Department of Process Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Org Lett. 2011 Mar 4;13(5):1004-7. doi: 10.1021/ol1030348. Epub 2011 Feb 8.
A convergent and enantioselective route to the hNK-1 receptor antagonist (1) is described, which sets all six stereogenic centers with high diastereoselectivity and delivers 1 in only 11 steps and 23% overall yield. The process was enabled by the development of the enantioselective enzymatic reduction of 3-functionalized cyclopentenones and stereospecific Pd-catalyzed etherification coupling of fragments 6 and 7.
描述了一种具有汇聚性和对映选择性的 hNK-1 受体拮抗剂 (1) 合成路线，该路线以高非对映选择性构建了所有六个手性中心，仅通过 11 步反应以 23%的总收率得到 1。该过程得益于 3-官能化环戊烯酮的对映选择性酶还原和片段 6 和 7 的立体特异性 Pd 催化醚化偶联的发展。
