Synthesis of the ABC ring system of manzamine A.
A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.
Coldham
Iain
I
School of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, U.K. i.coldham@exeter.ac.uk
Crapnell
Katherine M
KM
Fernàndez
Joan-Carles
JC
Moseley
Jonathan D
JD
Rabot
Rémi
R
D001115:Arecoline / Q000737:chemistry*; D002227:Carbazoles; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D018360:Crystallography, X-Ray; D003500:Cyclization; D026121:Indole Alkaloids / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011758:Pyrroles / Q000138:chemical synthesis*; D013237:Stereoisomerism
D002227:Carbazoles; D026121:Indole Alkaloids; D007211:Indoles; D011758:Pyrroles; C078290:manzamine A; D001115:Arecoline