title: Stereospecific approach to the synthesis of ring-A oxygenated sarpagine indole alkaloids. Total synthesis of the dimeric indole alkaloid P-(+)-dispegatrine and six other monomeric indole alkaloids.
abstract: The first regio- and stereocontrolled total synthesis of the bisphenolic, bisquaternary alkaloid (+)-dispegatrine (1) has been accomplished in an overall yield of 8.3% (12 reaction vessels) from 5-methoxy-d-tryptophan ethyl ester (17). A crucial late-stage thallium(III) mediated intermolecular oxidative dehydrodimerization was employed in the formation of the C9-C9' biaryl axis in 1. The complete stereocontrol observed in this key biaryl coupling step is due to the asymmetric induction by the natural sarpagine configuration of the monomer lochnerine (6) and was confirmed by both the Suzuki and the oxidative dehydrodimerization model studies on the tetrahydro β-carboline (35). The axial chirality of the lochnerine dimer (40) and in turn dispegatrine (1) was established by X-ray crystallography and was determined to be P(S). Additionally, the first total synthesis of the monomeric indole alkaloids (+)-spegatrine (2), (+)-10-methoxyvellosimine (5), (+)-lochnerine (6), lochvinerine (7), (+)-sarpagine (8), and (+)-lochneram (11) were also achieved via the common pentacyclic intermediate 16.
authors.affiliation: Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, USA.
authors.forename: Chitra R
authors.initials: CR
authors.lastname: Edwankar
authors.forename: Rahul V
authors.initials: RV
authors.lastname: Edwankar
authors.forename: Ojas A
authors.initials: OA
authors.lastname: Namjoshi
authors.forename: Xuebin
authors.initials: X
authors.lastname: Liao
authors.forename: James M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D026121:Indole Alkaloids; C049053:dispegatrine; D010100:Oxygen