Synthetic furocoumarins. IX. New synthetic route to psoralen
Synthetic furocoumarins. IX. New synthetic route to psoralen
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合成呋喃香豆素。
DOI：
10.1021/jo01260a015
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发表时间：
1969
影响因子：
3.6
通讯作者：
T. Schaaf
中科院分区：
文献类型：
--
作者：
L. R. Worden;K. D. Kaufman;J. A. Weis;T. Schaaf
Practical syntheses of psoralen (IVb) and 3-methylpsoralen (IVc) fromß-resorcylaldehyde are described. Bromination of ethyl (2-formyl-5-methoxyphenoxy) acetate gave the 4-bromoderivative la, which was saponified and simultaneously cyclized and decarboxylated to 5-bromo-6-methoxybenzofuran (Ha). Lithium-bromine in-terchange and then formylation and demethylation gave 5-formyl-6-hydroxybenzofuran (III), which was con-densed with diethyl malonate to furnish psoralen after hydrolysis and decarboxylation of the Knoevenagel product IVa. Condensation of III with propionic anhydride furnished 3-methylpsoralen (IVc) directly.Unfavorable directive effects associated with syn-theses of psoralens unsubstitutedin the 9 position have limited yields of the naturally occurring phototoxin psoralen (IVb, Scheme I) to 1-4% over-all from re-sorcinol or/3-resorcylaIdehyde. 3 However, Chatterjee and Sen recently reported a 15% conversionof re-sorcinol into psoralen. 4 5Although their scheme now is the route of choice to psoralen itself, the synthesis lacks the versatility of the novel Scheme I, which represents a 14% conversion of/3-resorcylaldehyde into psoralen. Ethyl (4-bromo-2-formyl-5-methoxyphenoxy) acetate (la) was prepared both by bromination ofethyl (2-formyl-5-methoxyphenoxy) acetate6 and byalkylation of 5-bromo-2-hydroxy-p-anisaldehyde. 6 Saponification of the ester la and then decarboxylative cyclization in ace-tic acid-acetic anhydride7gave the bromobenzofuran Ha and a trace quantity of a carboxylic acid identified
