Alkaloid Synthesis Utilizing Cyclic N,O-Acetals
Alkaloid Synthesis Utilizing Cyclic N,O-Acetals
复制标题
利用环状 N,O-缩醛合成生物碱
DOI：
10.1002/chin.200401256
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
C. Kibayashi
中科院分区：
文献类型：
--
作者：
N. Yamazaki;C. Kibayashi
环N， o -缩醛的合成和反应在多环氮杂环的构建和生物碱的合成中具有潜在的用途和通用性。羟基胺与酮羧酸容易缩合的n-酰基- n， o -缩醛通过TiCl4介导的分子内烯烃-胺环化反应转化为2-氮杂环。基于Lewis酸介导的环n -酰基- n， o -缩醛与烯丙基三甲基硅烷的烯丙化，构建6,6 -二取代2-哌啶酮，得到外消旋形式的瓢虫生物碱。该烯丙化反应是用含(R)-2-（1-氨基乙基）苯酚作为手性助剂的环n -酰基- n， o -缩醛进行的，得到具有高非对映选择性的(R)- 6,6 -二取代2-哌啶酮，手性助剂裂解后得到(-)-丁香碱。通过Lewis酸介导的环N-酰基-N， o-缩醛的烯丙化反应，成功地合成了石斛类生物碱(-)-吲哚嗪195B和209D，以及海洋生物碱(+)-星甲酰胺A和(-)-星甲酰胺b。另一方面，分子内酮羟基胺的N， o-乙酰化反应一步构建了氮杂环壬烷，然后将其转化为morphans。通过将铝试剂作为路易斯酸处理后生成的“抗bredt铝离子”与有机金属试剂形成桥头堡C-C键。由此得到的1-烷基- 1-乙烯基杂环壬烷被转化为新型免疫抑制剂FR 901483的核心环系氮杂环十二烷。酮羟基胺的N， o-乙酰化反应生成的氮杂环壬烷也被加工成海洋生物碱madang胺的二氮杂环十二烷核。
Synthesis and reaction of cyclic N,O-acetals can be of potential use and versatility in construction of polycyclic nitrogen heterocycles and alkaloid synthesis, as demonstrated in this review. The cyclic N-acyl-N,O-acetals, readily accessible by condensation of hydroxy-amines with ketocarboxylic acids, was transformed into the 2-azaspirocycles via intramolecular olefin-iminium cyclization mediated by TiCl4. Construction of the 6, 6-disubstituted 2-piperidone based on Lewis acid-mediated allylation of the cyclic N-acyl-N,O-acetals with allyltrimethylsilane led to a ladybird alkaloid adalinine in racemic form. This allylation reaction was performed with the cyclic N-acyl-N,O-acetal incorporating (R)-2-(1-aminoethyl)phenol as a chiral auxiliary to afford the (R)-6, 6-disubstituted 2-piperidone with high diastereoselectivity, which, on cleavage of the chiral auxiliary, provided (-)-adalinine. The enantioselective Lewis acid-mediated allylation of the cyclic N-acyl-N, O-acetals developed herein was successfully applied to the asymmetric syntheses of Dendrobatid alkaloids (-)-indolizidine 195B and 209D, and marine alkaloids (+) -stellettamide A and (-)-stellettamide B. On the other hand, intramolecular N ,O-acetalization of the keto-hydroxy-amines led to the one-step construction of the azabicyclononanes , which was then converted to the morphans. The azabicyclononane was subjected to bridgehead C-C bond formation with organometallic reagents via "anti-Bredt iminium ion" generated by treatment of aluminum reagents as Lewis acids. The 1-alkyland 1-vinylazabicyclononanes thus obtained were converted to the azatricyclododecane which is the core ring system of the novel immunosupressant FR 901483. The azabicyclononane formed by the N,O-acetalization of the keto-hydroxyamines was also elaborated into the diazatricyclododecane core of marine alkaloids madangamines.