An expedient route to Montanine-type Amaryllidaceae alkaloids: total syntheses of (-)-brunsvigine and (-)-manthine.
The first total syntheses of (-)-brunsvigine (1) and (-)-manthine (2) were accomplished in 10 and 18 steps, respectively. (-)-Quinic acid was converted to enone 12 in five steps. Iodination of enone 12 followed by stereoselective reduction yielded alpha-iodo allylic alcohol 16. Conversion of alcohol 16 into Weinreb amide 11 followed by anionic cyclization gave bicyclic enone 10. Stereoselective reduction of enone 10 and subsequent protection afforded pivaloate 9. Grignard addition of 8 to 9 and detosylation afforded amine derivative 19. Pictet-Spengler cyclization of 19 with Eschenmoser's salt and subsequent hydrolysis gave enantiomerically pure (-)-brunsvigine (1). For the total synthesis of (-)-manthine (2), the key intermediate 7 was hydrolyzed to diol 21. Conversion of 21 into 22 followed by regioselective cleavage with DIBAL furnished alcohol 25. Alcohol 25 was converted to the corresponding triflate 26, which on treatment with CsOAc and 18-crown-6 gave stereoinverted acetate 27. Hydrolysis of acetate 27 followed by methylation afforded compound 29. Detosylation of 29 afforded amine derivative 30. Pictet-Spengler cyclization of 30 followed by debenzylation gave alcohol 33. Finally, methylation of alcohol 33 afforded (-)-manthine (2).
Hong
An-Wei
AW
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
Cheng
Tsung-Hui
TH
Raghukumar
Vellingiri
V
Sha
Chin-Kang
CK
D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis*; D007546:Isoquinolines; D011801:Quinic Acid / Q000737:chemistry; D013237:Stereoisomerism
D047151:Amaryllidaceae Alkaloids; D007546:Isoquinolines; C432323:brunsvigine; C533113:manthine; C517208:montanine; D011801:Quinic Acid