Structural Verification

Q10. You have secured the post of Head of Structural Verification in a small pharmaceutical company (by the strategic deployment of some particularly interesting pictures of the chairman at last year s Xmas party) and you have a capital budget of 350 000 for the year. What do you spend it on ... 

This is the drug Metoprolol, a beta-blocker). Obviously, a great many deductions have to be made to arrive at a structure from scratch in this way and whilst each one in this example is valid in its own right and they all fit together perfectly well with no obvious conflicts, structural verification via the HMQC/HMBC route would be advisable ... 

The chemical reduction of 4,7-phenanthroline has been re-examined. With tin and hydrochloric acid, l,2,3,4-tetrahydro-4,7-phenanthroline predominates over the 1,2,3,4,7,8,9,10-octahydro derivative, whereas with sodium in pentanol the octahydro derivative is the principal product.246 In the course of the structural verification of these products, it has been found246 that the compound previously thought247 to be 3,8-dioxo-l,2,3,4,7,8,9,10-octahydro-4,7-phenanthroline (49) is in fact the linear diazaanthracene isomer (50) and the derived octahydro compound reported by Smith and Yu248 is likewise a diazaanthracene derivative. 

Barbuch, R. X Coutant, X E. Welsh, M. B. Setchell, K. D. 1989. The use of thermospray liquid chromatography/tandem mass spectrometry for the class identification and structural verification of phytoestrogens in soy protein preparations. Biomed. Environ. Mass Spectrom., 18, 973-977. 

Much 13C NMR data have appeared in papers concerned with the synthesis and reactivity of the six-membered sulfur heterocyclic systems over the last decade. Unfortunately, much of these valuable data are frequently relegated to the experimental section of these reports and are invariably presented as a list of unassigned chemical shifts for each compound and as such are essentially only valuable for comparative purposes and structure verification. 

It should be noted here that, currently, characterization, separation, and purification techniques of the larger cascades or dendrimers (previously discussed in earlier chapters) are straining the limits of present instrumentation. Thus, unequivocal characterization of dendritic networks is currently limited and will necessitate the development of new methods and instrumentation. However, dendritic network structural verification and elucidation should be facilitated by integration of known standard materials science methods, e.g., MS and EM. 

Stewart et al. have also reported the efforts at Molecular Nature Ltd. to generate a pure natural product library [41], Compounds for this library were isolated utilizing parallel, normal phase column chromatography followed by C-18 and/or ion exchange chromatography. To be accepted into the library, the compounds must be > 90% pure with structural verification via a combination of HPLC, NMR, MS and GC/MS. 

In many instances the spectral data of (5,5)-fused ring systems, although useful for structural verification, show no unifying features. Reference to the H NMR, 13C NMR, UV, IR and mass spectra of most (5,5)-fused heterocycles that have been examined is beyond the scope of this Chapter, but several illustrative references to spectral data that are of special value in particular applications, such as structure elucidation, are included in this section. Original publications should be consulted for data related to a particular structure. 

The IR and NMR spectra of these molecules have np unifying features. MS has been shown to be a useful technique for structural verification (77HC(30)317). 

Structural verification is based on viscosity data (indicating Einstein spheroid characteristics), elemental analyses, light-scattering experiments, and direct observation of individual dendrimers by electron microscopy. The self-limiting molar-mass ranges correspond to approximately 38 branch-cell propagations (three tiers) around a germanium initiator core. Furthermore, analysis of molecular... 

These methods were used extensively for structure verification of dendrimers prepared by the divergent initiator core method such as Starburst PAMAM [124] poly(ether) [82], and poly(ethylenimine) dendrimers [2], as well as poly(siloxane), poly(phosphonium), poly (ary lalkyl)ether, poly(arylene) and poly(arylester) dendrimers. In many cases, small-molecule model systems were used for process optimization, defect identification, and stoichiometry studies. 

Structure verification Identification of modification Purity evaluation... 

For the chemist attempting to elucidate a chemical structure, the N chemical shift is a sensitive probe of the nitrogen environment. For the purpose of structure verification, a common approach is to review the literature for related species and use their chemical shifts and couplings as models to allow estimates of these properties for the new species. While there are a number of texts, reviews, and publications available that have brought together the spectral properties of tens to hundreds of molecules, these paper-based collections are cumbersome to use when it comes to searching for a particular chemical shift or a chemical structure or... 

Naoki, H., Murata, M., and Yasumoto, T. 1993. Negative-ion fast-atom bombardment tandem mass spectrometry for the structural study of polyether compounds structural verification of yessotoxin. Rapid Commun. Mass Spectrom 7, 179-182. 

In contrast, the synthesis of the initiator functionality and the modification of the poIy(siloxane) is only one single step for TMP using an easily available diazonium compound 2 with a yield of about 60-80 %. Structure verification and determination of the initiator group content could be done by h NMR spectroscopy. GPC analysis showed that the modified poly(organosiloxane)s retain their original molecular weights. About 4-8 initiating sites have been attached onto the silicone backbone. Due to the chromophores, AMP and TMP are yellow products. 

Mass spectra of CYMS and CYMD isomers were too similar to allow distinction between their structures. In contrast, structure verification was readily obtained from NMR data. IR spectra as fingerprints for identification of the individual congeners were decisively different from each other [11]. Gas chromatographic separation of congeners was feasible with non-polar capillary columns [11,17-20]. 

TriCTAs and TeCTAs were prepared by stepwise addition of sulfuryl chloride over 4 h at 60°C. The degree of chlorination was found to be three to four (only tri- and tetrachlorinated thianthrenes were observed as reaction products) when all of the parent compound was consumed. One TriCTA and one TeCTA were obtained as main products. In addition, two other TriCTAs, four TeCTAs, and some PeCTAs were observed in minor concentrations. Because of the ortho- and para-directing properties of sulfur in electrophilic aromatic substitution reactions, 237-TriCTA and 2378-TeCTA, the thio analogue of 2378-TeCDD, were obtained as the main products. Mass spectrometry and H NMR were used in the structure verification. 

Navalainen, T., Koistinen, J., Hurnela, P. (1994) Synthesis, structure verification, and chromatographic relative retention times of polychlorinated diphenyl ethers. Environ. Sci. Technol. 28, 1341-1347. 

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