Georgiadis M P, Couladouros E A, Delitheos A K
Chemistry Laboratories, Agricultural University of Athens, Greece.
J Pharm Sci. 1992 Nov;81(11):1126-31. doi: 10.1002/jps.2600811117.
The synthesis of several derivatives of 2H-pyran-3(6H)-ones and their Michael adducts is described. Phenylthio, benzenesulfonyl, p-acetylaminobenzenesulfonyl, and p-bromophenyl substituents are beneficial for activity against gram-positive bacteria. 2-[4-(Phenylthio)phenyl]-2-methyl-6-methoxy-2H-pyran-3(6H)-one (8a) showed a minimum inhibitory concentration of 1.56 micrograms/mL against Staphylococcus aureus ATCC 2593, and 2-[4-(phenylthio)phenyl]-2-methyl-6-[(p-nitrobenzoyl)oxy]-2H-pyran-3 (6H)-one (9) showed a minimum inhibitory concentration of 0.75 microgram/mL against Streptococcus sp. C203M. In general, derivatives of 6-hydroxy-2H-pyran-3(6H)-ones with substituents at C-2 and C-6 showed significant activity against gram-positive bacteria. More specifically, the bulkier the C-2 substituent, the greater the antibacterial activity. Michael adducts of thiols (13) showed activity, which may be due to a retro-Michael reaction. In conclusion, the alpha,beta-enone system is essential for the activity of 6-hydroxy-2H-pyran-3(6H)-ones, and the size and nature of substituents at C-2 are associated with antimicrobial activity.
本文描述了几种2H-吡喃-3(6H)-酮衍生物及其迈克尔加成物的合成。苯硫基、苯磺酰基、对乙酰氨基苯磺酰基和对溴苯基取代基对革兰氏阳性菌具有抗菌活性。2-[4-(苯硫基)苯基]-2-甲基-6-甲氧基-2H-吡喃-3(6H)-酮(8a)对金黄色葡萄球菌ATCC 2593的最低抑菌浓度为1.56微克/毫升，2-[4-(苯硫基)苯基]-2-甲基-6-[(对硝基苯甲酰基)氧基]-2H-吡喃-3(6H)-酮(9)对链球菌C203M的最低抑菌浓度为0.75微克/毫升。一般来说，在C-2和C-6位带有取代基的6-羟基-2H-吡喃-3(6H)-酮衍生物对革兰氏阳性菌具有显著活性。更具体地说，C-2位取代基越大，抗菌活性越强。硫醇的迈克尔加成物(13)具有活性，这可能是由于逆迈克尔反应。总之，α,β-烯酮体系对6-羟基-2H-吡喃-3(6H)-酮的活性至关重要，C-2位取代基的大小和性质与抗菌活性相关。
