title: Using HMBC and ADEQUATE NMR data to define and differentiate long-range coupling pathways: is the Crews rule obsolete?
abstract: It is well known that as molecules become progressively more proton-deficient, structure elucidation becomes correspondingly more challenging. When the ratio of (1)H to (13)C and the sum of other heavy atoms falls below 2, an axiom that has been dubbed the "Crews rule" comes into play. The general premise of the Crews rule is that highly proton-deficient molecules may have structures that are difficult, and in some cases impossible, to elucidate using conventional suites of NMR experiments that include proton and carbon reference spectra, COSY, multiplicity-edited HSQC, and HMBC (both (1)H-(13)C and (1)H-(15)N). However, with access to modern cryogenic probes and microcyroprobes, experiments that have been less commonly utilized in the past and new experiments such as inverted (1)J(CC) 1,n-ADEQUATE are feasible with modest sized samples. In this light, it may well be time to consider revising the Crews rule. The complex, highly proton-deficient alkaloid staurosporine (1) is used as a model proton-deficient compound for this investigation to highlight the combination of inverted (1)J(CC) 1,n-ADEQUATE with 1.7 mm cryoprobe technology.
authors.affiliation: Discovery and Preclinical Sciences, Process and Analytical Chemistry, Structural Elucidation Group, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Senior
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Williamson
authors.forename: Gary E
authors.initials: GE
authors.lastname: Martin
mesh_terms: D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards*; D008962:Models, Theoretical; D015394:Molecular Structure; D011522:Protons; D012015:Reference Standards; D013331:Strychnine / Q000737:chemistry*
chemical_list: D011522:Protons; D013331:Strychnine