Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Prod Rep. 2020 Nov 18;37(11):1478-1496. doi: 10.1039/d0np00028k.
Covering: 2000 to 2020 The hallucinogenic diterpene salvinorin A potently and selectively agonizes the human kappa-opioid receptor (KOR). Its unique attributes-lack of a basic nitrogen, rapid brain penetrance, short half-life-combined with the potential of KOR as an emerging target for analgesics have stimulated extensive medicinal chemistry based on semi-synthesis from extracts of Salvia divinorum. Total synthesis efforts have delivered multiple, orthogonal routes to salvinorin A, its congeners and related analogs with the goal of optimizing its activity towards multiple functional endpoints. Here we review total syntheses of the salvinorin chemotype and discuss outstanding problems that synthesis can address in the future.
2000 年至 2020 年 致幻二萜化合物 salvinorin A 强效且选择性地激动人类 κ-阿片受体（KOR）。其独特属性——缺乏碱性氮原子、快速穿透大脑、半衰期短——再加上 KOR 作为新兴的镇痛药靶点的潜力，刺激了基于 Salvia divinorum 提取物的半合成的广泛药物化学研究。全合成工作已经提供了多种、正交的路线来合成 salvinorin A、其同系物和相关类似物，目的是优化其对多个功能终点的活性。本文我们综述了 salvinorin 类化合物的全合成，并讨论了合成在未来可以解决的突出问题。
