title: Synthesis, structure determination, and biological evaluation of destruxin E.
abstract: The total synthesis of destruxin E (1) has been achieved for the first time, and the stereochemistry of its chiral center at the epoxide has been determined to be (S). The cyclization precursor 3a was synthesized by solid-phase peptide synthesis. Macrolactonization of 3a utilizing MNBA-DMAPO, followed by formation of the epoxide, then furnished destruxin E. Its diastereomer, epi-destruxin E (2), was also synthesized in the same manner. Furthermore, the biological evaluation indicated that destruxin E exhibits V-ATPase inhibitory activity 10-fold greater than that of epi-destruxin E.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ishida
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yashiroda
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Motoki
authors.initials: M
authors.lastname: Takagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-ya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
mesh_terms: D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005656:Fungal Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
chemical_list: D047630:Depsipeptides; D005656:Fungal Proteins; D025262:Vacuolar Proton-Translocating ATPases; C040425:destruxin E