An unusual intramolecular hetero-Diels-Alder cycloaddition.
A new reaction of erythronolides, an intramolecular hetero-Diels-Alder, has been discovered. Heated aqueous alcoholic solutions of ABT-773 (1) and its cis isomer (3) convert slowly to cycloadducts 2 and 4, respectively. Optimal reaction conditions, mechanistic studies supported by molecular modeling, and biological activity data are reported. Single-crystal X-ray structures for both adducts 2 and 4 have been obtained.
Stoner
Eric J
EJ
Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 60064-6290, USA. eric.stoner@abbott.com
Allen
Michael S
MS
Christesen
Alan C
AC
Henry
Rodger F
RF
Hollis
L Steven
LS
Keyes
Robert
R
Marsden
Ian
I
Rehm
Tamara C
TC
Shiroor
Sandeep G
SG
Soni
Niru B
NB
Stewart
Kent D
KD
D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048628:Ketolides / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
D048628:Ketolides; D004917:Erythromycin; C405499:cethromycin