Organic Structure Elucidation Strategies

Most chemists need to be able to solve structure problems What compound will fit the spectral data A proper attitude toward this type of problem solving is needed, and nobody has said it better than Sherlock Holmes It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts. Strategies are definitely needed. Generate possibilities, then select the best one that fits the data. If none fit, generate more possibilities and examine your assumptions. 

Spectra problems are much like jigsaw puzzles. The first step is to find all the pieces, spread them out, and look at them. The next step is usually to find all the pieces that make up the border of the puzzle. Then pieces adjacent to the border are filled in, moving toward the center until the puzzle is complete. Don t hammer home any pieces. The most conunon error is to try to put the puzzle together before identifying all the pieces. Make sure you understand all the parts of the puzzle before trying to put it together. You will have to maintain flexibility so that you don t lock yourself out of the correct answer. Structure elucidation also is like a medical diagnosis if it does not fit all the facts and make sense, it s probably incorrect. 

The first piece of information we try to get is the molecular formula from the mass spectral formula weight and the percent composition from a combustion analysis if available. If we don t have a molecular formula, we can still get a minimum count on the number of carbons and hydrogens from the NMR spectra, which will be discussed later. 

Even with a lower-resolution mass spectrometer we can get hints about the elemental composition. Molecular ions (M) have higher weight peaks at M+1, M+2 due to minor isotopes, which can tip you off to their presence. Common examples are shown below (with the intensity of the taller peak set at 100%). Hydrogen, nitrogen, oxygen, fluorine, and iodine have no significant isotope peaks ( 0.4%). The presence of chlorine or bromine is important to identify in the mass spectrum. 

Whether the molecular weight is odd or even is an important clue. The molecular ion will have an even molecular weight unless it contains an odd number of nitrogen atoms. The presence of one nitrogen atom allows an additional hydrogen atom in the molecular formula, making the weight odd. 

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The unique molecular skeleton of the C-nor-D-homosteroids represents significant challenges for organic chemists. The structure elucidation and the total synthesis of cyclopamine (3, also known as 11-deoxojervine), jervine (ll-oxo-3), and veratramine (4) are important milestones in steroid chemistry. Many synthetic strategies were developed in the 1960s-1970s for these targets. Notably, Masamune... 

Gorog, S. Identification, structure elucidation and determination of related organic impurities 2.1. Strategies in impurity profiling. Prog. Pharm. Biomed. Anal. 4 67-83, 2000. 

Actual case studies using these isolation and syntheses as well as mass spectral and NMR approaches are outlined in the remainder of this chapter. This collaborative multidisciplinary strategy is applied to the structure elucidation of all the impurity and degradant case studies presented. The successful elucidation of these structures was essential to predict potential toxicity, set threshold limits, and identify ways to prevent or greatly reduce their formation. The case studies have been organized into degradation and process-related impurities examples. 

Strategies for NMR spectroscopic structure elucidation of organic compounds have been reviewed extensively.34-37 In this section, we briefly describe a set of the most commonly useful 2D NMR spectra that is sufficient for most (though certainly not all) organic structure determination problems, and we comment on specific modifications of acquisition parameters that facilitate the analysis of mixtures. 

Kwan EE, Huang SG (2008) Structural elucidation with NMR spectroscopy practical strategies for organic chemists. Eur J Org Chem 2008 2671-2688. doi 10.1002/ ejoc.200700966... 

Mass spectra of chemical compounds have a high information content. This article describes computer-assisted methods for extracting information about chemical structures from low-resolution mass spectra. Comparison of the measured spectrum with the spectra of a database (library search) is the most used approach for the identification of unknowns. Different similarity criteria of mass spectra as well as strategies for the evaluation of hitlists are discussed. Mass spectra interpretation based on characteristic peaks (key ions) is critically reported. The method of mass spectra classification (recognition of substructures) has interesting capabilities for a systematic structure elucidation. This article is restricted to electron impact mass spectra of organic compounds and focuses on methods rather than on currently available software products or databases. 

Evidence has accumulated that inhibition of QS is a strategy commonly adopted by eukaryotic organisms to combat potentially pathogenic bacteria. The production of AHL antagonists has been demonstrated for the marine red alga Delisea pulchra [68], higher plants [85] as well as the animal Flustra foliacea [ 127]. Compounds with QS-inhibiting activity have been obtained from D. pulchra and F. foliacea (Fig. 5) while the structures of the plant-derived substances have yet to be elucidated. 

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