title: Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua.
abstract: The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an α,α-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported (13)C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 μM) of 6 was 40 times stronger than that of arbutin (174 μM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds.
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Youta
authors.initials: Y
authors.lastname: Sugano
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Shirato
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sonoda
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Tsutsui
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ninomiya
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: †Faculty of Pharmacy and ‡Pharmaceutical Research and Technology Institute, Kinki University, Higashi-osaka, Osaka 577-8502, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001104:Arbutin / Q000494:pharmacology; D001938:Brazil; D004952:Esters; D008543:Melanins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: C000602204:4,5-didehydroguadiscine; D001060:Aporphines; D004952:Esters; D008543:Melanins; D001104:Arbutin