title: Synthesis of 2,3- and 3,4-methanoamino acid equivalents with stereochemical diversity and their conversion into the tripeptide proteasome inhibitor belactosin a and its highly potent cis-cyclopropane stereoisomer.
abstract: A series of chiral 2,3- and 3,4-methanoamino acid equivalents of stereochemical diversity were designed and synthesized from our chiral cyclopropane units, using a diastereoselective Grignard addition with ( R)- or ( S)- t-butanesulfinyl imines as the key step. These equivalents were converted into the proteasome inhibitor belactosin A and its cis-cyclopropane stereoisomer. The unnatural cis-isomer was shown to be more than twice as potent as belactosin A as a proteasome inhibitor.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sone
authors.forename: Yuka
authors.initials: Y
authors.lastname: Unno
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Yokosawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Arisawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D003521:Cyclopropanes; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011480:Protease Inhibitors; C406052:belactosin A