title: Conformationally restricted analog and biotin-labeled probe based on beauveriolide III.
abstract: A conformationally restricted oxazoline analog 7 was designed on the basis of a SAR study of beauveriolide III (2) and its analogs reported previously. Conformational analysis by molecular mechanics calculation suggested that the three side chains of 7 mostly occupy the same spaces as those of 2. The analog 7 was synthesized by peptide coupling of the d-cyclohexylglycine-containing ester 11 and d-Ser-containing dipeptide 12, macrolactamization, and cyclodehydration of 6 for the construction of an oxazoline ring. The bicyclic 7 exhibited potential inhibitory activity for cholesteryl ester synthesis similar to that by 2. These results revealed biologically important 3D spaces of the three side chains in inhibitory activity for cholesteryl ester synthesis. In addition, we accomplished the synthesis of a biotin-labeled probe 8 by copper-catalyzed (3+2) cycloaddition of a biotin-containing alkyne 16 and azido-containing beauveriolide analog 15 prepared from 6.
authors.affiliation: Tohoku University, Graduate School of Pharmaceutical Sciences, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. doi_taka@mail.pharm.tohoku.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
authors.forename: Terushige
authors.initials: T
authors.lastname: Muraoka
authors.forename: Taichi
authors.initials: T
authors.lastname: Ohshiro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.forename: Masahito
authors.initials: M
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002788:Cholesterol Esters / Q000737:chemistry; D047630:Depsipeptides / Q000737:chemistry*; D015195:Drug Design; D004952:Esters / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015335:Molecular Probes / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D002788:Cholesterol Esters; D047630:Depsipeptides; D004952:Esters; D015335:Molecular Probes; D010455:Peptides; C013833:beauverolides; D001710:Biotin