Studies in organic synthesis

本世纪在复杂天然产物和相关化合物的全合成方面的最终挑战是能够揭穿这样的神话，即这些化合物在制药工业中不是经济上可行的目标（S。巴兰2010，75，4657）。 因此，我们目前正在探索一个强大的合成环加成反应的快速建设天然和非天然类固醇和高级萜类化合物的一般性。在我们的实验室中发现的这种新颖的基于阴离子的环加成反应通过将两个结构单元（单环或双环）结合在一起以完全控制手性而在一步或两步中产生多环化合物。这种新的合成策略具有高度收敛性，可用于选定的天然产物的靶向合成以展示其价值，随后用于工业上发现新的生物活性化合物的多样性导向合成。 为了证明这种新策略的潜力，我们最近报道了哇巴因的第一个全合成（Angew. Chem.Int.Ed.2008，47，1272）。这种复杂的心脏活性类固醇最近被确定为人类内源性激素，与高血压有直接联系。这一新的化学知识导致了高血压研究项目的制定和内源性哇巴因生物合成途径的研究。我们还完成了Hippurchanol的全合成，Hippurchanol是一种类固醇，可能导致开发基于新机制的抗癌药物。我们还致力于合成抗癌剂马钱子碱、神经毒素Batrachotoxin、抗癌剂紫杉醇和相关类似物。 我们也有一个新的兴趣，研究新的方面的立体电子效应与构象和反应性的大量的有机官能团。

The ultimate challenge of this century in total synthesis of complex natural products and related compounds is to be able to debunk the myth that such compounds are not economically viable targets in the pharmaceutical industry (S. Baran. J. Org. Chem. 2010, 75, 4657). Accordingly, we are currently exploring the generality of a powerful synthetic cycloaddition reaction for the rapid construction of natural and non-natural steroids and higher terpenoids. This novel anionic-based cycloaddition reaction discovered in our laboratory leads to polycyclic compounds in one or two-steps by combining two building blocks (mono or bicyclic) with complete control of chirality. Being highly convergent, this new synthetic strategy can be used for target-oriented synthesis of selected natural products to demonstrate its value and later on for diversity oriented synthesis for the discovery of new biological active compounds in industry. In order to demonstrate the potential of this novel strategy, we have recently reported the first total synthesis of Ouabain (Angew. Chem. Int. Ed. 2008, 47, 1272). This complex cardioactive steroid recently being identified as a human endogenous hormone has a direct link with hypertension. This novel chemical knowledge has led to the elaboration of research project on hypertension and on the study of the biosynthetic pathway of endogenous Ouabain. We have also completed the total synthesis of Hippuristanol, a steroid that could lead to develop novel-mechanism-based anticancer drugs. We are also working on the synthesis of the anticancer agent, Bruceantin, the neurotoxin Batrachotoxin, the anticancer agent Taxol and related analogues. We have also a renewed interest to investigate novel aspect of stereoelectronic effects in relation with conformation and reactivity of a large number of organic functional groups.