白藜芦醇二聚体Quadrangularin A和Pallidol合成方法学研究

Study on the Total Synthesis of Resveratrol Dimers Quadrangularin A and Pallidol

研究了白藜芦醇二聚体quadrangularin A (3)和pallidol (4)的全合成新方法学,设计了以廉价易得的3,5-二甲氧基苯乙腈(5)和3,5-二甲氧基苯甲醛(6)为原料,经9步反应得到天然产物quadrangularin A (3),总收率为2.6%;经11步反应得到天然产物pallidol(4),总收率为1.3%.其中,利用Knoevenagel反应在室温无需无水无氧条件下,简单高效地引入A、B两个对称或非对称芳环,拓展了二苯乙烯基多样性骨架结构中间体7,产率达98%以上,改善了文献报道中非对称结构拓展受限,产率低,操作复杂等问题.此外,通过巧妙构建4-烯醛骨架结构的关键中间体9,可高效地构筑C、D芳环,为拓展A、B、C和D芳环多样性结构的白藜芦醇类二聚体提供了新思路.所合成的中间体及天然产物结构均经~1H NMR, ^(13)C NMR, HRMS表征确证.

This paper has focused on developing a novel methodology for the total synthesis of quadrangularin A(3)and pallidol(4).These two resveratrol dimers have been obtained from the inexpensive materials of 3,5-dimethoxybenzaldehyde(5)and 3,5-dimethoxybenzaldehyde(6)within 9 steps and 11 steps with total yields of 2.6%and 1.3%,respectively.The stilbene skeleton constructed by two symmetric or asymmetric aromatic rings(A and B)has been synthesized simply through Knoevenagel reaction under mild conditions with yield of more than 98%,which expanded the diversity of stilbene skeleton(7),and addressed the problems of limited expansion of asymmetric structure,low yield and complex operation.In addition,the key intermediate of 4-enaldehyde skeleton structure(9)could be used to construct aromatic rings of C and D efficiently,which has thrown light on the expansion of resveratrol dimers with aromatic ring A,B,C and D in diversity structure.All the intermediates and natural products have been characterized by 1 H NMR,13C NMR,and HRMS.