title: Enantiospecific total synthesis of (-)-(E)16-epiaffinisine, (+)-(E)16-epinormacusine B, and (+)-dehydro-16-epiaffinisine as well as the stereocontrolled total synthesis of alkaloid G.
abstract: An efficient strategy is described for the total synthesis of the sarpagine-related indole alkaloids (-)-(E)16-epiaffinisine (1), (+)-(E)16-epinormacusine B (2), and (+)-dehydro-16-epiaffinisine (4). A key step employed the chemospecific and regiospecific hydroboration/oxidation at C(16)-C(17); this method has also resulted in the synthesis of (+)-dehydro-16-epinormacusine B (5). The oxy-anion Cope rearrangement followed by protonation of the enolate that resulted under conditions of kinetic control has been employed to generate the key asymmetric centers at C(15), C(16), and C(20) in alkaloid G (7) in a highly stereocontrolled fashion (>43:1). Conditions that favor control of the sarpagine stereochemistry at C(16) vs the epimeric ajmaline configuration at the same stereocenter have been determined. The formation of the required cyclic ether in 4, 5, and 7 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF or DDQ/aq THF in excellent yields.
authors.affiliation: Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xiangyu Z
authors.initials: XZ
authors.lastname: Wearing
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000404:Ajmaline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: C475968:(E)16-epiaffinisine; C475969:(E)16-epinormacusine B; D000470:Alkaloids; D007202:Indicators and Reagents; D026121:Indole Alkaloids; C431588:alkaloid G; C475970:dehydro-16-epiaffinisine; D000404:Ajmaline