New approaches for the synthesis of erythrinan alkaloids.
A concise asymmetric total synthesis of (+)-erysotramidine is described, using chiral base desymmetrisation of a meso-imide, N-acyliminium addition, retro-Diels-Alder cycloaddition and radical cyclisation as the key steps. A related route, starting from a cyclobutene-fused imide, was explored, and established a novel construction of the Erythrina alkaloid skeleton using a key ring-opening/ring-closing metathesis step. Completion of this synthesis was thwarted by problems with the removal of an unwanted vinylic side-chain. Complementary enantiospecific routes to Erythrina systems were explored, starting from (L)-malic acid. Some unexpected observations were made concerning the diastereocontrol in malic acid-derived N-acyliminium ion cyclisations, where changing the protecting group of the alcohol function from acetate to OTIPS resulted in a dramatic change in diastereocontrol. Products from these reactions could be transformed into known intermediates for natural alkaloids, and into (+)-demethoxyerythratidinone itself, by means of radical cyclisations or intramolecular aldol reactions as the key steps.
Zhang
Fengzhi
F
The School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, U.K.
Simpkins
Nigel S
NS
Blake
Alexander J
AJ
D000470:Alkaloids / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D003500:Cyclization; D004895:Erythrina / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D007097:Imines / Q000737:chemistry; D008293:Malates / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000470:Alkaloids; D005609:Free Radicals; D006576:Heterocyclic Compounds, 4 or More Rings; D007097:Imines; D008293:Malates; C492626:erysotramidine; C030298:malic acid