Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
Org Lett. 2020 Nov 6;22(21):8496-8499. doi: 10.1021/acs.orglett.0c03096. Epub 2020 Oct 15.
The first enantio- and diastereoselective synthesis of Tepe's human proteasome modulator is described. Routes to this and other highly substituted chiral imidazolines generally produce racemic material. Key to the route disclosed here is a gram-scale -selective aza-Henry reaction of an α-alkyl α-nitro ester nucleophile, catalyzed by a Bis(Amidine) [BAM] chiral proton complex, delivering the key intermediate in high yield as a single stereoisomer. The adduct is reduced to the amino ester and converted to an imidazoline.
本文描述了 Tepe 的人蛋白酶体调节剂的首次对映选择性和非对映选择性合成。通常，合成这些和其他高度取代的手性咪唑啉的路线会产生外消旋体材料。此处公开的路线的关键是通过双（脒基）[BAM]手性质子配合物催化的α-烷基α-硝基酯亲核试剂的克级选择性氮杂 Henry 反应，以高收率作为单一立体异构体提供关键中间体。将加成物还原为氨基酯，并将其转化为咪唑啉。
