Structure Elucidation - Stereochemistry

Other methods of identification include the customary preparation of derivatives, comparisons with authentic substances whenever possible, and periodate oxidation. Lately, the application of nuclear magnetic resonance spectroscopy has provided an elegant approach to the elucidation of structures and stereochemistry of various deoxy sugars (18). Microcell techniques can provide a spectrum on 5-6 mg. of sample. The practicing chemist is frequently confronted with the problem of having on hand a few milligrams of a product whose structure is unknown. It is especially in such instances that a full appreciation of the functions of mass spectrometry can be developed. 

Structure and stereochemistry of the dibromides 2a-h were elucidated by various NMR methods including ID proton-proton NOE difference spectra and 2D... 

The H and 13C NMR descriptions of a great number of perhydro-pyrrolo-oxazoles have appeared since the important contribution in the field by Meyers et al. They are mainly used for structural determination and to prove the stereochemistry of the substitution of these compounds. Some NOESY experiments were performed for the structural elucidation of diethyl (3R,5A,7aA)-5-methyl-3-phenylhexahydropyrrolo[2,l- ]-[l,3]oxazol-5-yl-phosphonate 181 <2004TL5175>. 

The fourth chapter in this volume, contributed by Helmut Duddeck, is an exceptionally thorough survey of substituent effects on carbon-13 nuclear magnetic resonance (NMR) chemical shifts. Organic chemists and others who are routinely dependent on 13C NMR for structure elucidation and for information about stereochemistry will welcome the summary presented here. Although... 

The absolute configuration of the stereo centers of vinblastine (1) was determined from the X-ray crystal structure of vincristine (2) methiodide (79,80) in view of the known relationship between 1 and 2. The absolute stereochemistry at C-I8 in vinblastine (1) and related derivatives can also be deduced by means of ORD and CD spectroscopy (81,82). The determination was made possible by the synthesis and structure elucidation of several compounds possessing the unnatural configuration at C-18 (82,84). Because this stereo center controls the relative geometry of the... 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

The various reactions of cyclopropane radical cations discussed in the preceding section have elucidated several facets of their reactivity. The results raise questions concerning the factors that determine the products observed. More significantly, we will consider whether the structures, the stereochemistry, and the chirality of the products can be related unambiguously to the structures of the radical cationic intermediates, particularly to their spin- and charge-density distributions. 

In 1996, Wu et al. isolated clausine B (80) from the stem bark of C. excavata (46). Clausine B showed inhibition of rabbit platelet aggregation and caused vasocontrac-tion. Three years later, the same group described the isolation and structural elucidation of an optically active ([a]o +159.09, c 0.0022, MeOH) carbazole alkaloid, clausine S (81) from the root bark of C. excavata. The absolute stereochemistry of clausine S is still unknown (43). 

The cytostolic phospholipase A2 inhibitor tauropinnaic acid (229) was isolated from the Okinawan bivalve Pima muricata (pen shell). The structure and stereochemistry at all but one centre were elucidated by interpretation of spectroscopic data [234]. 

There have been three reports of the same dimeric disulfide. It was first isolated from an unidentified sponge from Guam and the structure elucidated by analysis of spectral data. The (E,E) stereochemistry of the disulfide (500) was defined by comparing the I3C NMR spectroscopic data with those of the (E,Z)-isomer (501) that was obtained as an unstable minor product [425]. Compound 500 was isolated from a species of Psammaplysilla and was called psammaplin A [426]. It was also isolated from Thorectopsamma xana, collected from the same location in Guam, together with a minor dimeric metabolite bisaprasin (502). Both compounds inhibited growth of Staphylococcus aureus and Bacillus subtilis [427]. Psammaplin A (bisprasin) (500) was later isolated from a Dysidea species of sponge and shown to act on Ca2+-induced Ca2+ release channels of skeletal muscle [428]. 

The structural elucidation of the ginsenosides was challenging, but thanks to the dedicated work of Prof. Shibata (Tokyo University)2 and of Prof. Tanaka (Hiroshima University)3 their full stereochemistry is known. The ginsenosides are saponins of the dammaran class and are of two different types ... 

Structure determination of the diterpenoid alkaloids (C20) has been a challenging task because of the diverse skeleta of these alkaloids. During the period ( 1962-1972), many of the structures were determined by X-ray crystal structure determination. The development of high resolution NMR and Mass spectral instruments has facilitated the structure elucidation and determination of the stereochemistry of the diterpenoid alkaloids. The structures of more than 240 naturally occurring diterpenoid alkaloids have been determined in the past twenty five years making use of, 3C NMR studies. 

Since the late 1950s PMR spectroscopy has contributed immensely to many areas of the chemistry of alkaloids (7). With the advent of Fourier transform spectrometers CMR has rapidly approached the level of PMR in its application to problems of structural elucidation and stereochemistry. In the case of the alkaloids many classes of the isoquinoline family have been studied. These alkaloids are of particular interest not only because of their widespread occurrence in nature but also because of their pharmacological activity (2-5). Wenkert et al. (6) were the first to review progress in this area. More recently, Shamma and Hindenlang (7) have made an extensive compilation of chemical shift data on amines and alkaloids that includes many... 

Chromatography of the mother liquors of lythrancepine 102 afforded three minor alkaloids lythrancines 104, 105, and 106. The structure and stereochemistry of these bases was elucidated by analysis of NMR and mass spectra and by comparison with those of lythrancine 103. The assigned structure 104 for lythrancine-V was unequivocally confirmed by the previously described conversion of lythrancine 102 to this alkaloid via isomer 114 (61). 

Although structural elucidation of lignans is not a difficult task, the similarities between the structures can create problems. In particular, the determination of stereochemistry at the chiral center requires NOE/ NOESY NMR experiments and/or X-ray analyses. The enantiomeric excesses of the known lignans (+)-lariciresinol, (-)-secoisolariciresinol and (+)-taxiresinol, isolated from Japanese yew T. cuspidata roots, were determined by chiral high-performance liquid chromatographic analyses [78] except for (+)-pinoresinol (77% enantiomeric excess), they were found to be optically pure by Kawamura et al. In an earlier study, the presence of taxiresinol in Taxus species was reported by Mujumdar et al. [69] after they had isolated it from the heartwood of T. baccata, although they did not study its stereochemistry. 

A few years ago the complete structure of periplanone-B, apart from its stereochemistry, was elucidated and published by our research team (32,33,34) with Persoons as the principal investigator, who included this work in his doctoral thesis (35), and shared the Royal Dutch Shell Prize for 1978 with Ritter for this work and the structure elucidation of faranal, the trail pheromone of the Pharaoh s ant, Monomorium pharaonis (36,37). 

We have seen that NOESY provides information on internuclear (principally interproton) distances. For many organic molecules (as distinguished from macromolecules such as proteins and nucleic acids) structure elucidation often involves only the establishment of the structural formula and bonding scheme. However, where ambiguities in configuration or preferred conformation remain to be settled, NOESY is often crucial for establishing stereochemistry. 

The structure elucidation, mainly by chemical degradation methods, has been extensively dealt with by Battersby and Openshaw (/). There remained the problems of stereochemistry that were solved mostly in the years following the review just mentioned. They are described in Section III,D. 

Anatoxin-a, the first highly potent cyanotoxin to have its structure and absolute stereochemistry elucidated, was originally isolated from a unialgal clone of Anabaena Jlos-aquae (NRC-44h) [5]. The structure was confirmed by X-ray crystallographic data for the N-acetyl derivative [11] and additional studies have since provided further proof for the structure and stereochemistry (for example, [12]). Anatoxin-a is an unsymmetrical bicyclic secondary amine, and was the first naturally occurring alkaloid discovered to contain a 9-azabicyclo[4,2,l]nonane (homotropane) skeleton. Homotropanes are one-carbon analogs of the tropanes and, as such, are structurally closely related to the well-known alkaloid cocaine. 

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