Spirocycloisomerization of tethered alkylidene glycocyamidines: Synthesis of a base template common to the Palau'amine family of alkaloids
Spirocycloisomerization of tethered alkylidene glycocyamidines: Synthesis of a base template common to the Palau'amine family of alkaloids
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DOI：
10.1002/anie.200462069
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Harran, PG
中科院分区：
文献类型：
--
作者：
Garrido-Hemandez, H;Nakadai, M;Harran, PG
1993年，Scheuer、Kinnel及其同事描述了从海洋海绵Stylotella aurantium提取物中分离出的一种抗菌成分帕劳胺（1）的结构解析。[1]这种物质抑制细菌和真菌的生长。它具有在体外阻断刺激的T细胞增殖的额外能力，但对静息淋巴细胞仍然相对无害。这种免疫抑制特性的机制尚不清楚。作为制备可用于其探索的分子的一步，我们在此描述了一种新的螺环化过程--其具有支持palauamine及其结构相关物axinellamine（2）[2]和massadine（3）[3]的合成的潜力。多环双胍1-3是更大的生物碱家族的成员，其精确的生物合成来源是推测的主题。[1b直到最近，咪唑4被认为是该集团的可能原料。[4a新的观察挑战了这一想法。[6]然而，从综合的角度来看，[7]根据4铸造结构1-3仍然是一个有用的练习。子结构4可以在多周期1-3内追踪两次（方案1）。在每种情况下，单体是头对头取向的，其中键a和B形成共同的嵌入环戊烷。从该核发出的取代基的相对立体化学在1-3方面不同。这样的空间变化提供了一个理由保守的事件，氧化后或在环戊烷环的形成过程中，可以发散到观察到的环系统，那些类似的构成，但交替连接。[4a]我们在本文中报告了一种核心底物类型，其易于在适用于所有三种靶标的螺环化中形成键a。方案2详细说明了在帕劳胺的情况下反应如何进行。这个具体的例子与一般的
In 1993 Scheuer, Kinnel, and co-workers described the structural elucidation of palau amine (1), an antimicrobial principle isolated from extracts of the marine sponge Stylotella aurantium.[1] This substance inhibits both bacterial and fungal growth. It has the additional ability to block stimulated T-cell proliferation in vitro, yet remains relatively innocuous toward resting lymphocytes. The mechanism (s) underlying this immunosuppressive property is not known. As a step toward the preparation of molecules useful for its exploration, we describe herein a new spirocyclization process—one with potential to support a synthesis of palauamine as well as its constitutional relatives axinellamine (2)[2] and massadine (3)[3].Polycyclic bisguanidines 1–3 are members of a larger alkaloid family whose precise biosynthetic origin is a subject of speculation.[1b, 4, 5] Until recently, imidazole 4 was considered likely feedstock for the group.[4a, c] New observations challenge that idea.[6] However, from the synthetic perspective,[7] casting structures 1–3 in terms of 4 remains a useful exercise. Substructure 4 can be traced twice within polycycles 1–3 (Scheme 1). In each instance, the monomers are oriented head-to-head with bonds a and b forming a common embedded cyclopentane. The relative stereochemistries of substituents that emanate from this core differ in 1–3. Such spatial variations offer a rationale for how conserved events, initiated oxidatively after or during formation of the cyclopentane ring, could diverge to the observed ring systems—those similarly constituted but alternately linked.[4a] We report herein a core substrate type prone to form bond a in a spirocyclization applicable to all three targets. Scheme 2 details how the reaction could operate in the palau amine case. This specific example parallels the general