Studies toward the efficient synthesis of polyacetylenic natural products and analogues : Polyacetylene 구조를 가진 천연물과 그 동류 화합물의 효율적인 합성 연구

국문 초록 (Abstract)

인접한 3개의 삼중결합을 가진 천연물인 (S)-17-hydroxy-15E-octadecen-9,11,13-triynoic acid ((E)-15,16-dihydrominquartynoic acid, 3) 를 시중에서 쉽게 구입 가능한 trimethylsilyl acetylene 과 8-bromooctanoic acid 로 부터 합성하였다. (E)-15,16-dihydrominquartynoic acid 3 은 KB, LNCaP, SW626에서 강한 생리활성을 나타내었다. Terminal acetylen을 trialkylsilyl group으로 protecting 해서, 불안정한 terminal acetylene을 거치지 않고 bromoacetylene으로 바로 바꾸었다. 이렇게 얻은 bromoacetylene을 triisopropyl acetylene과 Pd-Cu catalyzed cross coupling을 수행하여 성공적인 결과를 얻었다. 이 프로토콜은 여러 개의 삼중결합을 가진 다양한 천연물과 천연물이 아닌 화합물의 합성에 응용될 수 있다.

다국어 초록 (Multilingual Abstract)

A new total synthesis of the antitumor alkaloid, (±)-pancratistatin has been accomplished from readily available known starting material in 17 steps with an overall yield of 5.8%. We have also developed an efficient synthetic pathway to the intermediate compound in racemic route with enantioselectivity, thus showing that our approach could yield the enantioselective synthesis of (+)-pancratistatin. Our approach differs significantly from other previous studies in some aspects. First, we utilized the Claisen rearrangement/Ireland-Claisen rearrangement as a key step to construct the A and C rings with the appropriate stereochemistry. In addition, the problem of installing six contiguous stereogenic centers in the C ring was successfully addressed in our approach, primarily due to the use of a cyclic sulfate elimination reaction.
Natural histrionicotoxin, a substance isolated from the skins of the "arrow poison frog" and its fully hydrogenated derivative, perhydrohistrionicotoxin (pHTX), have been the subject of synthetic investigation because of their important neurophysiological activity and a unique framework. In this work, we could obtained the appropriately functionalized compound with azaspiro[5,5]undecane ring system as a formal precursor of perhydrohistrionicotoxin. An important feature of this synthesis is the creation of a stereogenic center by using Ireland-Claisen Rearrangement, and Ring-Closing Metathesis (RCM).