Enantioselective total synthesis of (+)-dibromophakellstatin
Enantioselective total synthesis of (+)-dibromophakellstatin
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DOI：
10.1021/ja034575i
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发表时间：
2003-05-28
影响因子：
15
通讯作者：
Romo, D
中科院分区：
文献类型：
--
作者：
Poullennec, KG;Romo, D
首次实现了（+）-phakellstatin和（+）-dibromophakellstatin的对映选择性全合成。在合成中的关键步骤是二酮哌嗪（S，S）-环（Pro，Pro）通过非对映选择性酰化，分子内Mitsunobu反应，以引入C6缩醛胺，和串联霍夫曼重排/环化，同时引入C10季胺中心，并提供环脲的去对称化。该合成还证明了吡咯并缩胺醛的不寻常的稳定性。重要的是，该策略具有生产生物学研究所需的源自（R，R）-环（Pro，Pro）的phakellstatin衍生物的潜力。类似的成环方案也预期适用于合成帕劳胺。
The first enantioselective total synthesis of (+)-phakellstatin and (+)-dibromophakellstatin was achieved. Key steps in the synthesis were a desymmetrization of the diketopiperazine (S,S)-cyclo (Pro, Pro) via a diastereoselective acylation, an intramolecular Mitsunobu reaction to introduce the C6 aminal, and a tandem Hofmann rearrangement/cyclization to simultaneously introduce the C10 quaternary aminal center and deliver the cyclic urea. The synthesis also demonstrates the unusual stability of pyrrolo aminals. Importantly, this strategy has the potential for producing phakellstatin derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological studies. A similar annulation protocol is also expected to be applicable to the synthesis of palau'amine.