From Colchicine and Some of Its Derivatives to 1,2,3,9,10‐Pentamethoxybenzo[a]heptalenes
From Colchicine and Some of Its Derivatives to 1,2,3,9,10‐Pentamethoxybenzo[a]heptalenes
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从秋水仙碱及其一些衍生物到1,2,3,9,10-五甲氧基苯并[a]庚烯
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
H. Hansen
中科院分区：
文献类型：
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作者：
Pavlos Kouroupis;H. Hansen
已经开发了从秋水仙碱（2）开始的4-甲基秋水仙碱（13）的两步合成（方案5）。在三个步骤中，4-乙基秋水仙碱（28）也可从2获得（方案8）。秋水仙碱（2）及其衍生物13和28已分别转化为苯并[a]庚二烯衍生物9、18和34，分别通过相应的脱乙酰秋水仙碱3、19和29的霍夫曼降解，然后首先用重氮甲烷，然后用四氟硼酸三甲氧铵甲基化两个O-官能团（方案2和6）。由此形成的托吡酯盐在用Me 3 N在CHCl 3中去质子化时，分别得到预期的五甲氧基苯并[a]庚二烯9、18和34。通过对9（图3）和18（图7）的X射线晶体结构分析、H原子在庚二烯骨架上的邻位偶合常数的测定以及外消旋速率的测定，发现C（4）位取代基对庚二烯骨架的扭曲程度有显著影响。从它们的长波长CD最大值约350 nm推导出的绝对构型的解决heptalenes。在此范围内具有负最大值的庚二烯具有（7aP）-构型。
A two-step synthesis of 4-methylcolchicine (13), starting from colchicine (2), has been developed (Scheme 5). In three steps, 4-ethylcolchicine (28) is also accessible from 2 (Scheme 8). Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzo[a]heptalene derivatives 9, 18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6). The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzo[a]heptalenes 9, 18, and 34, respectively. X-Ray crystal-structure analysis of 9 (Fig.3) and 18 (Fig. 7), determination of the vicinal coupling constants of the H-atoms at the heptalene skeleton as well as the measurement of the racemization rate of the new benzo[a]heptalenes revealed a marked influence of the substituent at C(4) on the degree of twisting of the heptalene skeleton. The absolute configuration of the resolved heptalenes was deduced from their long-wavelength CD maxima around 350 nm. The heptalenes with a negative maximum in this range possess (7aP)-configuration.