A versatile approach for the asymmetric syntheses of (1R,9aR)-epiquinamide and (1R,9aR)-homopumiliotoxin 223G.
[reaction: see text] Using 5b as a common intermediate, the first asymmetric synthesis of (-)-epiquinamide (4) and a formal asymmetric synthesis of (-)-homopumiliotoxin 223G (2) is described. A key feature of our approach is the flexible introduction of a functionalized C(4) side chain to (S)-3-benzyloxyglutarimide 7 in a regio- and diastereoselective manner. Utilization of a tandem Swern oxidation-Grignard addition strategy efficiently prevented racemization. An unexpected NaN(3)-promoted methanesulfonic acid elimination yielded 17, a reaction which could be useful for the syntheses of 8-dehydrodesmethylpumiliotoxins such as alkaloid 235C (3).
Huang
Pei-Qiang
PQ
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.
Guo
Zheng-Qing
ZQ
Ruan
Yuan-Ping
YP
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D010881:Piperidones / Q000737:chemistry*; D011807:Quinolizines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D007212:Indolizines; D010880:Piperidines; D010881:Piperidones; D011807:Quinolizines; C506977:alkaloid 235C; C481035:epiquinamide; C414694:homopumiliotoxin 223G; C007864:glutarimide