Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites
Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites
复制标题
DOI：
10.1038/nature05553
复制
发表时间：
2007-02-22
期刊：
影响因子：
64.8
通讯作者：
Ishihara, Kazuaki
中科院分区：
文献类型：
--
作者：
Sakakura, Akira;Ukai, Atsushi;Ishihara, Kazuaki
含有卤素原子的多环生物活性天然产物已从许多不同的海洋生物中分离出来（1）。这些天然产物的生物合成似乎是通过碳-碳双键处的亲电卤化反应（2-4）经由类似于质子诱导的烯烃多环化（5-8）的机制引发的。酶如卤代过氧化物酶产生亲电子卤钥离子（或其等同物），其与类聚异戊二烯的末端碳-碳双键反应，对映选择性地诱导产生卤化多环萜类的环化反应。使用对映体选择性卤环化反应是化学合成这些卤代环状萜类化合物的一种可能方式;尽管已经通过使用化学计量的溴化试剂的非对映体选择性卤环化反应合成了几种溴化环状萜类化合物（9-12），但尚未报道由手性促进剂诱导的类异戊二烯的对映体选择性卤环化。在这里，我们报告的对映选择性卤环化的简单聚异戊二烯使用亲核启动子。非手性亲核磷化合物能够促进非对映选择性卤代环化反应，以优异的产率得到卤代环状产物。此外，手性亚磷酰胺促进简单的聚异戊二烯与N-碘代琥珀酰亚胺的对映选择性卤代环化，得到碘化环状产物，对映体过量和非对映体过量高达99%。据我们所知，这是第一个成功的例子，对映体选择性卤多环化的聚异戊二烯。
Polycyclic bio-active natural products that contain halogen atoms have been isolated from a number of different marine organisms(1). The biosynthesis of these natural products appears to be initiated by an electrophilic halogenation reaction at a carbon - carbon double bond(2-4) via a mechanism that is similar to a proton-induced olefin polycyclization(5-8). Enzymes such as haloperoxidases generate an electrophilic halonium ion ( or its equivalent), which reacts with the terminal carbon - carbon double bond of the polyprenoid, enantioselectively inducing a cyclization reaction that produces a halogenated polycyclic terpenoid. Use of an enantioselective halocyclization reaction is one possible way to chemically synthesize these halogenated cyclic terpenoids; although several brominated cyclic terpenoids have been synthesized via a diastereoselective halocyclization reaction that uses stoichiometric quantities of a brominating reagent(9-12), the enantioselective halocyclization of isoprenoids induced by a chiral promoter has not yet been reported. Here we report the enantioselective halocyclization of simple polyprenoids using a nucleophilic promoter. Achiral nucleophilic phosphorus compounds are able to promote the diastereoselective halocyclization reaction to give a halogenated cyclic product in excellent yields. Moreover, chiral phosphoramidites promote the enantioselective halocyclization of simple polyprenoids with N-iodosuccinimide to give iodinated cyclic products in up to 99% enantiomeric excess and diastereomeric excess. To the best of our knowledge, this is the first successful example of the enantioselective halopolycyclization of polyprenoids.