Structure Elucidation Group

Merck Research Laboratories, Discovery Predinical Sciences, Global Chemistry—Structure Elucidation Group, Summit, New Jersey, 07901, USA... 

Pfizer Global Research and Development, Michigan Structure Elucidation Group, Kalamazoo,... 

G. E. Martin, Michigan Structure, Elucidation Group, Pfizer Global Research and Development, Pfizer Corporation, Kalamazoo, MI 49001-0199, USA... 

The hydrides of the later main-group elements present few problems of classification and are best discussed during the detailed treatment of the individual elements. Many of these hydrides are covalent, molecular species, though association via H bonding sometimes occurs, as already noted (p. 53). Catenation flourishes in Group 14 and the complexities of the boron hydrides merit special attention (p. 151). The hydrides of aluminium, gallium, zinc (and beryllium) tend to be more extensively associated via M-H-M bonds, but their characterization and detailed structural elucidation has proved extremely difficult. 

Phosphorus NMR spectroscopy serves as a valuable diagnostic tool in the characterization and structural elucidation of primary phosphine compounds. As shown in Table 1, RPH groups resonate in the -125 ppm to -150 ppm range with direct one bond P- H coupling constants of 193-197 Hz. 

NMR spectroscopy of these phosphorus complexes has been used for structure elucidation. Depending on the bulkiness of the thiourea substituents, a single isomer (bulky) or two isomers (small size, example in Scheme 11 with two possibihties for the relative position of the cyano group)... 

In view of the limited capacity of the sulfur atom in the sulfoxide and sulfone functional groups to transmit conjugative effects due to the insulating effect of the LUMO sulfur d-orbitals , the application of the UV technique even in the case of the cyclic vinyl sulfones (e.g. thiete dioxides 6b) cannot be expected to find extensive use. UV spectra of substituted thiete dioxides in which an extended conjugated system (e.g. 194) exists in the molecule, did provide useful information for structure elucidation . However, the extent... 

Preparative-scale fermentation of papaveraldine, the known benzyliso-quinoline alkaloid, with Mucor ramannianus 1839 (sih) has resulted in a stereoselective reduction of the ketone group and the isolation of S-papaverinol and S-papaverinol M-oxide [56]. The structure elucidations of both metabolites were reported to be based primarily on ID and 2D NMR analyses and chemical transformations [56]. The absolute configuration of S-papaverinol has been determined using Horeau s method of asymmetric esterification [56]. The structures of the compounds are shown in Fig. 7. 

Table VII gives a survey of alkaloids that exhibit the hasubanonine-type cleavage. The characteristic fragmentation pattern of this group, possessing an a,/ -unsaturated carbonyl group in ring C, is significantly different from other groups. In the case of hasubanonine (5) (3), the most abundant and nitrogen-free ion peak was observed at m/z 315, which is important for structure elucidation of this group (2,73).

Potassium borohydride reduction of runanine (17) yielded dihydro-runanine (24), the H-NMR spectrum of which (Table II) exhibited a triplet (64.25), the proton bearing the hydroxyl group coupling with those of C-5 (35). The optical activity of runanine (17), [a]D —400°, was similar to that of hasubanonine (5), [a]D —214° (3) therefore, it was concluded that the ethylamine linkage must have the same configuration as hasubanonine [C-13 (R) and C-14 (S)]. From these results, structure 17 was proposed for runanine (35) however, no application of mass spectral data to the structure elucidation was presented (35). 

The structure elucidation of the kinamycins was a formidable challenge, and the information presented below draws from the work of several research groups over a period of more than 20 years. As will be shown, the originally proposed structure of the kinamycins contained a cyanamide rather than a diazo function. Subsequent synthetic and biosynthetic studies led to replacement of the cyanamide with a diazo function. The structural elucidation was challenging, in part, because of the high degree of unsaturation of the kinamycins, which limits the utility of H and 2D NMR analysis. In addition, because these structures were unprecedented, there were no clear benchmarks for comparison at the time. The pathway from isolation to determination of the correct structure is described below. 

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