title: Establishing the carbon skeleton of pharmaceutical agents using HSQC-ADEQUATE spectra.
abstract: Two-dimensional NMR methods are the cornerstone of modern structure elucidation methods. When the ensemble of 1D and 2D NMR experiments normally employed for structure assignment fails, investigators typically resort to successively more complex 2D NMR experiments for structure determination and/or spectral assignment. Unsymmetrical Indirect Covariance (UIC) NMR data processing methods provide a convenient and highly efficient means of accessing the connectivity information embodied in more complex experiments such as HSQC-TOCSY spectra. Using Unsymmetrical Indirect Covariance (UIC) or General Indirect Covariance (GIC) processing to mathematically combine multiplicity-edited GHSQC and 1,1-ADEQUATE 2D NMR spectra affords an HSQC-ADEQUATE spectrum that offers a new method for establishing the carbon skeleton of a molecule. The application of this technique is demonstrated for a novel cyclin-dependant kinase inhibitor, Dinaciclib™ (SCH 727965).
authors: Merck Research Laboratories, Discovery and Preclinical Sciences - Global Chemistry, Analytical Chemistry - Structure Elucidation Group, S7-D-1-1, 556 Morris Ave., Summit, NJ 07901, United States. gary.martin2@merck.com
authors: Gary E
authors: GE
authors: Martin
authors: David
authors: D
authors: Sunseri
mesh_terms: D000465:Algorithms; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D002247:Carbon Isotopes / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003497:Cyclic N-Oxides; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D007212:Indolizines; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D008962:Models, Theoretical; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000494:pharmacology; D012984:Software; D013053:Spectrophotometry / Q000379:methods*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002247:Carbon Isotopes; D003497:Cyclic N-Oxides; D007212:Indolizines; D011726:Pyridinium Compounds; C553669:dinaciclib; D002244:Carbon; D018844:Cyclin-Dependent Kinases