Sporidesmin biosynthesis

Kirby, G. W., and M. J. Varley Synthesis of Tryptophan Stereoselectively Labelled with Tritium and Deuterium in the P-Methylene Group the Steric Course of Hydroxylation in Sporidesmin Biosynthesis. J. C. S. Chem. Comm. 833-834 (1974). 

A number of microbial metabolites whose biosynthesis has been studied are (at least formally) derived from a di- (or tri-)peptide echinulin and benzodiazepine alkaloids (both referred to already), gliotoxin, mycelianamide/ sporidesmin, and the /3-lactam antibiotics. In the case of the last mentioned, in spite of extensive work and the accumulation of a wealth of detail on the fates of the individual atoms in the precursor amino-acids, the mechanism of ring formation remains obscure. 

An important hypothesis concerning the function of N-hydroxy-amino acids has been formulated recently by Ottenheijm 126). There are indications that the metabolism of several types of non-protein amino acids such as N-hydroxyamino acids, dehydroamino acids and a-substituted amino acids is connected with the process of oxidation of amino acids or peptides. Hence it is suggested that N-hydroxy amino acids play an important role in the biosynthesis of dehydroamino acids 18 natural antiviral, antifungal or antibacterial products (as e.g. glio-toxin) 127) and some other fungal metabolites as sporidesmine 126), as sketched in Scheme 16. 

The metabolic steps leading from tryptophan to sporidesmin have not been investigated in any detail, although one might expect a close correspondence with gliotoxin biosynthesis. For example, formation of the fused pyrrolidine system could involve an intermediate epoxide (26) analogous to... 

The chaetocins and verticillins constitute an extensive series of tryptophan metabolites (see Table II) having a close structural relationship with the sporidesmins. However, two indole rings have been linked oxidatively, and this process, rather than epoxidation, is presumably responsible for closure of the pyrrolidine ring there is precedence for this in the biosynthesis of, for... 

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