Kiyooka Syun-ichi, Shahid Kazi Abdus, Goto Fumitaka, Okazaki Momotoshi, Shuto Yoshihiro
Department of Chemistry, Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan.
J Org Chem. 2003 Oct 17;68(21):7967-78. doi: 10.1021/jo034901c.
The segments C(1)-C(13) and C(15)-C(21) containing the 13 stereogenic centers required for the frame of (+)-discodermolide were synthesized in good to excellent enantio- and diastereoselectivities from a common racemic aldehyde, derived from 2-methyl-1,3-propanediol. The enantioselective aldol reactions of the racemic aldehyde with a silylketene acetal, derived from ethyl 2-bromopropionate, in the presence of chiral oxazaborolidinones, prepared in situ with N-p-toluenesulfonyl-(R)- and -(S)-valine and BH(3).THF, proceeded under kinetic control to give the stereotriads with a high degree of enantioselectivity. Enantioselective (chiral borane) and diastereoselective (BF(3).OEt(2) and TiCl(4)) aldol reactions with the silylketene acetal, coupled with diastereoselective radical debrominations (Bu(3)SnH, Et(3)B, with or without MgBr(2)), were used iteratively. This aldol reaction strategy for the construction of the polypropionate frame dramatically shortened the steps needed for the construction of the final segments.
包含（+）-盘状二萜内酯骨架所需13个手性中心的C（1）-C（13）和C（15）-C（21）片段，以良好至优异的对映选择性和非对映选择性，由源自2-甲基-1,3-丙二醇的常见外消旋醛合成。外消旋醛与由2-溴丙酸乙酯衍生的甲硅烷基烯酮缩醛在手性恶唑硼烷酮存在下进行对映选择性羟醛反应，该手性恶唑硼烷酮由N-对甲苯磺酰基-（R）-和-（S）-缬氨酸以及BH（3）·THF原位制备，在动力学控制下进行，以高对映选择性得到立体三联体。与甲硅烷基烯酮缩醛进行对映选择性（手性硼烷）和非对映选择性（BF（3）·OEt（2）和TiCl（4））羟醛反应，并结合非对映选择性自由基脱溴反应（Bu（3）SnH，Et（3）B，有或没有MgBr（2）），反复使用。这种用于构建聚丙酸酯骨架的羟醛反应策略极大地缩短了构建最终片段所需的步骤。
