, and various compounds, such as those of the paraherquamide family mentioned in the following section, contain the same core in their structures. However, all these compounds have an indole moiety in their structures so, it is of great interest that asperparalines have no indole part in their structures. 

The paraherquamide family and other related compounds cited in the... 

In 2002, Williams reviewed studies on total synthesis and biosynthesis of the paraherquamide family, with a focus on the biological Diels-Alder construction of the bicyclo[2,2,2]diazaoctane ring system [119]. 

The structurally related alkaloid marcfortine, first described by Polonsky et al. in 1980 [35] is rendered from two isoprene units, tryptophan and pipecolic acid. The structures of the members of this family of mold metabolites are presented in Fig. 4. The paraherquamides differ with respect to substitution and oxygenation in the proline ring and the prenyiated oxindole ring paraherquamide B is the simplest member of the paraherquamide family, being comprised of the amino adds proline, tryptophan, and two isoprene units. 

Finally, Zeeck et al. isolated the interesting substances aspergamide A and B from Aspergillus ochraceus [36]. These metabolites, including VM55599, are the only natural members of the paraherquamide family that do not have a spiro-ring system but instead a 2,3-disubstituted indole-derived system. 

It is also interesting to note that -methylproline residues can be found in several peptide antibiotics such as bottromycin, scytonemin A, roseotoxin B in addition to several members of the paraherquamide family. Arigoni and Kellen-berger [41 ] have recently shown that the methyl group in the )3-methylproline in bottromycin, a metabolite of Streptomyces bottropenis, is derived from S-adeno-sylmethionine via methylation of proline (Scheme 19) and have proposed a radical mechanism for this reaction. 

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