Decarboxylative Claisen Rearrangement Reactions: Method Development and Applications to Total Synthesis

我们希望开展研究，开发一种我们发明的新方法，通过形成新的碳/碳键，将小的含碳分子片段连接在一起，制成更大的分子片段。我们发现的新工艺首先是通过不饱和醇与含磺酸基的羧酸结合形成易于制造的酯来将碎片连接在一起。在弱碱和硅烷化试剂存在的情况下加热酯时，重排/裂解过程随着二氧化碳的释放而发生。在我们的过程中，新的碳/碳键的形成具有高选择性，并使空间要求高的大体积碳片段能够连接在一起。我们的目标是评估转化与底物中一些不同的化学基团的兼容性，并看看化学是否与羧酸酯旁边的磺酰基以外的基团起作用。我们还计划寻找可能另外含有杂原子的底物。最后，我们希望使用我们的新反应合成几种具有生物活性的天然产物。这些分子靶标之一是从海洋生物中分离出来的抗癌化合物家族的成员。另一种是一种有效的止痛和消炎化合物，而第三种是与维生素D有关的天然产品，后者有可能成为结核病的新疗法。

We wish to carry out research to develop a new way we have invented of joining together small carbon-containing molecular pieces to make larger ones by making new carbon/carbon bonds. The novel process we have discovered involves firstly connecting together the pieces by forming easy-to-make esters through the combination of unsaturated alcohols with carboxylic acids containing a sulfonyl group. On heating the esters in the presence of a weak base and a silylating agent a rearrangement/fragmentation process takes place with the evolution of carbon dioxide. The formation of new carbon/carbon bonds in our process takes place with high selectivity, and enables the joining together of sterically demanding, bulky carbon fragments.We aim to assess the compatibility of the transformation with a number of different chemical groupings within the substrates, and to see if the chemistry works with groups other than sulfonyl next to the carboxylic esters. We plan also to look at substrates which may additionally contain heteroatoms.Finally, we wish to synthesise several biologically active natural products using our new reaction. One of these molecular targets is a member of a family of anti-cancer compounds isolated from a marine organism. Another is a potent analgesic and anti-inflammatory compound, whilst a third is a natural product related to vitamin D which has potential as a novel treatment for tuberculosis.