Carneiro Vânia M T, Avila Carolina M, Balunas Marcy J, Gerwick William H, Pilli Ronaldo A
Institute of Chemistry, University of Campinas (UNICAMP), C.P. 6154, CEP 13084-971 Campinas, São Paulo, Brazil.
J Org Chem. 2014 Jan 17;79(2):630-42. doi: 10.1021/jo402339y. Epub 2014 Jan 9.
The interface between synthetic organic chemistry and natural products was explored in order to unravel the structure of coibacin A, a metabolite isolated from the marine cyanobacterium cf. Oscillatoria sp. that exhibits selective antileishmanial activity and potent anti-inflammatory properties. Our synthetic plan focused on a convergent strategy that allows rapid access to the desired target by coupling of three key fragments involving E-selective Wittig and modified Julia olefinations. CD measurements and comparative HPLC analyses of the natural product and four synthetic stereoisomers led to determination of its absolute configuration, thus correcting the original assignment at C-5 and unambiguously establishing those at C-16 and C-18. Additionally, we synthesized coibacin B on the basis of the assignment of configuration for coibacin A.
为了解开从海洋蓝藻cf. Oscillatoria sp.中分离出的具有选择性抗利什曼原虫活性和强大抗炎特性的代谢产物柯巴辛A的结构，对合成有机化学与天然产物之间的界面进行了探索。我们的合成计划集中在一种汇聚策略上，该策略通过涉及E-选择性维蒂希反应和改良朱利亚烯烃化反应的三个关键片段的偶联，能够快速获得所需目标产物。对天然产物以及四种合成立体异构体进行圆二色性测量和比较高效液相色谱分析，从而确定了其绝对构型，因此纠正了C-5位的原始构型归属，并明确确定了C-16和C-18位的构型。此外，我们根据柯巴辛A的构型归属合成了柯巴辛B。
