Smith Amos B, Jurica Jon A, Walsh Shawn P
Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Org Lett. 2008 Dec 18;10(24):5625-8. doi: 10.1021/ol802466t.
An effective total synthesis of the marine sponge cytotoxin (+)-psymberin [irciniastatin A (1)] has been achieved. Highlights of the strategy include a Diels-Alder reaction between a bis-siloxy diene and an allene to construct the aromatic ring, a boron-mediated aldol reaction to elaborate the C(15-17) all syn stereotriad, catalytic reagent control to set the C(8, 9, 11 and 13) stereogenic centers of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the sensitive N,O-aminal moiety. The synthesis proceeds with a longest linear sequence of 21 steps from commercially available 2,2-dimethyl-1,3-propanediol.
已实现海洋海绵细胞毒素（+）-psymberin [刺参他汀A（1）]的有效全合成。该策略的亮点包括双硅氧基二烯与丙二烯之间的狄尔斯-阿尔德反应以构建芳环、硼介导的羟醛反应以构建C（15-17）全顺式立体三联体、催化试剂控制以确定四氢吡喃核心的C（8、9、11和13）立体中心，以及后期的库尔提斯重排以安装敏感的N，O-氨基部分。该合成从市售的2,2-二甲基-1,3-丙二醇开始，最长线性序列为21步。
