Bellomo P, Brufani M, Marchi E, Mascellani G, Melloni W, Montecchi L, Stanzani L
J Med Chem. 1977 Oct;20(10):1287-91. doi: 10.1021/jm00220a012.
3-Aminotolypomycinoes and 3,16-diamino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to tolypomycinone, obtained by mild hydrolysis of the antibiotic tolypomycin Y.3-Amino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to 16,17-dihydrotolypomycinone. In vitro microbiological tests showed high antibacterial activity in compounds obtained by the addition of primary amines, which must be unbranched in the alpha position to the nitrogen atom to position 3 of the naphthoquinone ring. The relationship between structure and activity is described, and evidence is presented that hydrogen bonding between the amino NH bonded to C3 and the amide CO of tolypomycinone is very important for biological activity.
3-氨基托利霉素和3,16-二氨基-16,17-二氢托利霉素酮是通过将伯胺和仲胺添加到由抗生素托利霉素Y温和水解得到的托利霉素酮中形成的。3-氨基-16,17-二氢托利霉素酮是通过将伯胺和仲胺添加到16,17-二氢托利霉素酮中形成的。体外微生物学试验表明,通过添加伯胺得到的化合物具有高抗菌活性,该伯胺在萘醌环3位的氮原子的α位必须是无支链的。描述了结构与活性之间的关系,并提供证据表明与C3相连的氨基NH与托利霉素酮的酰胺CO之间的氢键对生物活性非常重要。