Total Synthesis of Spirotryprostatins through Organomediated Intramolecular Umpolung Cyclization.

Xi, Yong‐Kai; Zhang, Hongbin; Li, Rui‐Xi; Kang, Shi‐Yuan; Li, Jin; Li, Yan

Cyclodipeptide 2,5‐diketopiperazines (DKP) are privileged structural units present in drugs and natural alkaloids. This work reports a new method for the synthesis of biologically important DKP scaffolds based on an intramolecular nucleophilic α‐addition of general amides towards an alkynamide system. The utility of this umpolung cyclization mediated by trimethyl phosphine and l‐glutamic acid is highlighted by its application to the concise total syntheses of 6‐methoxyspirotryprostatin B (the first total synthesis), spirotryprostatin A, and spirotryprostatin B. Alkaloid synthesis: This work reports a concise and practical approach towards the synthesis of spirotryprostatins. This synthetic route features an organo‐mediated intramolecular umplolung cyclization to construct the DKP ring system, a Grignard addition‐dehydration‐Friedel–Crafts reaction procedure to establish the C‐ring and the prenyl moiety, and a regioselective oxidation and microwave‐assisted stereospecific rearrangement to afford the spiro‐oxindole system.

ALKALOID synthesis; INTRAMOLECULAR forces; RING formation (Chemistry); PIPERAZINE; NUCLEOPHILIC addition (Chemistry); AMIDES

Chemistry - A European Journal, 2019, Vol 25, Issue 12, p3005

0947-6539

Academic Journal

10.1002/chem.201806411