Malladi Drugs & Pharmaceuticals Limited, Research & Development Centre, Chennai 600 124, TN, India; Organic Chemistry Division, CSIR-Central Leather Research Institute, Chennai 600 020, TN, India; Division of Microbiology and Cancer Biology, Entomology Research Institute, Loyola College, Chennai 600 034, TN, India.
Organic Chemistry Division, CSIR-Central Leather Research Institute, Chennai 600 020, TN, India.
Bioorg Med Chem Lett. 2014 Jul 15;24(14):3057-63. doi: 10.1016/j.bmcl.2014.05.027. Epub 2014 May 20.
Enantiomerically pure N-alkylated β-amino alcohols 1a, 1a', 1c, 1c', 1d, 1d', 1e and 1e', with ee 100% have been synthesized from phenylpropanolamines 2. Effect of the neighboring chiral environment on the newly formed chiral center has been studied experimentally and concluded that the newly formed chiral center's absolute configuration is opposite to the adjacent (α- or β-) chiral environment. The antimicrobial activity of the synthesized β-amino alcohols were screened using in vitro disc diffusion method and variable antimicrobial activities were shown for 1a, 1a', 1c, 1c', 1d, 1d', 1e &1e' and amongst them 1d &1d' exhibited significant activity against bacteria and fungi. In silico studies revealed all the synthesized β-amino alcohols 1a-e and 1a'-e' have shown good binding energies ranging from -7.38 to -6.09 kJ/mol towards the target receptor DNA topoisomerase IV and 1d' has shown maximum binding energy -7.38 kJ/mol.
已从苯丙醇胺 2 合成了对映体纯的 N-烷基化β-氨基醇 1a、1a'、1c、1c'、1d、1d'、1e 和 1e',ee 值为 100%。实验研究了相邻手性环境对新形成的手性中心的影响,得出结论:新形成的手性中心的绝对构型与相邻的(α-或β-)手性环境相反。采用体外圆盘扩散法筛选了所合成的β-氨基醇的抗菌活性,结果表明 1a、1a'、1c、1c'、1d、1d'、1e 和 1e'对细菌和真菌具有不同的抗菌活性,其中 1d 和 1d'对细菌和真菌表现出显著的活性。计算机研究表明,所有合成的β-氨基醇 1a-e 和 1a'-e'与靶标受体 DNA 拓扑异构酶 IV 的结合能均在-7.38 至-6.09 kJ/mol 之间,其中 1d'的结合能最大,为-7.38 kJ/mol。