Aranotin biosynthesis

Cyclo(L-[U- C]phenylalanyl-L-phenylalanine) is incorporated into BDA in 19.9% yield, in cultivation for 48 hr in Asp. terreus (141). In contrast, the cyclo L,D and D,D isomers are not incorporated. Further, the isolation of cis-3,6-bibenzyl-3,6-bis(methylthio)piperazine-2,5-dione (71), mp 291-293°C, [a]54g — 122°, from Asp. terreus (142) suggests that the sulfur atoms are introduced in an early stage of aranotin biosynthesis, as in gliotoxin biosynthesis. 

Arene oxides and their oxepin tautomers play a role in the biosynthesis of some microbial metabolites, e.g., the sulfur-containing antibiotics gliotoxin (345),188 dehydrogliotoxin (346),189 apoarontin (347),190 aranotin (348),191... 

Aranotins and Sirodesmin.—ctc/o-(l Phenylalanyl-L-seryl) is an efficient and intact precursor for gliotoxin (114) (cf. Vol. 10, p. 27). Bisdethiobis(methylthio)-acetylaranotin (115) is related to gliotoxin in the biosynthesis of this metabolite, it is believed that ring-opening of an arene oxide las (116)1 occurs, followed by further epoxidation and cyclization, as in the biosynthesis of gliotoxin (114).2... 

If the analogy with gliotoxin biosynthesis is extended, c7cto(L-phenylalanyl-L-phenylalanyl) should be a precursor for all members of the aranotin group, but, so far, this point has not been tested experimentally. 

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