Syntheses and structural confirmations of members of a heterocycle-containing family of labdane diterpenoids.
Syntheses and structural confirmations of members of a heterocycle-containing family of labdane diterpenoids.
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DOI：
10.1002/anie.201208412
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发表时间：
2013-01-28
影响因子：
16.6
通讯作者：
Njardarson, Jon T.
中科院分区：
文献类型：
--
作者：
Mack, Daniel J.;Njardarson, Jon T.
Labdanes [1] 是一大类结构多样的二萜类天然产物，具有一系列生物活性。 [2]在过去的几年中，已经报道了有趣的新拉丹烷天然产物，其含有由亚甲基单元与反式十氢萘核心隔开的五元杂环（1-6，[3]方案1）。这些拉丹烷天然产物从未被合成，并且大多数结构尚未被明确指定。例如，1 和 2 相对于十氢萘核心的 C12 立体化学是未知的。 3 和 6 之间的关系特别有趣，因为它们共享相同的十氢萘核心，但在 C12-C14 处存在对映体关系。鉴于我们对二萜类天然产物合成的承诺，[4] 对合成 2, 5-二氢呋喃结构的贡献，[5] 以及对合成用于生物筛选目的的新的和独特的天然产物集合的普遍兴趣，这些目标似乎非常适合。我们设想可以通过从杜松子中提取大量获得这些目标结构的手性十氢萘核心，并且我们的乙烯基环氧乙烷环扩展反应将是获得这些目标结构的良好匹配。 2, 1和2的5-二氢呋喃核心，然后可以进一步氧化为内酯4和二醇3和6。 [6]详细说明这些计划的逆合成分析如方案 2 所示。用于我们合成的容易获得且廉价的起始材料是通信酸，它们通常作为二烯异构体（E-、Z- 和微通信酸）的混合物从杜松的浆果中分离出来。 [7]其他针叶树种也以不同的比例产生通信酸，但常见的杜松子可以提供高达 57% 的通信酸，从而使它们成为我们合成计划的理想来源。 [8]
Labdanes [1] are a large and structurally diverse class of diterpenoid natural products exhibiting a range of biological activities.[2] In the last few years, interesting new labdane natural products containing five membered heterocycles separated by a methylene unit from the trans-decalin core have been reported (1–6,[3] Scheme 1). These labdane natural products have never been synthesized and most of the structures have not been unambiguously assigned. For example, the C12 stereochemistry of 1 and 2 relative to the decalin core is not known. The relationship between 3 and 6 is particularly interesting, as they share an identical decalin core, but an enantiomeric relationship at C12–C14. Given our commitment to the synthesis of diterpenoid natural products,[4] contributions toward the synthesis of 2, 5-dihydrofuran architectures,[5] and general interest in synthesizing new and unique collections of natural products for biological screening purposes, these targets seemed well suited.We envisioned that the chiral decalin core of these target structures could be accessed in large quantities by extraction from juniper berries, and that our vinyl oxirane ring expansion reaction would be a good match for accessing the 2, 5-dihydrofuran cores of 1 and 2, which could then be further oxidized to lactone 4 and diols 3 and 6.[6] A retrosynthetic analysis detailing these plans is shown in Scheme 2. The readily available and inexpensive starting materials for our synthesis would be the communic acids, which are typically isolated as a mixture of diene isomers (E-, Z-, and mirceo-communic acids) from the berries of Juniperis communis.[7] Other coniferous species also produce the communic acids in various ratios, but the common juniper berries can provide up to 57% by mass of the acids, thus making them an ideal source for our synthetic plans.[8]
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
Njardarson, Jon T.