（+）-氮杂螺旋酸-1的全合成。复杂分子合成复杂性的展示。
Total synthesis of (+)-azaspiracid-1. An exhibition of the intricacies of complex molecule synthesis.
作者信息
Evans David A, Kvaernø Lisbet, Dunn Travis B, Beauchemin André, Raymer Brian, Mulder Jason A, Olhava Edward J, Juhl Martin, Kagechika Katsuji, Favor David A
机构信息
Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
出版信息
J Am Chem Soc. 2008 Dec 3;130(48):16295-309. doi: 10.1021/ja804659n.
Abstract
The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels-Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.
摘要
海洋神经毒素azaspiracid-1的合成已经完成。各个片段是通过催化对映选择性过程合成的：通过杂Diels-Alder反应得到E环和HI环片段，通过羰基烯反应提供CD环片段，通过Mukaiyama羟醛反应得到FG环片段。随后的片段偶联是通过羟醛和砜阴离子方法完成的。所有形成九元环目标的缩酮化反应都是在平衡条件下利用分子的内在构型采用一种有利构象来完成的。端基异构的EFGHI-砜阴离子与ABCD-醛的最终片段偶联完成了(+)-azaspiracid-1的汇聚合成。
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本文引用的文献
1
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Angew Chem Int Ed Engl. 1998 Dec 31;37(24):3372-3375. doi: 10.1002/(SICI)1521-3773(19981231)37:24<3372::AID-ANIE3372>3.0.CO;2-K.
2
Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method.手性恶唑硼烷催化剂用于羰基化合物的还原：对映选择性催化的新范式及一种强大的新合成方法。
Angew Chem Int Ed Engl. 1998 Aug 17;37(15):1986-2012. doi: 10.1002/(SICI)1521-3773(19980817)37:15<1986::AID-ANIE1986>3.0.CO;2-Z.
3
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Angew Chem Int Ed Engl. 1998 Sep 18;37(17):2354-2359. doi: 10.1002/(SICI)1521-3773(19980918)37:17<2354::AID-ANIE2354>3.0.CO;2-9.
4
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5
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