Structural studies on rhodilunancins A and B.

Abstract

Antitumor antibiotics rhodilunancins A and B were isolated from a culture of Streptomyces violaceus var. lunanensis var. n. No. 1289 by acidic acetone extraction of mycelia and purified by silica gel chromatography.Rhodilunancin A is identical to cosmomycin A. Rhodilunancin B is identical to cosmomycin B (=rhodomycin Y). Both antibiotics exhibited activities against Gram-positive bacteria and inhibition on DNA synthesis of P353 leukemia cell in vitro.In the course of our screening for new antitumor antibiotics, a Streptonryces strain, Streptomyces vioaceus var. lunanensis var. n. No. 1289 isolated from soil sample collected at Lunan county, Yunnan province, was found to produce two anthracycline antibiotics, rhodilunancins A (I) and B (II) (Fig. 1). Strain No. 1289 was cultured in a fermentor containing a medium of the following composition: soluble starch 1.5%, dextrin 1.5%, glucose 1.5%, soybean meal 1.2%, peptone 0.5% yeast extract 0.5%, (NH4)2SO4 0.25 %, NaCl 0.2 %, KH2PO4 0.02 %, CaCO3 0.3 %, MgSO4 0.02 %. The cultivation was carried out at 28°C for 4 days.The antibiotics in the mycelia were extracted with acidic acetone. The extracts were concentrated in vacuo to remove acetone and reextracted with ethyl acetate. The basic glycosides were separated from the aglycone by extraction with aqueous acid (pH 3). The acidic solution was adjusted to pH 8

The Anthracyclinic Complex Retamycin, 1. Structure Determination of the Major Constituents

“…On the basis of these chemical and spectroscopic findings, we can propose the structures for retamycins E1 [1] and E2 [2] as shown. The structures are identical with those published for rhodilunancins A and B (13), which in turn have been found to be identical with cosmomycins A and B (14).…”

“…Fractions of Rf 0.22 (tic in the same solvent) yielded, after evaporation and crystallization from Cyclohexane, pure 1 as a red powder with mp 145-148°[lit. (13) 140-142°].…”

“…Retamycin E2 [2],-Further elution with the same solvent, evaporation of fractions of Rf 0.19 and crystallization from Cyclohexane produced pure 2 as a dark red powder with mp 146-150°[lit. (13) 154-156°].…”

Elucidating the Sugar Tailoring Steps in the Cytorhodin Biosynthetic Pathway

“…Accordingly, large scale fermentation of the Streptomyces sp. SCSIO 1666/Δ trdA1 DH mutant strain enabled the isolation and elucidation of five anthracycline compounds, namely cytorhodins X ( 1 ) and Y ( 2 ), cosmomycins A ( 3 ) and B ( 4 ), − and iremycin ( 5 ) (Figure A) . All of these compounds were elucidated by HRESIMS, 1 H, and 13 C NMR spectroscopic methods and comparisons with previously reported literatures.…”

Bioprospecting of Actinobacterial Diversity and Antibacterial Secondary Metabolites from the Sediments of Four Saline Lakes on the Northern Tibetan Plateau

“…Cosmomycin C revealed a similar fragmentation pathway with cosmomycin D, except for the first product, 1059.1 (-114), which was in correspondence with the middle sugar in one trisaccharide chain lacking a hydroxyl group. It is worth noting that cosmomycins have been previously reported to possess antibacterial activities against gram-positive bacteria, show significant antitumor activity against human tumors, and can induce the differentiation of Friend leukemia cells [75,76]. A recent study has also suggested that cosmomycin A inhibits the growth of Plasmodium falciparum 3D7 cells with an IC 50 value of 2.8 nM [77].…”