SEARCHING CONFORMATIONAL SPACE IN FLEXIBLE MOLECULES USING NOES AND MOLECULAR MODELING

A routine method for searching the conformational space of small flexi ble chain molecules in solution is presented. This involves the quanti tative use of NOEs aided by molecular modeling. The l diastereomer of model compound -(1-phenylethyl)-2-(ethylsulfinyl)-1-propenylamine (1) was studied in CDCl3 and pyridine-d(5) solutions using H-1 NMR. It was shown to undergo self-association in CDCl3. Comparison of calculated and observed steady-state NOE values and the kinetics of NOEs shows th at the compound has the E geometry around the double bond. The conform ational space accessible to the sulfinyl enamine was searched using th e program PCMODEL with the help of ancillary programs and programs to calculate theoretical NOEs. These conformations could be limited subst antially by using coupling constants and by comparing observed NOEs to those calculated by assuming conformational averaging about a small n umber of energy minima.