Biogenetically inspired approach to the Strychnos alkaloids.: Concise syntheses of (±)-akuammicine and (±)-strychnine
Biogenetically inspired approach to the Strychnos alkaloids.: Concise syntheses of (±)-akuammicine and (±)-strychnine
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DOI：
10.1021/ja010935v
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发表时间：
2001-08-22
影响因子：
15
通讯作者：
Martin, SF
中科院分区：
文献类型：
--
作者：
Ito, M;Clark, CW;Martin, SF
吲哚生物碱（+/-）-akuammicine（2）的线性合成通过一种新的反应序列完成，仅需要10个步骤，从市售的起始原料。该方法的特征在于串联乙烯基曼尼希加成和分子内杂狄尔斯-阿尔德反应，以从容易获得的乙酰胆碱6快速组装五环杂嵌合体衍生物8。氧化8的E环得到内酯9，内酯9转化为去甲酰基geissoproteinine（11）。随后的阐述11到2的影响，涉及连续氧化和碱诱导的骨骼重组的biomiphilic模式的转变。然后将这些策略的变体应用于C（18）羟基化的阿库米星衍生物36的合成。因为36以前已经通过四个步骤转化为士的宁（1），它的制备构成了这种复杂生物碱的简洁，正式的合成。
A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroychimboid derivative 8 from the readily available hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganization. A variation of these tactics was then applied to the synthesis of the C(18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.