Synthesis of a library of complex macrodiolides employing cyclodimerization of hydroxy esters.
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.
Beeler
Aaron B
AB
Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA.
Acquilano
Dayle E
DE
Su
Qibin
Q
Yan
Feng
F
Roth
Bryan L
BL
Panek
James S
JS
Porco
John A
JA
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
D006880:Hydroxy Acids; D018942:Macrolides; D017473:Receptors, Opioid, kappa