Total Synthesis Of Malyngamides U, W And (±)-Palstatin

This thesis is concerned with the studies on the first and improved asymmetric total synthesis of malyngamide U, as well as malyngamide W and flavononeolignan palstatin. It mainly consists of the following three parts:First, the recent progress in research of malyngamides had been reviewed. malyngamides, a series of marine natural products, with new structures, were isolated from the metabolites of marine L. majuscule, and their good biological activity is owing to their special living environment. In this partIn chapter 2, the total synthesis of malyngamides U and W were introduced in detailed. Firstly a brief introduction of the first total synthesis of malyngamide U was given, then, an improved aymmmetric synthesis was demonstrated. In the improved route, two methods of synthesizing the long chain unsaturated fatty acids were accomplished from hexanal. The chiral centre of the 7 positon of acid portion was introduced by asymmetric allylation. The construction of the double bond was introduced by Johnson-Clainsen rearrangement and Wittig reaction, the corresponding acids were prepared in 48% and 42% overall yield, respectively. The cyclohexenone was obtained by several functional transformation of (R)-(-)-carvone in 10 steps and 24% overall yield. The chiral unsaturated acid was connected with the ethanolamine, then the resulting product was converted into aldehyde, aldol condensation of the aldehyde with the enolate of unsaturated cyclohexenone to complete the synthesis of malyngamide U and its 2'-epimer by a longest linear sequence of 13 steps in 2.7% and 0.4% overall yield, respectively. Compared to the first total synthesis of malyngamide U which was accomplished featuring with the asymmetric Henry reaction in 18 steps and 0.04 overall yield. Finally, the asymmetric synthesis of malyngamide W was investigated. PhSeSePh catalytic reductive ring opening ofα,β-epoxy ketones and fragmentation reactions ofα-alkoxy hydroperoxide was chosed as the key steps.In chapter 3, The first total synthesis of (±)-palstatin from commercially available 5-bromovanallin and 2,4,6-trihydroxyacetophenone was achieved. SeO₂ promoted oxidative cyclization reaction and Ag₂O catalyzed oxidative coupling reaction served successfully as the key steps. The synthesis was accomplished in 6 steps and 0.25% overall yield.