Transformation of Glycals into 2,3‐Unsaturated Glycosyl Derivatives
TL;DR: Various elimination procedures conducted on appropriate pyranoid and furanoid carbohydrate derivatives, especially on O-protected glycosyl halides afford cyclic vinyl ethers which Fischer (inappropriately) named glycals, form the major part of this chapter.
Abstract: Various elimination procedures conducted on appropriate pyranoid and furanoid carbohydrate derivatives, especially on O-protected glycosyl halides afford cyclic vinyl ethers which Fischer (inappropriately) named glycals. These are used extensively in general organic synthesis and for the preparation of non-carbohydrate natural products as well as biologically important complex carbohydrates and glycoconjugates. The best known member, tri-O-acetyl-D-glucal, is normally made from tetra-O-acetyl-alpha-D-glucopyranosyl bromide, is commercially available, and is used very frequently in this chapter to represent the family in examples of the reactions under discussion.
Because of the pronounced region- and stereoselectivities with which their addition reactions can be conducted, glycal derivatives are of major importance in synthesis. They also, however, take part in rearrangement processes that, likewise, have proved useful for synthesis. The principal one involves nucleophilic substitution of the allylic group with allylic rearrangement and results in products having double bonds in the 2, 3 positions and new substituents at the anomeric centers. By far the simplest and most commonly used way to this conversion involves the removal of the allylic substituent of the glycal and the generation of highly resonance-stabilized oxocarbenium ion intermediate. This may then react with nucleophiles at the anomeric center to give products as mixtures of diastereomers. Many examples and variations of this theme are described and form the major part of this chapter, but other ways are also considered
Almost no formal mechanistic studies have been carried out on the reactions in this chapter. Categorization of mechanism required for the treatment of this topic has been done on the basis of conditions used, product identification and largely, chemical intuition.
Keywords:
glycals;
transformation;
oxocarbenium ions;
regioselectivity;
diasterioselectivity;
nucleophilic substitutions;
homoallylic center;
addition-elimination reactions;
palladium;
leaving groups;
electrocyclic reactions;
unsaturated compounds;
free sugars;
glycosyl peroxides;
glycosyl caroxylates;
S-glycosides;
glycosyl halides;
glycosyl azides;
glycosyl phosphonates;
glycosyl hydrides;
furanoid glycols;
intramolecular applications;
reverse reaction;
reaction variations;
scope;
limitations;
configuration;
experimental procedures;
other methods
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TL;DR: This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.
Abstract: This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes. A classification of the preparative routes to these synthetic targets according to methodologies and compound categories is provided. Several of these compounds, regardless of their natural or synthetic origin, display antidiabetic properties due to enzyme inhibition (glycogen phosphorylase, protein tyrosine phosphatase 1B) or by inhibiting renal sodium-dependent glucose cotransporter 2 (SGLT2). The latter class of synthetic inhibitors, very recently approved as antihyperglycemic drugs, opens new perspectives in the pharmacological treatment of type 2 diabetes. Various compounds with the C-glycopyranosyl (het)arene motif were subjected to biological studies displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.
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TL;DR: Aus dem Dihydropyran-diol-benzaldehydacetal (Ia) erhalt man in der angegebenen Weise den als Schlusselverbindung wichtigen exocyclischen Enolether (VII) and aus ihm das Prelog-Djerassi-Lacton (VIIIb), welches Interesse bei der Synthese von Macrolid-Antibiotica besitzt as mentioned in this paper.
Abstract: Aus dem Dihydropyran-diol-benzaldehydacetal (Ia) erhalt man in der angegebenen Weise den als Schlusselverbindung wichtigen exocyclischen Enolether (VII) und aus ihm das Prelog-Djerassi-Lacton (VIIIb), welches Interesse bei der Synthese von Macrolid-Antibiotica besitzt.
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TL;DR: The reaction of α vinyl oxirane 5, prepared through a new route to the d-gulal system, with O-nucleophiles (alcohols and di-O-isopropylidene-α-d-monosaccharides) and Cn-alkyls (lithium alkyls) affords, in a completely stereoselective way, the corresponding 2-unsaturated α O- and C-glycosides having the same configuration as the starting epoxide as mentioned in this paper.
Abstract: The reaction of α vinyl oxirane 5, prepared through a new route to the d-gulal system, with O-nucleophiles (alcohols and di-O-isopropylidene-α-d-monosaccharides) and C-nucleophiles (lithium alkyls) affords, in a completely stereoselective way, the corresponding 2-unsaturated α O- and C-glycosides having the same configuration as the starting epoxide.
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References
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968 citations
TL;DR: This review provides a personal account of the explorations of a research group in oligosaccharide and glycoconjugate construction that led to novel compounds which are in the final stages of preclinical assessment.
Abstract: This review provides a personal account of the explorations of a research group in oligosaccharide and glycoconjugate construction. The journey began twenty years ago with the study of Diels–Alder reactions of complex dienes. By extending this methodology to aldehydo-type heterodienophile equivalents, access to unnatural glycals was gained (LACDAC reaction). From this point a broad-ranging investigation of the use of glycals in the synthesis of oligosaccharides and other glycoconjugates was begun. Mobilization of glycals both as glycosyl donors and glycosyl acceptors led to the strategy of glycal assembly. Several new glycosylation techniques were developed to provide practical underpinning for this logic of glycal assembly. Glycal-based paradigms have been shown to be nicely adaptable to solid phase supported synthesis. Moreover, glycal assembly—both in solution and on solid phases—has been used to gain relatively concise and efficient entry to a variety of biologically interesting and potentially valuable constructs. Some of these syntheses, particularly in the field of tumor antigens, have led to novel compounds which are in the final stages of preclinical assessment. This review presents an account of the chemical reasoning at the center of the program.
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