Stereochemistry spectroscopic methods

Other spectroscopic methods such as infrared (ir), and nuclear magnetic resonance (nmr), circular dichroism (cd), and mass spectrometry (ms) are invaluable tools for identification and stmcture elucidation. Nmr spectroscopy allows for geometric assignment of the carbon—carbon double bonds, as well as relative stereochemistry of ring substituents. These spectroscopic methods coupled with traditional chemical derivatization techniques provide the framework by which new carotenoids are identified and characterized (16,17). 

Organic chemists who read this book and do the problems as they occur in the text will be rewarded with a functional understanding of NMR spectroscopy at a level that will allow them to make full use of this most versatile spectroscopic method for investigating the structures, stereochemistries, and conformations of organic molecules. 

The 20-acetoxy derivatives of clavulones I, II and III (92-94) were reported shortly afterward with their structures being determined by spectroscopic methods [120]. A 4R and 12S (again, the incorrect 12R stereodescriptor was applied) stereochemistry in these three new compounds was deduced by the close comparability of their CD spectra with those obtained for clavulones I, II, and III (88-90). 

Dehydrodarlingianine (69) and dehydrodarlinine (72) were synthetized by base-catalyzed reaction of hygrine with cinnamaldehyde and benzaldehyde, respectively. The relative stereochemistry of darlingianine (65) was established by X-ray diffraction (111). The structure of the other bases was established by chemical correlations as well as by spectroscopic methods. The absolute configurations of these bases remain to be determined. 

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

A further cytotoxic, octapeptide, patellamide E (40), was isolated from L patella from Singapore and the structure was elucidated by chemical and spectral methods [75]. Patellamide F (41) was isolated from L. patella from north-western Australia and was also cytotoxic. The structure and absolute stereochemistry of patellamide F (41) were established by chemical and spectroscopic methods. Patellamide B (22), ulithiacyclamide (16) and lissoclinamide 3 (19) were also isolated from the same sample [76]. The octapeptides, patellamide G (42) and ulithiacyclamides E-G (43-45) were isolated from L. patella from Pohnpei, along with known series members [77]. 

The theonezolides are 37-membered macrocycles, consisting of fatty acid chains with attached functionalities such as a sulfate ester and a thiazole [22]. Theonezolide A (610) is a cytotoxic metabolite of Theonella sp. from Okinawa. The structure was reported without stereochemical details [489]. The structures of theonezolides B (611) and C (612) from a Japanese Theonella sp. were determined by spectroscopic methods but without stereochemistry, except at one centre [490]. 

Dimerization of tetraacetylethylene (18) has led to spirofuran (19), whose structure was established by X-ray analysis (80CJC1645). A possible mechanistic pathway for its formation would involve the dimerization of an intermediate (20) which could account for the stereochemistry of the dimer (19) (Scheme 4). The same furan (21) is a possible intermediate in the formation of 3,4-diacetyl-2-halomethyl-5-methylfuran (22) from (18) with concentrated halo acids (70JCS(C)1536). The structures of the furans (22) were established by chemical and spectroscopic methods. 

The structures of these compounds were assigned primarily by spectroscopic methods. The recrystalization of the natural Et A12-oxide (67) and the 21 -G-methyl-A12-formyl derivative of compound 63 gave single crystals and allowed X-ray analysis of these systems [74]. The absolute stereochemistry of 70 was determined by chiral GC of the L-Cys unit and by ROESY spectrum of its acetyl derivative [75]. The structures of Et s are related to the microbially derived safracins and saframycins -antitumor agents first isolated from cultured Streptomyces species [76] -as well as to the sponge metabolites renieramycin and xestomycin [77]. 

This is the first of two review chapters on spectroscopic methods taken as a whole. In Chapter 32 we shall tackle the complete identification of organic compounds including the vital aspect of stereochemistry, introduced in Chapters 16 and 19. In this chapter we gather together some of the ideas introduced in previous chapters on spectroscopy and mechanism and show how they are related. We shall explain the structure of the chapter as we go along. 

No one argued with this structure because it was determined by reliable spectroscopic methods— NMR plus an X-ray crystal structure of a derivative. This was not always the case. Go back another 25 years to 1946 and chemists argued about structures all the time. An undergraduate and an NMR spectrometer can solve in a few minutes structural problems that challenged teams of chemists for years half a century ago. In this chapter we will combine the knowledge presented systematically in Chapters 3,11, and 15, add your more recently acquired knowledge of stereochemistry (Chapters 16, 18, and 31), and show you how structures are actually determined in all their stereochemical detail using all the evidence available. 

Basic structure (Chapters 4 and 11) and stereochemistry (Chapter 32) by spectroscopic methods... 

The elucidation and confirmation of structure should include physical and chemical information derived from applicable analyses, such as (a) elemental analysis (b) functional group analysis using spectroscopic methods (i.e., mass spectrometry, nuclear magnetic resonance) (c) molecular weight determinations (d) degradation studies (e) complex formation determinations (f) chromatographic studies methods using HPLC, GC, TLC, GLC (h) infrared spectroscopy (j) ultraviolet spectroscopy (k) stereochemistry and (1) others, such as optical rotatory dispersion (ORD) or X-ray diffraction. 

Tilidine is the minor component of the product of cycloaddition of trans 1-dimethylamino-l,3-butadiene (21a, R = NMe2) to ethyl atropate, a reaction with favored cis stereochemistry. When the butadiene 21a (R = NHC02CH2CC13) was employed, the trans isomer was obtained exclusively and was converted to tilidine in two steps (Zn dust-HAc followed by CH20-NaBH4).(35) Stereochemistry in the series was established by spectroscopic methods, X-ray crystallography, and chemical transformations. t-l-Dimethyl-amino-r-3-propionyloxy-3-phenylcyclohexane, a saturated reversed-ester analog of tilidine, was only feebly active in the MHP test.(62)... 

The book is divided into three parts. Part I deals with typical complex organic reactions such as (i) reactions involving carbocations and carbanions, (i/) Pericyclic and electrocyclic reactions and (ii/) Sigmatropic and Chelotropic reactions. This part also includes material useful for characterization of products from structural point of view such as Geometrical isomerism, Stereochemistry and Conformation. Part II is concerned with spectroscopic methods of structure determination such as U.V.,... 

Nuclear magnetic resonance (NMR) spectroscopy is the most powerful spectroscopic method for structural elucidation of organic molecules and is routinely used by organic chemists. Summarised below are common NMR active nuclei chemical shift data for NMR solvents, common impurities, and functional groups coupling constants and details of common NMR experiments used to determine the connectivity and stereochemistry of small organic molecules. 

Intramolecular conjugate addition of a chiral amine group to an a,/J-unsaturated enone has rarely been described. One example is the synthesis of the Amaryllis alkaloid (4 )-maritidinel6. Asymmetry is induced by L-tyrosine as starting material, and in the key reaction the secondary amino group (prepared in situ) adds to the dienone moiety giving exclusively one diastereomer 2 in 41 % yield. Characterization is by spectroscopic methods (NMR, IR, MS) and the stereochemistry is verified by conversion of 2 to (+ )-epimaritidine, and subsequently (+ )-maritidine, the absolute configuration of which is known. 

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