Total Synthesis of the Marine Natural Product Hemiasterlin by Organocatalyzed α-Hydrazination
Total Synthesis of the Marine Natural Product Hemiasterlin by Organocatalyzed α-Hydrazination
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DOI：
10.1002/chem.201702812
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发表时间：
2017-09-18
影响因子：
4.3
通讯作者：
Lindel, Thomas
中科院分区：
文献类型：
--
作者：
Lang, Jan Hendrik;Jones, Peter G.;Lindel, Thomas
介绍了一种高效合成具有细胞毒性的海洋多肽半海星素的方法。四甲基-色氨酸部分通过吲哚的叔异戊二烯化组装，然后通过具有优异的对映选择性的空间拥挤的醛的高产率有机催化的α-肼化。2-溴-N-乙基吡啶四氟硼酸盐（BEP）介导的肽偶联完成了合成，这是第一种不使用手性助剂的方法。一种新的酚型重排的吲哚系统发生时，进行二羟基化的3-叔异戊二烯吲哚Mitsunobu条件。
An efficient synthesis of the potently cytotoxic marine peptide hemiasterlin is presented. The tetramethyl-tryptophan moiety is assembled by tert-prenylation of indole, followed by the high-yielding organocatalyzed alpha-hydrazination of a sterically congested aldehyde with excellent enantioselectivity. 2-Bromo-N-ethylpyridinium tetrafluoroborate (BEP)-mediated peptide coupling completes the synthesis, being the first approach that does not employ chiral auxiliaries. A novel phenonium-type rearrangement of the indole system occurred when subjecting dihydroxylated 3-tert-prenylindole to Mitsunobu conditions.