Part I: Study on the total synthesis of natural product (-)-englerin A.
The natural product (-)-Englerin A( 1) is a guaiacane-type sesquiterpene compound extracted from Phyllanthus urinaria of Euphorbiaceae, which has high inhibitory activity and selectivity on renal cell carcinoma. The basic skeleton of (-)-Englerin A is trans -5-7 with seven chiral centers. Because of its special structure and remarkable anticancer activity, it has attracted extensive attention of organic synthetic chemists all over the world. This paper has completed a brand-new and efficient (-)-English synthesis route. Based on the closed-loop reaction of olefin metathesis and the construction of high stereoselectivity oxygen bridge tricyclic skeleton induced by iodine ions, this route completed the total synthesis of three natural products (-)-Engelin A( 1), (-)-Engelin B(2) and (-)-Engelin acetate (3). In addition, the oxygen bridging strategy induced by iodine ion laid a good foundation for the synthesis and structure-activity relationship study of 9- substituted EnglerinA derivatives.
Part II: Methodological study on the synthesis of polyalkyl substituted benzene by platinum-catalyzed RCM aromatization.
Polyalkyl substituted benzene is an important part of organic chemistry, natural medicinal chemistry and material chemistry. Traditionally, the synthesis of polysubstituted benzene is usually realized by Foucault reaction or [2+2+2] or [4+2] cycloaddition catalyzed by transition metals. However, in the regioselective synthesis of polysubstituted benzene (with more than 4 substituents), the application of these two strategies has certain limitations. In this paper, platinum (IV) catalyzed synthesis of polyalkyl-substituted benzene from 1, 7- enyne by metathesis closed-loop reaction (RCM) and aromatization "one-pot synthesis" was found. This reaction is a series reaction of metathesis closed-loop reaction (RCM), dehydration reaction and double bond isomerization reaction, which has regional specificity. The method is simple and efficient, the substrate is easily available, the yield is high, and it has wide applicability. Synthetic polyalkyl substituted benzene includes highly substituted benzene derivatives, such as tri-substitution, tetra-substitution, pentasubstitution and hexasubstitution. By this method, we completed the total synthesis of 1- ethyl -2- propyl -3- butyl -4- pentyl -5- hexyltoluene with a high yield of 78%. At the same time, a natural product, AlcyopterosinA(247), was completely synthesized.