Application of cross-conjugated heteroaromatic betaines to the synthesis of the schizozygane alkaloid (+/-)-strempeliopine.
An efficient stereocontrolled route to the isoschizozygane alkaloid core has been developed utilizing an intramolecular 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes loss of COS, and further reduction delivers a 5a-azaacenaphthylene intermediate that was transformed into the isoschizozygane skeleton upon treatment with acid. A variation of this tactic was then employed for a synthesis of the hexacyclic framework of the shizozygane alkaloid (+/-)-strempeliopine. The key step of the synthesis corresponds to an intramolecular 1,4-dipolar cycloaddition of a heteroaromatic betaine across a tethered 4-((2-nitrophenyl)but-3-enyl) side chain. Catalytic reduction of the nitro group followed by reaction with NBS resulted in the formation of the required pentacyclic indoline framework of the target alkaloid. Closure of the final ring of the shizozygane skeleton was carried using an oxidative cyclization.
Bobeck
Drew R
DR
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Lee
Hyoung Ik
HI
Flick
Andrew C
AC
Padwa
Albert
A
D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry*; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D026121:Indole Alkaloids; C519431:schizozygane; C545379:strempeliopine; D001622:Betaine