Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Palkalai Nagar, Madurai 625021, India.
Eur J Med Chem. 2010 Jan;45(1):124-33. doi: 10.1016/j.ejmech.2009.09.034. Epub 2009 Oct 1.
A series of novel enantiomerically pure spiroisoxazolidines were synthesized regioselectively by the 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones to (R)-1-(1-phenylethyl)-3-[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones. These compounds have been screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Among the twenty two compounds screened, (3S,4S,5R)-3,4-di(4-methylphenyl)-2-phenyl-7-[(R)-1-phenylethyl]-1-oxa-2,7-diazaspiro[4.5]decan-10-one (3e) was found to possess the maximum activity with MIC of 3.02 microM, being 2.5 times more potent than the first-line anti-TB drug ethambutol. For comparison, a series of ten enantiomerically pure spirooxazolines were also screened, among which (4R,5S)-3,4-bis(4-chlorophenyl)-7-[(R)-1-phenylethyl]-1-oxa-2,7-diazaspiro[4.5]dec-2-en-10-one and (4R,5S)-4-(2-chlorophenyl)-3-(4-chlorophenyl)-7-[(R)-1-phenylethyl]-1-oxa-2,7-diazaspiro[4.5]dec-2-en-10-one were found to display maximum activity with MIC of 3.25 microM.
一系列新型对映体纯的螺环异恶唑烷通过 C-芳基-N-苯基硝酮与（R）-1-（1-苯乙基）-3-[(E)-芳基亚甲基]-四氢-4(1H)-吡啶酮的 1,3-偶极环加成反应区域选择性地合成。这些化合物已通过琼脂稀释法筛选其对结核分枝杆菌 H37Rv（MTB）的体外活性。在所筛选的二十二种化合物中，（3S,4S,5R）-3,4-二（4-甲基苯基）-2-苯基-7-[(R）-1-苯乙基]-1-氧杂-2,7-二氮杂螺[4.5]癸烷-10-酮（3e）显示出最大的活性，MIC 为 3.02 μM，比一线抗结核药物乙胺丁醇强 2.5 倍。作为比较，还筛选了一系列十种对映体纯的螺噁唑啉，其中（4R,5S）-3,4-双（4-氯苯基）-7-[(R）-1-苯乙基]-1-氧杂-2,7-二氮杂螺[4.5]癸-2-烯-10-酮和（4R,5S）-4-（2-氯苯基）-3-（4-氯苯基）-7-[(R）-1-苯乙基]-1-氧杂-2,7-二氮杂螺[4.5]癸-2-烯-10-酮显示出最大的活性，MIC 为 3.25 μM。
