Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in an intramolecular Diels-Alder reaction
Total synthesis of (+)-aloperine. Use of a nitrogen-bound silicon tether in an intramolecular Diels-Alder reaction
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DOI：
10.1021/ja983013
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发表时间：
1999-02-03
影响因子：
15
通讯作者：
Schwink, L
中科院分区：
文献类型：
--
作者：
Brosius, AD;Overman, LE;Schwink, L
报道了苦豆碱（1）、N-甲基苦豆碱（2）和N-烯丙基苦豆碱（3）的对映选择性全合成。合成策略的中心元素是分子内Diels-Alder反应，其中环粘附分子通过N-甲硅烷基胺键连接。I的全合成从市售的3-羟基哌啶盐酸盐（54）和（R）-哌啶酸（35）通过9个分离和纯化的中间体进行。该合成足够有效，可以容易地制备克量的（+）-苦豆碱（1）。早期的探索性研究还引入了一种方便的方法，用于用磺酰胺单元束缚环加成配偶体，以实现乙烯基磺酰胺的分子内Diels-Alder环加成：45 -> 46。
Enantioselective total syntheses of aloperine (1), N-methylaloperine (2), and N-allylaloperine (3) are reported. The central element of the synthetic strategy is an intramolecular Diels-Alder reaction in which the cycloaddends are tethered by a N-silylamine linkage. The total synthesis of I proceeds from commercially available 3-hydroxypiperidine hydrochloride (54) and (R)-pipecolinic acid (35) by way of nine isolated and purified intermediates. The synthesis is sufficiently efficient that gram quantities of(+)-aloperine (1) can be readily prepared. Early exploratory studies also introduced a convenient method for tethering cycloaddition partners with a sulfonamide unit to realize the intramolecular Diels-Alder cycloaddition of a vinylsulfonamide: 45 --> 46.