Patent / 1964
Fermentative production of tetracycline or chlortetracycline
A sterilized medium (300 1) contg. starch 60, peanut meal 3, CaCO3 4, (NH4)2SO4 4.5, corn steep liquor 4, dibenzylethylenediaminediacetate (I) 2.5 g. and lard oil 1.8% by vol./l. was inoculated with suspended spores of Streptomyces lusitanus, and fermented under submerged aerobic conditions, with stirring at 26.degree. for 120 hrs. The mycelium is sepd. from the broth (acidified with dil. H2SO4) by filtration. I (0.3 g./l.) is added, and the pH adjusted to 8.2 with 10% NH4OH. The ppt. of the I complex of chlortetracycline (II) thus obtained is removed by filtration, suspended in 6300 cc. of 2-ethoxy- or 2-methoxyethanol, and 864 g. NaCl and coned. HCl are added with strong stirring until the pH is 0.45. After 12 hrs. of the stirring the crystals are filtered, washed with 2-ethoxyethanol, iso-PrOH, and then H2O. The dried II-HCl thus obtained weighs 1753 g., m.p. 223-31, [.alpha.]20 -220 (c 1.5, 1: 1 HCONMe2-MeOH). A similar fermentation in a broth previously freed from Cl- yielded the I-tetracycline complex-HCl salt. Brit. 936,314; 5 pp. See preceding abstract.