Sakakura Akira, Ukai Atsushi, Ishihara Kazuaki
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan.
Nature. 2007 Feb 22;445(7130):900-3. doi: 10.1038/nature05553.
Polycyclic bio-active natural products that contain halogen atoms have been isolated from a number of different marine organisms. The biosynthesis of these natural products appears to be initiated by an electrophilic halogenation reaction at a carbon-carbon double bond via a mechanism that is similar to a proton-induced olefin polycyclization. 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, 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.
已从多种不同的海洋生物中分离出含有卤素原子的多环生物活性天然产物。这些天然产物的生物合成似乎是通过类似于质子诱导的烯烃多环化的机制，在碳 - 碳双键处发生亲电卤化反应开始的。诸如卤过氧化物酶之类的酶会生成亲电卤鎓离子（或其等价物），该离子与聚异戊二烯的末端碳 - 碳双键反应，对映选择性地引发环化反应，生成卤化多环萜类化合物。使用对映选择性卤环化反应是化学合成这些卤化环状萜类化合物的一种可能方法；尽管已经通过使用化学计量的溴化试剂的非对映选择性卤环化反应合成了几种溴化环状萜类化合物，但尚未报道由手性促进剂诱导的类异戊二烯的对映选择性卤环化反应。在此，我们报道了使用亲核促进剂对简单聚异戊二烯进行对映选择性卤环化反应。非手性亲核磷化合物能够促进非对映选择性卤环化反应，以优异的产率得到卤化环状产物。此外，手性亚磷酰胺与N - 碘代琥珀酰亚胺一起促进简单聚异戊二烯的对映选择性卤环化反应，得到对映体过量和非对映体过量高达99%的碘化环状产物。据我们所知，这是类异戊二烯对映选择性卤多环化反应的首个成功实例。
