title: Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction.
abstract: The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.
authors.affiliation: Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J M
authors.initials: JM
authors.lastname: Cook
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000470:Alkaloids; D014364:Tryptophan