Calicheamicin gamma 1I is a recently discovered diyne-ene--containing antitumor antibiotic with considerable potency against murine tumors. In vitro, this drug interacts with double-helical DNA in the minor groove and causes site-specific double-stranded cleavage. It is proposed that the observed cleavage specificity is a result of a unique fit of the drug and DNA followed by the generation of a nondiffusible 1,4-dehydrobenzene--diradical species that initiates oxidative strand scission by hydrogen abstraction on the deoxyribose ring. The ability of calicheamicin gamma 1I to cause double-strand cuts at very low concentrations may account for its potent antitumor activity.

361ChemInform Abstract Further chemical and physical investigations on the structure of the title compound, in addition to the results of the preceding paper, establish its complete structure as (I).

acetate [ll/3,21 .dihydroxypregna-1,4-dien-3,20-dione 21-acetate] in 10 mL of dry tetrahydrofuran was added via the addition funnel, and the funnel was washed with an additional 10 mL of solvent. TLC indicated the reaction was complete after 2 h and the solution was poured into water and adjusted to a pH of ca. 4 with acetic acid. From this aqueous suspension, 821 mg (2.01 mmol, 78%) of 13 slowly crystallized: mp 187-194 "C (ethyl acetate-cyclohexane); IR 3400,2220, 1750,1665,1615,1605 cm-I; UV 218 nm (c 25 000); NMR 8 7.35 (d, J = 10 Hz, 1 H), 6.28 (dd, The Formation of the Cardenolide 14 from the 1,4-Dien-3-one 13. To a solution of 13 (350 mg, 0.86 mmol) in 50 mL of ethanol was added 2.5 mL of distilled water and 0.5 g of p-toluenesulfonic acid monohydrate. The reaction mixture was refluxed for 16 h, cooled, and diluted with 150 mL of distilled water. The precipitate was filtered, dried, and crystallized from methylene chloridine-ethyl acetatepetroleum ether to yield 205 mg (0.57 mmol, 65%) of cardenolide 14 as the monohydrate: mp 256269 "C; IR 3450,1780,1750,1660,1625, 1660 cm-l; UV 220 nm ( t 21 OOO), 244 (sh, 15 500); NMR (MezS0-d~) 6 7.37 (d, J = 10 Hz, 1 H), 6.17 (dd, J = 10,2 Hz, 1 H), 5.95 (m, 2 H), 4.The isolation and characterization of four new zearalenone-like macrolides and three isocoumarins from an unidentified fungus, Lederle Culture 21640, are reported. By altering the fermentation conditions this organism could be forced to produce curvularin macrolides. X-ray studies on a di-p-chlorobenzoyl derivative of LL-Z1640-1 showed this metabolite to be (4'S,5'S)-4',5'-dihydroxyzearalenone 4-methyl ether.

No abstract

No abstract