title: Structural Determination of (-)-SCH 64874 and Hirsutellomycin by Semisynthesis.
abstract: The structure of a C2-symmetric epidithiodiketopiperazine alkaloid, SCH 64874, was determined by semisynthesis. The relative stereochemistry of the β-hydroxy carboxylic acid chain having three chiral centers was determined by comparison of the NMR data of the four possible diastereomeric β-hydroxy carboxylic acid fragments with those of SCH 64874. Condensation of the (-)-deacetylaranotin core with two enantiomeric β-hydroxy carboxylic acids revealed the relative stereochemistry of SCH 64874. The relative stereochemistry of the β-keto carboxylic acid chain of the analogous alkaloid hirsutellomycin was determined in a stepwise manner. The C4'-C6' syn relationships were predicted by comparing the NMR data of the corresponding ester fragments with that of hirsutellomycin. The relative stereochemistry of the whole molecule, including the epimerizable C2' stereocenter, was determined by introduction of four possible side chains into the bisdethiodi(methylthio)deacetylaranotin core. We found that the stereochemistry of C2' converged with that of the thermodynamically stable form influenced by the core structure.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Hidetoshi
authors.identifier: 0000-0002-6519-7727
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Sakata
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University , Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okano
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC) , 113 Thailand Science Park, Phaholyothin Road, Klong Luang, Pathumthani 12120, Thailand.
authors.forename: Malipan
authors.initials: M
authors.lastname: Sappan
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC) , 113 Thailand Science Park, Phaholyothin Road, Klong Luang, Pathumthani 12120, Thailand.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Isaka
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D002264:Carboxylic Acids; D054659:Diketopiperazines; D010879:Piperazines; C000627294:SCH 64874; D000077489:Piperazine