Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 12. Synthesis of (-)-Platynecine.
Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 12. Synthesis of (-)-Platynecine.
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DOI：
10.1021/jo961919x
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发表时间：
1997-01
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影响因子：
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通讯作者：
S. Denmark;D. Parker;J. Dixon
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文献类型：
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作者：
S. Denmark;D. Parker;J. Dixon
吡咯里西啶类生物碱由于其结构多样性和有趣的生物学性质而成为有吸引力的合成目标。1我们已经开发了一种高度通用的方法，通过使用硝基烯烃的串联[4+ 2]/[3+ 2]环加成来构建吡咯里西啶框架。2该反应在几种吡咯烷类化合物的合成中起到了关键的作用，包括（-）-hastanecine（1），3（-）-rosmarinecine（2），4和（+）-crotanecine（3），5图1。这些合成的一个显著特点是使用对映体纯的乙烯基醚来控制目标分子的绝对构型。此外，[3+ 2]环加成的分子内性质以及系链的长度和构型用于控制关键中心的相对构型。因此，在（-）-迷迭香碱（2）中，C（1）、C（7a）和C（7）之间的全顺式关系在[3+ 2]环加成中建立。这种相同的关系（也是绝对意义上的）存在于（-）-扁果芸香碱（4）中，这意味着在C（6）处的脱氧（而不是转化4）将提供从共同的合成中间体获得这种更简单的吡咯里西啶同系物的途径。本文介绍了以（-）-迷迭香碱的高级中间体为原料，经四步反应合成（-）-桔梗碱的方法。（-）-Platynecine（4）于1935年首次从千里光中分离得到，是几种吡咯里西啶生物碱的necine碱部分，包括Platyphyllin、6 neoplatyphiline、7 bulgarsenine、8 nemorensine、9 retroisosenine、8 mugediifoline、10和ligularinine。[11]已经报道了外消旋形式的扁果芸香碱（4）的合成[12]以及三次对映体富集形式的合成。13
Pyrrolizidine alkaloids are attractive targets for synthesis due to their structural diversity and interesting biological properties. 1 We have developed a highly versatile method for the construction of pyrrolizidine frameworks through the use of the tandem [4+ 2]/[3+ 2] cycloaddition of nitroalkenes. 2 This reaction has served admirably as the key step in the synthesis of several pyrrolizidines including (-)-hastanecine (1), 3 (-)-rosmarinecine (2), 4 and (+)-crotanecine (3), 5 Figure 1. A remarkable feature of these syntheses is the use of an enantiomerically pure vinyl ether to control the absolute configuration of the target molecules. Additionally, the intramolecular nature of the [3+ 2] cycloaddition and the length and configuration of the tether are used to control the relative configuration of the critical centers. Thus, in (-)-rosmarinecine (2), the all-cis relationship between C (1), C (7a), and C (7) is established in the [3+ 2] cycloaddition. This same relationship (also in an absolute sense) exists in (-)-platynecine (4), which implied that deoxygenation (instead of inversion4) at C (6) would provide access to this simpler pyrrolizidine congener from a common synthetic intermediate. This paper describes the synthesis of (-)-platynecine in four steps from an advanced intermediate in the (-)-rosmarinecine synthesis.(-)-Platynecine (4) was first isolated in 1935 from Senecio Platyphyllusis6 and is the necine base portion of several pyrrolizidine alkaloids including platyphyllin, 6 neoplatyphilline, 7 bulgarsenine, 8 nemorensine, 9 retroisosenine, 8 mulgediifoline, 10 and ligularinine. 11 The synthesis of platynecine (4) has been reported in racemic form12 as well as three times in enantiomerically enriched form. 13