| As a family of natural products with the structure of 1,7-dioxadispiro[5.1.5.2] pentadecane, the Aculeatins were first isolated in 2000, whose significant antiproton-zoal activity made it had an important position in the field of research and the develo-pment of antimalarial drugs.Since 2002, after Wong and his colleagues’ construction of 1,7-dioxadispiro [5.1.5.2]pentadecane structure by one-step oxidative cyclization tandem reaction, there have been many reports on the total synthesis of Aculeatins were published. In the above background, we designed a new synthetic route to product Aculeatins. We used classical asymmetric Mukaiyama Aldol reaction to build the first chiral hydroxyl which was included in Aculeatin’ cyclization precursor with high selectivity and high yield. Then the carbonyl of the first chiral hydroxyl group’s β-position was selective reducted under the induction of the first chiral hydroxyl group through the use of suitable boron reagents and the successful construction of second chiral hydroxyl group was accomplished. Thus, the construction of the two essential chiral centers included in Aculeatin’ cyclization precursor was complished. Sequentially, the above main structure was modified into Weinrebamide structure, then, introducted the triple bond structure through one step alkylation. In the end, one step oxidative cyclization tandem reaction was initiated through using PIFA and the 1, 7-dioxadispiro[5.1.5.2]pentadecane structure was constructed. The whole process experienced eight steps and the total synthesis of Aculeatins D,6-epi-D can be completed in the same line.In total, our synthetic strategy was simple, feasible, effective, which was suitable to the synthesis of many Aculeatins. The strategy, which utilized asymmetric Mukaiyama Aldol reaction to construct chiral hydroxyl which could induce the selective reduction of the carbonyl at β-position, could be used in the total synthesis of other natural products as a valuable experience. |
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