Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States.
Org Lett. 2020 May 1;22(9):3537-3541. doi: 10.1021/acs.orglett.0c00972. Epub 2020 Apr 14.
Progress toward a convergent approach for the enantioselective synthesis of the alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland-Claisen rearrangement to establish the necessary relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.
呈现了一种用于手性生物碱杰尔文的对映选择性合成的收敛方法的进展。通过经济且易得的试剂，立体选择性和高效地构建了这两个必需的片段。关键反应包括：(a)高度非对映选择性的爱尔兰-Claisen 重排，以建立氨基和四氢呋喃 E 环上甲基之间的必要关系；(b)非对映选择性硒醚化反应，使 D/E 氧杂螺[4.5]癸烯以所需的构型进行组装；(c)在通往关键的四碳构建块的过程中，通过酶促去对称化大量的非手性二醇，作为 Roche 酯还原的实用替代方案。
