title: Jozimine A2: the first dimeric Dioncophyllaceae-type naphthylisoquinoline alkaloid, with three chiral axes and high antiplasmodial activity.
abstract: A new dimeric naphthylisoquinoline alkaloid, jozimine A(2) (2), was isolated from the root bark of an Ancistrocladus species from the Democratic Republic of Congo. Its absolute stereostructure was determined by chemical, spectroscopic, and chiroptical methods, and confirmed by X-ray crystallography. Jozimine A(2) (2) is one of the as yet very rare naphthylisoquinoline dimers whose central biaryl axis is rotationally hindered. Moreover, it is the first natural dimer of a Dioncophyllaceae-type alkaloid, that is, lacking oxygen functions at C6, and bearing R configurations at C3 in its two isoquinoline portions. Despite this decreased steric hindrance, the outer biaryl axes are chiral, too, so that jozimine A(2) (2) has three consecutive stereogenic axes and, together with the four stereogenic centers, seven elements of chirality and is C(2)-symmetric. The new dimer exhibits excellent, and specific, antiplasmodial activity. To further confirm its stereostructure and for likewise testing the bioactivities of its (unnatural) atropo-diastereomer, compound 2 was prepared by semi-synthesis from the co-occurring (and likewise synthetically available) dioncophylline A (5), along with its atropo-diastereomer, 3'-epi-2.
authors.affiliation: Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.forename: Tobias
authors.initials: T
authors.lastname: Büttner
authors.forename: Gabi
authors.initials: G
authors.lastname: Bauckmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Kupfer
authors.forename: Holger
authors.initials: H
authors.lastname: Braunschweig
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Virima
authors.initials: V
authors.lastname: Mudogo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029748:Caryophyllaceae / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000962:Antimalarials; D007546:Isoquinolines; D009281:Naphthalenes; C581448:jozimine A2