Studies On The Total Synthesis Of Rocaglamide

The attempted total synthesis of natural product-Rocaglamide and its analogues was described in the dissertation. Isolated from the roots and stems of Aglaia elliptifolia (Meliace), Rocglamide has been proved to be of anti-tumor, anti-leukemic and insecticidal activities. Its structure, determined by single-crystal X-ray analysis, was reported in 1982 by King et. al. It's a challenge to synthesis of the tricyclic core structure of cyclopenta[b]benzofuran skeleton bearing a highly functionalized cyclopentane moiety with five stereogenic centers. The advantages of our short synthesis route to Rocglamide are utilizing inexpensive reagents, conducting under mild reaction conditions and obtaining the product in high stereoselectivity.First, 6-Hydroxy-2,4-Dimethoxylbenzaldehyde was prepared from anhydrous phloroglucinol via Vilsmeier-Hack reaction and dimethylation. The product reacted with 4-methoxyphenylpropan-1-one in the precence of dry HCl gas to give the flavylium salt. The benzofuran product was obtained after oxidation of the salt by H2O2. Three synthetic routes were designed based on this important intermediate.In the first route, the former structures of the target compouds were obtained by Adol and Knoevenagel reactions. The last step is synthesis of the cyclopentane ring which contains two cis adjacent aryl and phenyl substituents via Nazarov cyclization. After a great deal of attempts, we gave up this reactions. Nevertheless, we accumu -lated some experience and synthesized several new compounds.Some preliminary research has been conducted in the second route. An efficient method to synthesize of 1-(2-(4-methoxyphenyl)benzofuran-3-yl)ethanone has been discovered and the Claisen rearrangement of the intermediate has been studied. It is hopefull to complete the last three steps.In the third route, The [2+2] photocyclization is still under research. In the future research, the main task is to find a suitable solvent and light condition.