title: Synthesis of a library of complex macrodiolides employing cyclodimerization of hydroxy esters.
abstract: The synthesis of complex macrodiolides involving microwave-accelerated transesterification of chiral, nonracemic, hydroxy esters is described. Methodology development studies indicate that both microwave power and reaction temperature play an important role in the efficiency of cyclodimerizations. Hydroxy ester monomer pairs were evaluated using an analytical rehearsal leading to the preparation of a 127-member library of highly diverse and stereochemically well-defined macrodiolides. Preliminary assays identified a novel macrodiolide antagonist of the kappa opioid receptor.
authors.affiliation: Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Beeler
authors.forename: Dayle E
authors.initials: DE
authors.lastname: Acquilano
authors.forename: Qibin
authors.initials: Q
authors.lastname: Su
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: James S
authors.initials: JS
authors.lastname: Panek
authors.forename: John A
authors.initials: JA
authors.lastname: Porco
mesh_terms: D001681:Biological Assay; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D019281:Dimerization; D006880:Hydroxy Acids / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors
chemical_list: D006880:Hydroxy Acids; D018942:Macrolides; D017473:Receptors, Opioid, kappa