title: Total synthesis of (+)-antofine and (-)-cryptopleurine.
abstract: The tylophorine alkaloid anticancer compounds antofine and cryptopleurine have been synthesized in optically active form. Both syntheses employ optically pure α-amino acids as the starting materials, require only seven steps from known 2-ethynylpyrrolidine or 2-ethynylpiperidine derivatives, and are free of protecting groups. Key steps include an alkyne hydration and a chromium carbene complex based net [5+5]-cycloaddition step. Alkyne hydration was accompanied by racemization of the resulting β-aminoketone under most of the conditions examined, and successful minimization of this side reaction was achieved through careful pH control and choice of metal additive. Final ring closure involves a Bischler-Napieralski reaction using a carbamate (antofine) or urea (cryptopleurine) precursor.
authors.affiliation: Department of Chemistry and Biochemistry, New Mexico State University, MSC 3C, Las Cruces, NM 88003 USA.
authors.forename: Weijiang
authors.initials: W
authors.lastname: Ying
authors.affiliation: Department of Chemistry and Biochemistry, New Mexico State University, MSC 3C, Las Cruces, NM 88003 USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Herndon
keywords: Alkynes; Carbene Ligands; Chromium; Cycloaddition; Hydration; Racemization