Studies on the development of new, short, and practical synthetic methods for the synthesis of isocarbacyclin

本研究建立了一种新颖、短步、收敛、实用的异卡布霉素合成方法，采用一锅三步法，包括乙烯醚形成、Claisen重排、双环[3.3.1]-骨架的反应，不依赖于该领域以往的任何想法，与前列腺素合成的思路基本相同。本研究提供的新方法可以先构建含长一碳的同丙烯基ω -链的环戊酮骨架，然后引入短二碳的α -链，为双环[3.3.1]-骨架提供前体。该方法需要(4S)-4-（o -叔丁基二甲基硅基）-环戊烯-2-烯-1-酮作为重要的起始手性化合物，其对映体在PG合成中是众所周知的起始原料。因此，换句话说，(4S)-异构体被赋予了迄今为止尚未经历过的重要价值。以(S)-1,2-（o -异丙基）甘油为原料，经过一系列常规反应（7步），以20克为单位高效合成了与ω - 3链相对应的手性合成物，每步产率为80-95%。可通过乙烯醚生成烯丙基叔醇来提供将提交至一锅三步法的双环[3.3.1]-骨架的前体。由于某些原因，我们希望用于这种转化的反应应该不含汞盐，经过几次尝试，我们成功地开发了一种新的、通用的方法，用于从各种烯丙醇（包括叔型）合成乙烯醚。

This research has established a novel, short-step, convergent, and practical method for the synthesis of isocarbacyclin featuring a one-pot, three-step process involving vinyl ether formation, Claisen rearrangement, and en reaction to give bicyclo [3.3.1]-backbone, which is not relying on any previous idea in this field that is principally the same as that for prostaglandin synthesis. The new method provided in this research can construct cyclopentenone framework bearing the homoallylic omega-chain longer by one-carbon at first followed by the introduction of the alpha-chain shorter by two-carbon to furnish the precursor for the bicyclo [3.3.1]-backbone. The method required (4S)-4-(O-tert-butyldimethylsilyl)-cyclopent-2-en-1-one as an important starting chiral compound, the antipode of which has been well-known starting material in PG synthesis. In other words, therefore, (4S)-isomer is given significant value which has not been experienced so far.A chiral synthon corresponding to the homoallylic omega-chain has been synthesized efficiently from (S)-1,2-(O-isopropylidene) glycerol in twenty-gram scale and 80-95% yield for each step through a series of routine reactions (7 steps).A precursor for the bicyclo [3.3.1]-backbone to be submitted to the one-pot, three-step process can be provided from an allylic tert-alcohol by vinyl ether formation. We hoped that a reaction to be used in this transformation should be free from mercury salts for some reasons and, after several attempts, has succeeded in developing a new, general method for the synthesis of vinyl ether from various allylic alcohols including tert-versions.