3-AMINO-5-HYDROXYBENZOIC ACID IN ANTIBIOTIC BIOSYNTHESIS - XI - BIOLOGICAL ORIGINS AND SEMISYNTHESIS OF THIONAPHTHOMYCINS, AND THE STRUCTURES OF NAPHTHOMYCIN-I AND NAPHTHOMYCIN-J

Fermentations of Streptomyces sp. E/784 produce low levels of the nove l C-30 alkylthio-substituted ansamycin antibiotics naphthomycins J (9) and I(10), in addition to the more abundant C-30 hydroxylated analogu es actamycin (1) and naphthomycin D (2) and C-30 chlorinated analogues naphthomycins H (3) and A (4). The addition of N-acetyl-L-cysteine to the fermentation medium substantially increases the production of the thionaphthomycins J and I at the expense of their chloro analogues H and A. Other thiols and thiol progenitors are similarly utilised, incl uding N-acetyl-L-cysteine methyl ester which affords the known naphtho mycin F (8) and its novel 2-demethyl homologue (7). The formation of t hioansamycins from chloroansamycins and thiols in vivo is probably non -enzymic since similar conversions can be effected in vitro.