A slow rate exchange process allows the detection of both carbonyl (CO) and hydroxyl (OH) 17O nuclear magnetic resonances of the carboxylic group

In this study we report, for the first time, on the detection of both the carbonyl (CO) and the hydroxyl (OH) 17O resonances of the carboxylic group by 17O NMR spectroscopy. Two well separated peaks, at 340.3 and 175 ppm, were detected for the CO and OH groups, respectively, of Boc-[17O]Tyr(2,6-diClBzl)-OH in DMSO-d6. This finding is attributed to the participation of the carboxylic group in a rather strong hydrogen-bonded interaction. These resonances disappeared in the presence of a small quantity of TFA (trifluoroacetic acid), which, however, did not cleave the Boc-group and a broad resonance was detected for both oxygens. In fact, this result indicates that the proposed hydrogen-bonded interaction is not stabilized in the presence of TFA, which is a very strong hydrogen bond breaker. Only one broad signal was observed for both carboxylic oxygens at 251.8 ppm for the HCl[17O]Tyr(2,6-diClBzl)-OH in DMSO-d6 solution, suggesting that the carbonyl oxygen of the Boc-group is probably the proton acceptor group of the carboxylic hydrogen, stabilizing a γ-turn like structure. A single relatively sharp resonance appearing in chloroform, (247.5 ppm) upfield shifted by ∼14.5 ppm, compared to the resonance found in DMSO-d6 for Boc-[17O]Tyr(2,6-ClBzl)-OH in the presence of TFA, is attributed to a γ-turn fraction being in a fast exchange with the open form.