title: Aza-Quaternary Scaffolds from Selective Bond Cleavage of Bridgehead-Substituted 7-Azabicyclo[2.2.1]heptane: Total Synthesis of (+)-Cylindricines C-E and (-)-Lepadiformine A.
abstract: A novel bridgehead-substituted aza-bicyclic framework has been designed and developed in both enantiomeric forms through an asymmetric desymmetrization reaction. Strategic exploitation of the ring strain in the aza-bicyclic framework has been utilized for the construction of the chiral aza-quaterenary scaffolds by selective bond fragmentation processes. Furthermore, a strategically designed precursor is employed for selective bond cleavage to initiate a cascade rearrangement for the total synthesis of the 1-azaspirotricyclic marine alkaloids (+)-cylindricines C, D, and E, as well as (-)-lepadiformine A. An oxidation/retro-aldol/aza-Michael sequence generated three new chiral centers with the required configuration in one pot.
authors.affiliation: Molecular Synthesis and Drug Discovery Laboratory, Centre of Biomedical Research, SGPGIMS Campus, Lucknow-226014 (India). gp.pandey@cbmr.res.in.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Pandey
authors.affiliation: Molecular Synthesis and Drug Discovery Laboratory, Centre of Biomedical Research, SGPGIMS Campus, Lucknow-226014 (India).
authors.forename: Vaitla
authors.initials: V
authors.lastname: Janakiram
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C525410:7-azabicyclo(2.2.1)heptane; D000470:Alkaloids; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006575:Heterocyclic Compounds, 3-Ring; D006572:Heterocyclic Compounds, Bridged-Ring; D015363:Quinolones; C431548:lepadiformine; C485392:cylindricine D
keywords: alkaloids; asymmetric synthesis; rearrangement; spiro compounds; total synthesis