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Unequivocal location of sites of N ‐oxidation using natural abundance long‐range 1 H, 15 N GHNMQC two‐dimensional NMR
Author(s) -
Farley Kathleen A.,
Bowman Phil B.,
Brumfield Jay C.,
Crow Frank W.,
Duholke Wayne K.,
Guido Jane E.,
Robins Russell H.,
Sims Sandra M.,
Smith Richard F.,
Thamann Thomas J.,
Vonderwell Brenda S.,
Martin Gary E.
Publication year - 1998
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199806)36:13<s11::aid-omr275>3.0.co;2-r
Subject(s) - chemistry , chemical shift , piperazine , heteronuclear molecule , nitrogen , carbon 13 nmr , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
A method is described for unequivocally establishing the site of N ‐oxidation which relies on the relatively large downfield shift of aliphatic nitrogen resonances following oxidation. The technique described is based on 15 N at natural abundance and does not require labelling. 15 N chemical shifts are established on the basis of long‐range 1 H– 15 N heteronuclear coupling pathways detected via two‐dimensional NMR using the GHNMQC pulse sequence. The oxidized nitrogen in the two piperazine‐containing systems studied was shifted downfield by approximately +68 ppm; the opposite, non‐oxidized nitrogen in the piperazine ring was shifted upfield by an average of ‐6 ppm ( 15 N chemical shifts are referenced to liquid ammonia with a chemical shift of 0 ppm). N ‐oxidation perturbations in 15 N chemical shifts were first parameterized using an oxazolidinone antibiotic (eperezolid) and its N ‐oxide as a model system. After the 15 N shift due to N ‐oxidation was determined, the method was used to establish unequivocally the site of N ‐oxidation in PNU‐101387, a piperazine‐containing anxiolytic agent. Conventional spectroscopic methods were equivocal and could not reliably establish the site of N ‐oxidation. © 1998 John Wiley & Sons, Ltd.