Synthesis of the carbocyclic core of zoanthenol: Implementation of an unusual acid-catalyzed cyclization
Synthesis of the carbocyclic core of zoanthenol: Implementation of an unusual acid-catalyzed cyclization
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DOI：
10.1002/anie.200700430
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Stoltz, Brian M.
中科院分区：
文献类型：
--
作者：
Behenna, Douglas C.;Stockdill, Jennifer L.;Stoltz, Brian M.
Zoanthamine生物碱复杂而优雅的结构吸引了合成化学家十多年。[1，2]尽管许多研究小组已经发表了对动物黄胺的研究成果，[1]这类药物中唯一完成的合成是Miyashita等人在2004年合成的去甲动物黄胺[3]（图1）。动物黄胺具有许多生物活性，其中盐酸去甲动物黄胺的抗氧化活性突出显示了这一点。[4]我们对zoanthamines的兴趣被zoanthenol（1）激发了，[5]它是唯一拥有芳香环的家族成员。Zoanthenol保留了Zoanthamines的主要立体化学挑战，同时提供了探索独特的逆合成可能性的机会。在这里，我们描述了一个不寻常的SNо环化形成zoanthenol的碳环核心。通过我们实验室最近开发的不对称烷基化方法，可以实现这种核心结构的不对称立体选择性路线。[6]美国
The complex and elegant architecture of the zoanthamine alkaloids has captivated synthetic chemists for well over a decade.[1, 2] Although numerous research groups have published efforts toward the zoanthamines,[1] the only completed synthesis of any member of this class was that of norzoanthamine by Miyashita et al. which appeared in 2004 [3](Figure 1).The zoanthamines exhibit a host of biological activities highlighted by the anti-osteoporotic activity of norzoanthamine hydrochloride.[4] Our interest in the zoanthamines was piqued by zoanthenol (1),[5] the sole family member possessing an aromatic Aring. Zoanthenol retains the major stereochemical challenges of the zoanthamines, while offering the opportunity to explore unique retrosynthetic possibilities. Herein, we describe an unusual SNо cyclization to form the carbocyclic core of zoanthenol. An asymmetric stereoselective route to this core structure is enabled by asymmetric alkylation methodology recently developed in our laboratories.[6]