Applications of vinylogous Mannich reactions. Total syntheses of the Ergot alkaloids rugulovasines A and B and setoclavine.
Concise syntheses of the Ergot alkaloids rugulovasine A (3a), rugulovasine B (3b), and setoclavine (2) have been completed by strategies that feature inter- and intramolecular vinylogous Mannich reactions as the key steps. Thus, the first synthesis of 3a,b commenced with the conversion of the known indole 17 into 24 via the addition of the furan 22 to the iminium ion 21, which was generated in situ from the aldehyde 19. Cyclization of 24 by a novel S(RN)1 reaction followed by removal of the N-benzyl group furnished a mixture (1:2) of 3a and 3b. In an alternative approach to these alkaloids, the biaryl 35 was reduced with DIBAL-H to give an intermediate imine that underwent spontaneous cyclization via an intramolecular vinylogous Mannich addition to provide 36a,b. N-Methylation of the derived benzyl carbamates 37a,b followed by global deprotection gave a mixture (2:1) of rugulovasines A and B (3a,b). Setoclavine (2) was then prepared from the biaryl 41 using a closely related intramolecular vinylogous Mannich reaction to furnish the spirocyclic lactones 42a,b. These lactones were subsequently transformed by hydride reduction and reductive methylation into the ergoline derivatives 43a,b, which were in turn converted into 2 by deprotection and solvolytic 1,3-rearrangement of the allylic hydroxyl group.
Liras
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Department of Chemistry and Biochemistry, The University of Texas, Austin, TX 78712, USA.
Lynch
C L
CL
Fryer
A M
AM
Vu
B T
BT
Martin
S F
SF
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D004876:Ergot Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009183:Mycotoxins / Q000138:chemical synthesis / Q000737:chemistry
D000470:Alkaloids; D004876:Ergot Alkaloids; D007202:Indicators and Reagents; D007211:Indoles; D009183:Mycotoxins; C027115:rugulovasine B; C027114:rugulovasine A; C434067:setoclavine