Spectroscopy natural products

Jaspars, M. 1999. Computer assisted structirre elucidation of natural products using two-dimensional NMR spectroscopy. Natural Product Reports, 16, (2), 241 248. 

Generally, the most powerful method for stmctural elucidation of steroids is nuclear magnetic resonance (nmr) spectroscopy. There are several classical reviews on the one-dimensional (1-D) proton H-nmr spectroscopy of steroids (267). C-nmr, a technique used to observe individual carbons, is used for stmcture elucidation of steroids. In addition, C-nmr is used for biosynthesis experiments with C-enriched precursors (268). The availability of higher magnetic field instmments coupled with the arrival of 1-D and two-dimensional (2-D) techniques such as DEPT, COSY, NOESY, 2-D J-resolved, HOHAHA, etc, have provided powerful new tools for the stmctural elucidation of complex natural products including steroids (269). 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

The geometries of oxiranes have been determined mainly by X-ray diffraction on crystalline natural products, the oxirane ring being widespread in nature (Section 5.05.5.3). However, the detailed structure of the parent compound (Figure 1) has been secured by microwave spectroscopy and electron diffraction studies (64HC(l9-l)l). The strain in this... 

Indeed, great emphasis was placed on the presentation of compounds in crystalline form for many years, early chromatographic procedures for the separation of natural substances were criticized because the products were not crystalline. None the less, the invention by Tswett (3) of chromatographic separation by continuous adsorption/desorption on open columns as applied to plant extracts was taken up by a number of natural product researchers in the 1930s, notably by Karrer (4) and by Swab and lockers (5). An early example (6) of hyphenation was the use of fluorescence spectroscopy to identify benzo[a]pyrene separated from shale oil by adsorption chromatography on alumina. 

Solving Problems with NMR Spectroscopy is a very welcome addition to the existing literature. It fulfills a real need for an up-to-date and authoritatively written introduction for students and practitioners of NMR. The vast experience of Professor Atta-ur-Rahman and Dr. Muhammad Iqbal Choudhary in the field of structural natural-product chemistry combined with a profound understanding of the concepts and techniques of NMR has led to a very useful and reliable treatise of practical NMR that is useful both for graduate students and for research workers. Professor Atta-ur-Rahman and Dr. Muhammad Iqbal Choudhary are congratulated for their admirable achievement. 

It is my opinion that this approach has considerable merit, provided that the questions posed in the problems are wisely selected, as indeed they are in this text. The authors themselves are well versed in natural-product chemistry, an area that presents a wide array of small molecule structural problems. They are therefore concerned that the reader reach the practical goal of applying the full power of NMR spectroscopy to problems of this type. To this end they have selected problems that address methods for solving structures as well as those that pertain to basic theory. The authors have wisely made a point of treating the more widely used ID and 2D experiments in considerable detail. Nevertheless, they also introduce the reader to many of the less common techniques. 

Although saponification was found to be unnecessary for the separation and quantification of carotenoids from leafy vegetables by high performance liquid chromatography (HPLC) or open column chromatography (OCC), saponification is usually employed to clean the extract when subsequent purification steps are required such as for nuclear magnetic resonance (NMR) spectroscopy and production of standards from natural sources. 

In summary, NMR spectroscopy is an extremely versatile tool useful that enables researchers to understand the structure of natural products such as carotenoids. For a full structural assignment, the compound of interest has to be separated from coeluents. Thus, it is a prerequisite to employ tailored stationary phases with high shape selectivity for the separation in the closed-loop on-line LC-NMR system. For the NMR detection, microcoils prove to be advantageous for small quantities of sample. Overall, the closed-loop system of HPLC and NMR detection is very advantageous for the structural elucidation of air- and UV-sensitive carotenoids. 

The possible occurrence of such major rearrangement of a compound s carbon skeleton, during the course of apparently unequivocal reactions, is clearly of the utmost significance in interpreting the results of experiments aimed at structure elucidation particularly when the actual product is isomeric with the expected one. Some rearrangements of this type are highly complex, e.g. in the field of natural products such as terpenes, and have often made the unambiguous elucidation of reaction pathways extremely difficult. The structure of reaction products should never be assumed but always confirmed as a routine measure lH and 13C n.m.r. spectroscopy have proved of enormous value in this respect. 

Another case is where the chemistry is known, but the spectroscopy is unknown, because the pure material is not available. Protein, for example, cannot be extracted from wheat (or at least not and still remain protein), so the spectrum of pure protein as it exists in wheat is unknown. Even simpler molecules are subject to this effect we can measure the spectrum of pure water easily enough, for example, but that is not the same spectrum as water has when it is present as an intimate mixture in a natural product -the changes in the hydrogen bonding completely change the nature of the spectrum. 

J. Schmidt and S. Huneck, Mass spectroscopy of natural products. V. Mass spectroscopic studies of ring A substituted allobetulane derivatives, Org. Mass Spectrom., 14, 646 655 (1979). 

LC-NMR plays a central role in the on-line identification of the constituents of crude plant extracts (Wolfender and others 2003). This technique alone, however, will not provide sufficient spectroscopic information for a complete identification of natural products, and other hyphenated methods, such as LC-UV-DAD and LC-MS/MS, are needed for providing complementary information. Added to this, LC-NMR experiments are time-consuming and have to be performed on the LC peak of interest, identified by prescreening with LC-UV-MS. NMR applied to phenolic compounds includes H NMR,13 C NMR, correlation spectroscopy (COSY), heteronuclear chemical shift correlation NMR (C-H HECTOR), nuclear Overhauser effect in the... 

The N-oxide of the alkaloid dihydrocorynantheol (21) has also been mentioned as a natural product from the leaves of Mitragyna parvifolia (Roxb.) Korth. however, it was detected only by mass spectroscopy and no further evidence for the structure has been given (31). 

Within the past two decades, the importance of nuclear magnetic resonance (n.m.r.) spectroscopy has enlarged tremendously. Its advantages over other methods in the structural and conformational analysis of such complex molecules as natural products, and particularly with regard to the still-increasing importance of medical investigations using n.m.r. techniques, is abundantly evident. Because destruction of the sample is avoided, different n.m.r. experiments can be performed repeatedly, and... 

Natural products, from plants and foods to rocks and minerals, are complicated systems, but their analysis by Raman spectroscopy is a growing area. Most examples come from quality control laboratories, motivated to replace current time-consuming sample preparation and analysis steps with a less labor-intensive, faster technique but most authors anticipated the eventual application to process control. Often a method will be practiced in a trading house or customs facility to distinguish between items perceived to be of different qualities, and thus prices. 

Complete structure elucidation of individual resin glycoside constituents is now achieved readily by the use of a combination of high-resolution mass spectrometry and NMR spectroscopy. These methods are applicable to the isolated natural products or to their peracetylated and methylated derivatives. 

Reynolds FR, Enriquez RG, Choosing the best pulse sequences, acquisition parameters, postacquisition processing strategies, probes for natural product structure by NMR spectroscopy, JNat Prod 65 221—244, 2002. 

As is the case with many natural products isolated in the last 25 years, H-NMR spectroscopy has played a major role in the structural elucidation of the... 

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