title: 4,4'-Bismoschamine: biomimetic synthesis and evidence to support structural equivalency to montamine.
abstract: The dimeric natural product montamine was originally reported as two N-feruloylserotonin (moschamine) units linked by a nitrogen-nitrogen bond, but our recent synthesis of this symmetrical diacyl hydrazide structure revealed this to be incorrect. We subsequently hypothesized that the moschamine subunits were linked through the indole C4 site and that montamine was structurally identical to 4,4'-bismoschamine, a known natural product present in safflower oil. However, given that authentic samples of both montamine and 4,4'-bismoschamine were unavailable and that the NMR data for the natural products were recorded in different solvents, we were unable to unequivocally prove this hypothesis. A recent publication that claims montamine and 4,4'-bismoschamine are not the same natural product prompts us to disclose our own findings on this matter. A biomimetic synthesis of 4,4'-bismoschamine was developed that hinged on oxidative coupling of N-Boc-serotonin followed by elaboration of the resulting 4,4'-dimer to the natural product. A detailed comparison of the NMR data for synthetic 4,4'-bismoschamine with that reported for montamine revealed that while the1H NMR data were in good agreement, the13C NMR data displayed some discrepancies. In light of this result, the NMR data for several literature compounds was analyzed, the results of which revealed that the upfield chemical shifts of the methylene protons in the1H NMR of montamine is unique to 4,4'-bistryptamines, supporting our initial statement that montamine and 4,4'-bismoschamine are structurally equivalent. Given that the main differences in the13C NMR data between montamine and synthetic 4,4'-bismoschamine occur at the quaternary carbons, we propose that these peaks have been misassigned from a13C NMR spectrum that was obtained from an impure sample and/or the small amount of montamine (4 mg) isolated from the natural source.
authors.affiliation: Assumption College, 500 Salisbury Street, Worcester, MA 01609, USA. ecolbydavie@assumption.edu.
authors.forename: Kaitlin G
authors.initials: KG
authors.lastname: Henry
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland, New Zealand. j.sperry@auckland.ac.nz.
authors.forename: Lachlan M
authors.initials: LM
authors.lastname: Blair
authors.affiliation: School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland, New Zealand. j.sperry@auckland.ac.nz.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sperry
authors.affiliation: Assumption College, 500 Salisbury Street, Worcester, MA 01609, USA. ecolbydavie@assumption.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Colby Davie
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D032701:Biomimetics / Q000379:methods*; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D019281:Dimerization; D007211:Indoles / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D058451:Oxidative Coupling; D012450:Safflower Oil / Q000737:chemistry; D012701:Serotonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014363:Tryptamines / Q000737:chemistry; D000438:Alcohols
chemical_list: D001688:Biological Products; D007211:Indoles; D012450:Safflower Oil; D012701:Serotonin; D014363:Tryptamines; C512561:N-feruloylserotonin; C005949:tryptophol; D000438:Alcohols; C030374:indole