Streptogramines and method for preparing same by mutasynthesis

摘要

Streptogramin B derivs. of formula (I) are new, in which R2 and R4 = H or Me; R3 = H or OH; X = CO, CHOH or CH2; R1 = 2-thienylmethyl, 2-naphthylmethyl or a gp. of formula (i); for meta derivs., A,C,D,E = H; B = halo; mono- or di-alkylamino; ether or thioether gp.; 1-3C alkyl; or trihalomethyl; for para derivs., A, B, D, E = H; C = halo; NRaRb; opt. substd. N-pyrrolidinyl; ether or thioether gp.; acyl; alkoxycarbonyl; 1-6C alkyl; alkylthiomethyl; aryl; or trihalomethyl; Ra and Rb = H, 1-4C alkyl (if one is Me, the other must be Et), alkyl (3-4C cycloalkyl)methyl, opt. substd. 3-4C cycloalkyl or 1-4C alkenyl (if one is alkenyl the other cannot be Me or cycloalkyl); for meta-para derivs., A ,D, E = H, B is as defined for meta derivs. but not trihalomethyl; and C is halo; NH2 (opt. substd. by 1 or 2 alkyl, provided that B is not Cl, Br or opt. substd. allyl) ; ether or thioether gp.; 1-6C alkyl; or trihalomethyl; for ortho-para derivs., B, E, D = H; A=C=Me. Also claimed is prodn. of streptogramins by culturing an appropriate microorganism having a modification in a gene involved in biosynthesis of streptogramin gp. B precursors, in a medium contg. a new precursor (other than the one whose synthesis is being affected). Further claimed are (inter alia) (1) new DNA contg. specified genes from Streptomyces pristinaespiralis, and (2) certain specified new precursors.