Denmark Scott E, Kobayashi Tetsuya, Regens Christopher S
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801.
Tetrahedron. 2010 Jun 26;66(26):4745-4759. doi: 10.1016/j.tet.2010.03.093.
A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron rich and sterically hindered aromatic iodide and (2) a Lewis base-catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.
已通过31步反应实现了（+）-papulacandin D的全合成，以市售原料计总收率为9.2%。合成策略将该分子分为两个大小几乎相等的亚基，即螺环C-芳基葡萄糖苷和多不饱和脂肪酸侧链。C-芳基葡萄糖苷由三乙酰氧基葡糖醛通过11步反应制备，总收率为30%。脂肪酸侧链也由香叶醇通过11步反应制备，总收率为30%。合成中的关键策略转变包括：（1）钯催化的、基于有机硅醇盐的二甲基葡糖醛-硅醇与富电子且空间位阻较大的芳基碘的交叉偶联反应，以及（2）路易斯碱催化的二烯醛与烯丙基三氯硅烷的对映选择性烯丙基化反应。成功完成该合成的一个关键因素是开发出一种满足多项严格标准的合适保护基策略。
