title: Synthesis, absolute configuration, and enantiomeric enrichment of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin, and its oxazoline analog.
abstract: Stereochemical studies of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin [(-)-4], and its oxazoline analogue, spirooxazoline (11), were carried out. Racemic spirobrassinin [(+/-)-4] was synthesized by SOCl(2)- or MsCl-mediated cyclization of dioxibrassinin [(+/-)-8]. Treatment of (3-hydroxyoxindol-3-yl)methylammonium chloride [(+/-)-9] with CSCl(2) and subsequent methylation of the obtained spirooxazolidinethione (+/-)-10 afforded spirooxazoline [(+/-)-11]. Enantioresolution of (+/-)-4 and (+/-)-11 was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate (12), chromatographic separation of diastereomeric amides 13, 14 or 15, 16, and their cleavage with CH(3)ONa. Absolute configuration of the stereogenic center in natural (S)-(-)-4 was derived from the exciton, calculated via CD methods, and unequivocally confirmed by X-ray crystallographic analyses of 1-[1'S,4'R-(-)-camphanoyl] derivatives [(-)-19 and (-)-20] of (+)- and (-)-4. Novel enantiomeric enrichment phenomena of 4 and 11 were discovered during their chromatographic separations under achiral HPLC conditions. Screening of antifungal activity against the fungus Bipolaris leersiae revealed no significant dependence of this activity on absolute configuration.
authors.affiliation: Department of Organic Chemistry, P. J. Safárik University, Moyzesova 11, 041 67 Kosice, Slovak Republic.
authors.forename: M
authors.initials: M
authors.lastname: Suchý
authors.forename: P
authors.initials: P
authors.lastname: Kutschy
authors.forename: K
authors.initials: K
authors.lastname: Monde
authors.forename: H
authors.initials: H
authors.lastname: Goto
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Takasugi
authors.forename: M
authors.initials: M
authors.lastname: Dzurilla
authors.forename: E
authors.initials: E
authors.lastname: Balentová
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001203:Ascomycota / Q000187:drug effects; D019607:Brassicaceae / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D010080:Oxazoles; D013141:Spiro Compounds; D013844:Thiazoles; C417935:spirobrassinin