A new anthracycline antibiotic N-formyl-13-dihydrocarminomycin.

Abstract

Sir: During the course of our screening for inducers of mouse myeloid leukemic cell (M1)1) differentiation, we have recently isolated four active components related to the carminomycins from the cultured broth of an actinomycete. The isolation and structures of these components are reported in this paper. The producing organism of the active substances was isolated from a soil sample collected in Satsumacho, Kagoshima. On the basis of taxonomic studies, it was identified as a strain of Actinomadura roseoviolacea. The strain was cultivated in jar fermentors at 37°C for 4 days containing a medium consisting of 2.5% glucose, 1.5% soybean meal, 0.2 yeast extract and 0.4% CaCO3. After centrifuging the cultured broth (25 liters), the mycelial cake was extracted with acetone. The combined acetone extract was concentrated to a small volume and extracted with ethyl acetate. The organic layer was concentrated and subjected to Sephadex LH-20 column chromatography and eluted with methanol to give three pigment fractions. The first band material was further separated into three red compounds A, B and C by preparative silica gel thin-layer chromatography with a solvent system of chloroform methanol acetic acid (8: 2: 0.1). The second band material was further subjected to silica gel (treated with phosphoric acid) column chromatography using a chloroform methanol system to give red compound D. Further purification of these compounds A, B, C and D was achieved by Toyopearl HW40F chromatography with methanol. From the third band, a non-glycosidic compound E was obtained by silicic acid column chromatography using chloroform and recrystallized from chloroform to yield red needles The general appearance of the 1H NMR of F was similar to that of 13-dihydrocarminomycinone except at the 7 position. The molecular formula C20H18O7 (m/z 370.10354, calcd. 370.10194) of E was determined by high resolution mass spectroscopy. The structure of E is proposed by these data as shown in Fig. 1. The pigments A, B and C were confirmed tc be identical with carminomycin II, carminomycin I2 ) and 13-dihydrocarminomycin3) , respectively, by their UV, IR, mass and 1H NMR spectrometries. The pigment D is produced as red needle crystals C27H29O11N, nip 180~185°C, [a]25D+111 (c 0.1, in MeOH+0.1 N HCl), 2max (in MeOH) (E1%1cm) 235 (605), 252 (474), 293 (134), 480 (200), 492 (228), 579 (59), Amax (in MeOH+0.1 N NaOH) (E1%1cm) 240 (619), 290 (123), 555 (213), 595 (185), m/z 566 (M+Na, FD-MS). On acid hydrolysis with 0.1 N HCl at 100°C for 10 minutes, the pigment D yielded 13-dihydrocarminomycinone. The 1H NMR spectrum (Fig. 2) of D showed that there are signals assigned to the N-formyldaunosamine moiety at o 5.72 (1'-H, d, J=3.4 Hz), 1.80 (2'-H, overlapped with 8-H), 1.97 (2'-H, dd, J=5.0, 14.0 Hz), 4.26 (3'-H, Fig. 1. The structure of E.

Cite this paper

@article{Nakagawa1983ANA, title={A new anthracycline antibiotic N-formyl-13-dihydrocarminomycin.}, author={Masanori Nakagawa and Yumiko Hayakawa and Hiroki Kawai and Kenkichi Imamura and Hiroshi Inoue and Atsushi Shimazu and Hiroyuki Seto and Noboru Otake}, journal={The Journal of antibiotics}, year={1983}, volume={36 4}, pages={457-8} }