title: Unraveling the bastarane and isobastarane oximo amide configurations and associated macrocycle conformations: implications of their influence on bioactivities.
abstract: Our rigorous re-examination of the conformational properties of bastadins that comprise the isobastarane and bastarane-type macrocycle has generated some interesting new insights. We determined that these macrocycles are flexible and possess a surprising degree of reflection symmetry that generates enantiomeric conformations. The macrocycle symmetry arises from its ability to twist in a disrotatory fashion, providing one set of conformers, and then twists with the opposite disrotation to generate a corresponding set of enantiomers. Overall, the isobastarane conformations for (E,E)-bastadin 19 (1a) are complex and can access several distinct ring conformations. In contrast, the bastarane macrocycle in bastadin 5 (2) and bastadin 6 (3) maintains a similar overall shape. We postulate that the short-term stability of the (Z)-oximo amide, an uncommon configuration found in bastadins and psammaplins, is due to the existence of conformers with intramolecular hydrogen bonds involving the (Z)-oxime, and hydrogen bonding impedes oxime isomerization to the more stable (E)-oximo amide in solution. Finally, the modeling results provided insights toward understanding the different antiproliferative activity against endothelial cells as well as Ca(2+) channel modulation activities attributed to bastaranes 2 and 3 versus isobastarane 1a.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States. winman@ucsc.edu
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Inman
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D000577:Amides / Q000737:chemistry; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000577:Amides; D055768:Halogenated Diphenyl Ethers; D010091:Oximes; D010456:Peptides, Cyclic; C558351:bastadin 19; C515158:bastadin 6; C105188:bastadin 5