Highly Stereoselective Asymmetric Total Synthesis of (−)-Jimenezin via Sequential Intramolecular Amide Enolate Alkylation

Abstract

A highly stereoselective asymmetric total synthesis of (−)-jimenezin (1), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.

Stereoselective Total Synthesis of Pyranicin and 4‐Epi‐Pyranicin from Carbohydrate Precursors

“…Subsequently, the selective iodination of the primary hydroxyl group using I 2 / Ph 3 P/imidazole under Garegg/Samuelson reaction conditions [11] provided compound 14. Benzylation of the secondary alcohol in 14 using benzyltrichloro acetimidate [12] provided 15. Zn/ EtOH [13] mediated reductive ring opening of iodo-intermediate 15 furnished the hydroxy olefin 16 in 96 % yield.…”

“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea

“…Recently, the Lee group also completed the total synthesis of (À)-jemenezin via sequential IAEA. 123 In addition to substrate-controlled alkylation reactions, the Lee group has also utilized intramolecular [3+2] cycloaddition reaction between nitrile oxide and alkene as a means to forge the macrocyclic core of various natural products. The Lee research team utilized this strategy in the total synthesis of (+)-pochonin D (380) and (+)-monocillin II, Hsp90 inhibitors with potent anticancer activity (Scheme 28b).…”

“…In the event, treatment of nitrile 375 with KHMDS yielded trans ‐substituted tetrahydrofuran derivative in 80% yield and 3.1:1 dr. 376 was moved forward to the target (+)‐chamuvarinin ( 377 ). Recently, the Lee group also completed the total synthesis of (−)‐jemenezin via sequential IAEA 123 …”