Asymmetric synthesis of (-)-eburnamonine and (+)-epi-eburnamonine from (4S)-4-ethyl-4-[2-(hydroxycarbonyl)ethyl]-2-butyrolactone.
The key chiral nonracemic 4,4-disubstituted 2-butyrolactone carboxylic acid, (S)-4, is readily accessible via an efficient and stereospecific dirhodium(II) tetraacetate catalyzed tertiary C-H insertion reaction of the diazomalonate (S)-5. The coupling of the acid (S)-4 with tryptamine produces the amide (S)-3, which is then transformed into the aldehyde 23 and hydroxy-lactam 24. Acid-mediated Pictet-Spengler cyclization of 23 and 24 produces the tetracyclic indole lactams (1S,12bS)-25a and (1S,12bR)-25b. Compounds 25a and 25b are converted, via the lactam alcohols 30a and 30b, to (-)-eburnamonine (1a) and (+)-epi-eburnamonine (1b).
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Department of Chemistry and Biochemistry, University of Regina, Regina, Saskatchewan, S4S 0A2, Canada. Andrew.Wee@uregina.ca
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D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry
C445790:4-4-ethyl-4-(2-(hydroxycarbonyl)ethyl)-2-butyrolactone; D007202:Indicators and Reagents; D014748:Vinca Alkaloids; C016422:eburnamonine; D015107:4-Butyrolactone