Patent GB-1244120-A (GB)
Title: Some novel antibiotics and methods for their preparation
IPC: C07G11/00
Filed: 1969-07-25
Abstract: 1,244,120. Antibiotics 289-F, 289-FO and acetyl 289-F. DAIICHI SEIYAKU CO. Ltd. 25 July, 1969 [20 Nov., 1968], No. 37620/69. Heading C2A. Antibiotic (289-F), effective in inhibiting the growth of gram-positive and gram-negative bacteria, which crystallizes as orange-yellow needles from acetonitrile and then methanol, is soluble in methanol, ethanol, acetone, ethyl acetate, benzene, chloroform and acetonitrile and insoluble in aqueous alkaline solution, melting at 211À5-213À0 C., containing the elements carbon, hydrogen and nitrogen in the following proportions by weight: C 67.04%, H 7.12%, N 4.15%, 0 21À69% (by difference), having a U.V. absorption spectrum in a methanol solution in which there are maxima at 244 mÁ (E<SP>1%</SP> 1cm. = 807), 270 mÁ and 434 mÁ (E<SP>1%</SP> 1cm.   = 210), exhibiting absorption in the I.R. region of the spectrum as shown in Fig. 5, when tableted with KBr, at the following frequencies expressed in reciprocal centimetres: 3430, 1620, 1610 and 1585, having an optical rotation 20 [α]<SP>20</SP> D  of +456À7 degrees when dissolved in chloroform at a concentration of 1.5% by weight/volume at 20 C., and reacting bluish purple with nickel acetate at neutral pH; and antibiotic (289-FO), effective in inhibiting the growth of gram-positive and gram-negative bacteria, which crystallizes as yellow needles from ethyl acetate, is very soluble in chloroform, carbon tetrachloride, methanol and ethanol, soluble in ethyl acetate and propyl acetate and insoluble in petroleum ether, melting at 183- 184 C., containing the elements carbon, hydrogen and nitrogen in the following proportions by weight: C 66.90%, H 6.70%, N 3.71%, O 22.69% (by difference), having a U.V. absorption spectrum in a methanol solution in which there are maxima at 244 mÁ (E<SP>1%</SP> 1cm. = 520), 273 mÁ (E<SP>1%</SP> 1cm. = 375) and 430 mÁ. (E<SP>1%</SP> 1cm.  =130), exhibiting absorption in the I.R. region of spectrum as shown in Fig. 4, when tableted in KBr, at the following frequencies expressed in reciprocal centimeters: 3450, 1745, 1650, 1610, 1585, and 1240, having an optical rotation [α]<SP>25</SP> D  of + 316 degrees when dissolved in chloroform at a concentration of 1.5% by weight/ volume at 25 C., and reacting greyish-blue with nickel acetate at neutral pH, are prepared by cultivating a strain, A.T.C.C. 21396, A.T.C.C. 21395, or A.T.C.C. 21397, belonging to Streptomyces phaeoverticillatus var. takatsukiensis under submerged aerobic conditions in an aqueous carbohydrate solution containing nitrogenous nutrient and an anthraquinone sulphonic acid of the formula wherein R is H or a sulphonic acid group or a metal salt of such acid, and recovering the antibiotics from the culture solution. For the production of 289-FO, cultivation is continued for 48-65 hrs. and, for the production of 289-F, cultivation is continued for 70 to 120 hrs. The cultivation may be carried out at 25 to 35 C. with a 0À1 to 2.0% (w./v.) concentration of anthraquinone sulphonic acid or salt thereof. e.g. sodium anthraquinone-2,7-disulphonate. Antibiotic (Acetyl 289.F), effective in inhibiting the growth of gram-positive and gram-negative bacteria, which crystallizes as yellow needles from benzene and then ethyl acetate, is very soluble in benzene, chloroform and pyridine and very slightly soluble in methanol and ethanol, containing the elements carbon, hydrogen and nitrogen in the following proportions by weight: C 66À03%, H 6À56%, N 3À74%, O 23.67% (by difference), having a U.V. absorption spectrum in methanol solution in which there are maxima at 238 mÁ (E<SP>1%</SP> 1cm.  = 603), 270 mÁ(E<SP>1%</SP> 1cm.  = 576)and368-370mÁ (E<SP>1%</SP> 1cm. = 160) exhibiting absorption in the I.R. region of the spectrum as shown in Fig. 6 when tableted with KBr at the following frequencies expressed in reciprocal centimetres: 1748, 1650 and 1242 and having an optical rotation [α]<SP>20</SP> D  of + 246 degrees    2 degrees when dissolved in chloroform at a concentration of 1À5% by weight/volume at 20 C. is prepared by acetylating with acetic anhydride acetyl chloride or ketene the antibiotic 289-F or 289-FO dissolved in an inert solvent at 15 to 50 C. Preferably the reaction solution contains up to 15% by volume of pyridine. The antibiotics may be purified by solvent extraction and column chromatography.