A protecting group free synthesis of (+/-)-neostenine via the [5 + 2] photocycloaddition of maleimides.
A concise, linear synthesis of the Stemona alkaloid (+/-)-neostenine is reported. Key features include an organocopper-mediated bislactone C2-desymmetrization for the stereoselective construction of the cyclohexane-lactone C,D-rings. The assembly of the fused pyrrolo[1,2-a]azepine core was achieved by application of a [5 + 2] maleimide photocycloaddition. A custom FEP flow reactor was used to successfully overcome the scale limitations imposed by a classical immersion well batch reactor. The synthesis was completed in 14 steps from furan, in 9.5% overall yield, without the use of any protecting groups.
Lainchbury
Michael D
MD
School of Chemistry, Cantock's Close, University of Bristol, Bristol BS8 1TS, UK.
Medley
Marcus I
MI
Taylor
Piers M
PM
Hirst
Paul
P
Dohle
Wolfgang
W
Booker-Milburn
Kevin I
KI
D000470:Alkaloids / Q000138:chemical synthesis*; D001381:Azepines / Q000737:chemistry; D003510:Cyclohexanes / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry*; D008956:Models, Chemical; D010777:Photochemistry; D011758:Pyrroles / Q000737:chemistry; D041901:Stemonaceae / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D001381:Azepines; D003510:Cyclohexanes; D005663:Furans; D007783:Lactones; D008301:Maleimides; D011758:Pyrroles; C441784:stenine; C043592:maleimide; C506365:Cyclohexane