Kirst H A, Toth J E, Wind J A, Debono M, Willard K E, Molloy R M, Paschal J W, Ott J L, Felty-Duckworth A M, Counter F T
J Antibiot (Tokyo). 1987 Jun;40(6):823-42. doi: 10.7164/antibiotics.40.823.
A large series of C-23-modified derivatives of 5-O-mycaminosyltylonolide were synthesized, in which the C-23 hydroxyl group was replaced by halo, aryl ether or thioether, azido, amino or dialkylamino substituents via SN2 displacement reactions. The majority of derivatives possessed excellent in vitro activity against a variety of aerobic and anaerobic bacteria. While some of the compounds treated experimental infections in rodents by parenteral administration, none showed any significant efficacy or bioavailability after oral dosing. Novel rearrangement products were obtained from some of the reactions; these were identified as 13,23-cyclopropyl-12,22-exomethylene and 13,23-cyclopropyl-12-alkoxy derivatives.
合成了一系列5-O- mycaminosyltylonolide的C-23修饰衍生物，其中通过SN2取代反应将C-23羟基替换为卤素、芳基醚或硫醚、叠氮基、氨基或二烷基氨基取代基。大多数衍生物对多种需氧菌和厌氧菌具有优异的体外活性。虽然一些化合物通过肠胃外给药治疗了啮齿动物的实验性感染，但口服给药后均未显示出任何显著疗效或生物利用度。从一些反应中获得了新型重排产物；这些产物被鉴定为13,23-环丙基-12,22-亚甲基和13,23-环丙基-12-烷氧基衍生物。
