Preparation of substituted phenyl pyrroles through the metabolism of tryptophan analogues

Biochemical and Biophysical Research Communications
1968.0

Abstract

We have recently shown (Lively et al., 1967) by the use of C14-labeled precursors that tryptophan, I, is a direct precursor of the antifungal substance pyrrolnitrin, II. Pyrrolnitrin, 3-chloro-4-(2'-nitro-3'-chlorophenyl)-pyrrole (Imanaka et al., 1965a; Nakano et al., 1966), is produced by several species of pseudomonads (Imanaka et al., 1965b); in our laboratory it is available from Pseudomonas aureofaciens ATCC 15926. This organism when grown on a complex or synthetic medium is capable of converting either endogenous or exogenous tryptophan to pyrrolnitrin. Thus, the addition of 500 µg/ml of dl-tryptophan to the culture mentioned resulted in increasing the yield of pyrrolnitrin from 50 to 100 µg/ml of broth. For the multi-step process, this represents a minimum yield of 8%, based on exogenous dl-tryptophan. We have now been able to add the tryptophan analogues, dl-6-fluorotryptophan (III) and dl-7-methyltryptophan (IV) to fermentations of P. aureofaciens and to recover the pyrrolnitrin derivatives, 3-chloro-4-(2'-nitro-3'-chloro-4'-fluorophenyl)-pyrrole (V) and 3-chloro-4-(2'-nitro-3'-methylphenyl)-pyrrole (VI), respectively. These new substances possess significant antifungal activity.

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