Natural products using carbohydrates

Advances in total synthesis and development of natural products using carbohydrates 97YGK970. 

Recent Progress in Total Synthesis and Development of Natural Products Using Carbohydrates... 

Table 3. Fluorination of Hydroxy Groups in Carbohydrates, Nucleosides, Steroids, and Natural Products Using (Dialkylamino)trifluoro-/. -sulfanes...

Review coverage of the chemistry involved in the synthesis of enantiomerically pure natural products from carbohydrates is now extensive [2]. It is relevant to note that whereas, in 1983, the numbers of carbocyclic target compounds were relatively limited, as outlined in an authoritative monograph written by Hanessian [3], a comprehensive review of the methods available for making cyclopentane and cyclohexane derivatives from carbohydrates published 10 years later [4] cited 338 references, more than 80% of which were dated 1980 or later. The attention afforded the synthesis of carbocyclic products also features prominently iu a 1993 review of the use of sugars in the preparation of enantiomerically pure natural products [2],... 

Hanessian, S, Approaches to the total synthesis of natural products using chiral templates derived from carbohydrates, Acc. Chem. Res., 159-165, 1979. 

A comprehensive review has appeared this year on the conversion of carbohydrate derivatives to functionalized cyclopentanes and cyclohexanes, and another review has described the synthesis of natural products from carbohydrates using the Perrier rearrangement.2 (+)-Methyldihydroepijasmonate 2 has been prepared from levoglucosenone (Scheme 1). The n-pentyl group was introduced by stereoselective cuprate addition, and the carbocyciic ring was formed via 5-exo-trig alkylation of the enolate derived from 1 (Scheme 1)2... 

Recently, Trost and Hembre reported a concise asymmetric synthesis of (+)-cyclophellitol based on the Pd-catalyzed kinetic resolution of racemic conduritol B tetraacetate using the chiral ligand (R,R)A. Most syntheses have started with enantiomerically pure natural products, notably carbohydrates. Such a strategy normally entails rather a long route. A pivalate was chosen as the carboxylate nucleophile for the resolution because the resultant allyl pivalate was anticipated to ionize much more slowly than the starting material. The tetraacetate ( )-conduritol was synthesized from benzo-quinone the kinetic resolution was carried out using 0.65 equiv of sodium pivalate with 1 mol % of (i7 -C3H5PdCl)2 and 3 mol % of (R,R)-AA in a two-phase system with tetra-hexylammonium bromide as the phase transfer catalyst. 

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. 

Many classes of natural product possess heterocyclic components (e.g. alkaloids, carbohydrates). However, their structures are often complex, and although structure-based names derived by using the principles outlined in the foregoing sections can be devised, such names tend to be impossibly cumbersome. Furthermore, the properties of complex natural product structures are often closely bound up with their stereochemistry, and for a molecule containing a number of asymmetric elements the specification of a particular stereoisomer by using the fundamental descriptors (R/S, EjZ) is a job few chemists relish. 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

Note. In carbohydrate nomenclature, substitution at a heteroatom is normally indicated by citing the locant of the attached carbon atom, followed by a hyphen, and then the italicized heteroatom element symbol, e.g. 2-0-methyl, 5-N-acetyl. Substituents on the same kind of heteroatom are grouped (e.g. 2,3,4-tri-0-methy 1), and substituents of the same kind are cited in alphabetical order of heteroatoms (e.g. 5-N-acetyl-4,8,9-tri-0-acetyl). The alternative format with superscript numerical locants (e.g, N5,(/,(), ( -tetraacetyl), used in some other areas of natural product chemistry, is unusual in carbohydrate names. 

This series in heterocychc chemistry is being introduced to collectively make available critically and comprehensively reviewed hterature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituents hemoglobin and purines, as well as pyrimidines, are constituents of nucleic acid (DNA and RNA). Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers, and the in dye industry as dyes, etc. 

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