Medicinal Chemistry Laboratory, GVK Biosciences Private Limited, Plot No.28, IDA, Nacharam, Hyderabad 500 076, AP, India.
Eur J Med Chem. 2011 May;46(5):1803-12. doi: 10.1016/j.ejmech.2011.02.039. Epub 2011 Feb 23.
We report herein an efficient enantioselective synthesis of SPF32629A and SPF32629B through one-pot enantioselective reduction and protecting-group-free regioselective O-acylation strategy. The absolute configuration of the enantiomerically pure isomers was established by Mosher ester analysis. The inhibitory potencies of the synthesized compounds were assayed in vitro against a panel of microorganisms and against A549 human lung adenocarcinoma cell line. Compounds 2, 11 and 12 displayed moderate to potent antibacterial activity against all the tested strains and compounds 7, 8, 2, 11 and 12 exhibited significant cytotoxicity in a dose-dependent manner with an IC50 values ranging from 2.92 to 4.14 μg/ml and 8-11 μM.
我们通过一锅对映选择性还原和无保护基区域选择性 O-酰化策略，高效地合成了 SPF32629A 和 SPF32629B。通过 Mosher 酯分析确定了对映体纯异构体的绝对构型。合成化合物的抑制活性通过体外实验进行了评估，针对一系列微生物和 A549 人肺腺癌细胞系进行了检测。化合物 2、11 和 12 对所有测试菌株均表现出中等至较强的抗菌活性，化合物 7、8、2、11 和 12 表现出显著的细胞毒性，呈剂量依赖性，IC50 值范围为 2.92 至 4.14 μg/ml 和 8-11 μM。
