Enantioselective total synthesis of the marine toxin (-)-gymnodimine employing a Barbier-type macrocyclization.
Enantioselective total synthesis of the marine toxin (-)-gymnodimine employing a Barbier-type macrocyclization.
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DOI：
10.1002/anie.200903432
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发表时间：
2009
影响因子：
16.6
通讯作者：
Lee, Changsuk
中科院分区：
文献类型：
--
作者：
Kong, Ke;Romo, Daniel;Lee, Changsuk
裸二胺（1，图 1）是螺环亚胺海洋毒素家族的成员，最初是从新西兰海岸收集的牡蛎中分离出来的。总体结构最初由 Yasumoto 于 1995 年报道 [i]，随后 Munro 和 Blunt 报道了通过还原的 N-酰化衍生物的 X 射线晶体学分析阐明的相对和绝对立体化学。[ii] 这种毒素由甲藻 Karenia selliforms（以前称为 Gymnodinium selliforme）产生，在神经毒性贝类中毒的小鼠生物测定中具有活性。[iii] 最近，研究发现，裸二胺可使神经元对冈田酸的作用敏感 [iv]，并且有证据表明它与肌肉烟碱乙酰胆碱受体的子集结合。[v] 分离出另外两种类似物，其区别仅在于 C17–C18 烯烃上的烯丙基氧化，并分别命名为裸二胺 B (2) 和 C (3)。[vi] 这个不断增长的螺环亚胺毒素家族的其他成员包括羽衣藻毒素、[vii] 螺内酯、[viii] 翼藻毒素、[ix] prorocentrolide、[x] 和螺原中心胺。[xi]这一含螺环的海洋毒素家族激发了人们强烈的合成努力[xii]，最终实现了羽衣藻毒素和翼藻毒素的完全或正式合成。[xiii] 然而，裸二胺的全合成仍然存在[xiv]与该家族的其他成员相比，裸二胺看似更简单的结构隐藏了微妙的、具有挑战性的结构元素，特别是已知的不稳定丁烯内酯，增加了全合成的挑战。[xv]在此，我们描述了(−)-裸二胺的第一个全合成，它为最终生产用于裸二胺检测的酶联免疫吸附测定（ELISA）以及进一步的作用模式研究提供了合适的中间体。[xvi]
Gymnodimine (1, Figure 1) is a member of the spirocyclic imine family of marine toxins initially isolated from oysters collected off the coast of New Zealand. The gross structure was initially reported by Yasumoto in 1995 [i] and subsequently, Munro and Blunt reported the relative and absolute stereochemistry elucidated through X-ray crystallographic analysis of a reduced, N-acylated derivative.[ii] This toxin is produced by the dinoflagellate Karenia selliforms (formerly Gymnodinium selliforme) and is active in the mouse bioassay for neurotoxic shellfish poisoning.[iii] Recently, gymnodimine was found to sensitize neurons to the effects of okadaic acid [iv] and there is evidence that it binds to a subset of muscle nicotinic acetylcholine receptors.[v] Two additional analogs, differing only by an allylic oxidation at the C17–C18 olefin, were isolated and named gymnodimine B (2) and C (3), respectively.[vi] Other members of this growing family of spirocyclic imine toxins include the pinnatoxins,[vii] spirolides,[viii] pteriatoxins,[ix] prorocentrolide,[x] and spiroprorocentrimine.[xi]This family of spirocyclie-containing marine toxins has inspired intense synthetic efforts [xii] that have culminated in total or formal syntheses of the pinnatoxins and pteriatoxins.[xiii] However, the total synthesis of gymnodimine still remains elusive.[xiv] The seemingly simpler architecture of gymnodimine compared to other members of this family conceals subtle, challenging structural elements, in particular the known labile butenolide adding to the challenge of a total synthesis.[xv] Herein, we describe the first total synthesis of (−)-gymnodimine that provides suitable intermediates for eventual production of an enzymelinked immunosorbent assay (ELISA) for gymnodimine detection and also further mode of action studies.[xvi]
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影响因子：
15
作者：
Hao, Junliang;Matsuura, Fumiyoshi;Iwashita, Takashi
通讯作者：
Iwashita, Takashi
影响因子：
5.2
作者：
Kong, K;Moussa, Z;Romo, D
通讯作者：
Romo, D
影响因子：
1.8
作者：
BAILEY, WF;PATRICIA, JJ;WANG, W
通讯作者：
WANG, W
影响因子：
3.6
作者：
GIOVANNINI, A;SAVOIA, D;UMANIRONCHI, A
通讯作者：
UMANIRONCHI, A
影响因子：
3.6
作者：
BAILEY, WF;PUNZALAN, ER
通讯作者：
PUNZALAN, ER