Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters (original) (raw)
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IntechOpen eBooks, 2023
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The plasma membrane of cells contains a diverse array of lipids that provide important structural and biological features. Glycolipids are typically a minor component of the cell membrane and consist primarily of glycosphingolipids (GSLs). GSLs in vertebrates contain a multifarious assortment of glycan headgroups, which can be important to biological functions based on lipidlipid and lipid-protein interactions. The design of probes to study these complex targets requires advanced synthetic methodologies. In this review, we will discuss recent advances in chemical and chemoenzymatic synthesis of GSLs in conjunction with the use of these approaches to design new probes. Examples using either chemical or enzymatic semisynthesis methods starting from isolated GSLs will also be reviewed. Focusing primarily on vertebrate glycolipids, we will highlight examples of radionuclide, fluorophore, photoresponsive, and bioorthogonal tagged GSL probes. 10 Table 2. Svennerholm's ganglioside nomenclature a Name Structure (condensed form) Symbol nomenclature b,20 Total syntheses c GM4 Neu5Ac(α2-3)Gal(β1-1')Cer α3 Cer β 27 Reviewed in 26 GM3 Neu5Ac(α2-3)Gal(β1-4)Glc(β1-1')Cer β4 α3 Cer β 28-36 Reviewed in 26,37,38 GM2 GalNAc(β1-4)[Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 α3 Cer β 39,40 Reviewed in 26,37 GM1 d Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 Cer β 41-43 Reviewed in 26 GM1b e Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 Cer β Reviewed in 26 Fuc-GM1 Fuc(α1-2)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α2 Cer β Reviewed in 37 GD3 Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-4)Glc(β1-1')Cer β4 α3 α8 Cer β 44-47 Reviewed in 26 GD2 GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 α3 α8 β4 Cer β Reviewed in 26 GD1a Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 Cer β 42 Reviewed in 26,37 GD1b Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 α3 α8 β4 β3 Cer β Reviewed in 26 Fuc-GD1b Fuc(α1-2)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 α3 α8 β4 β3 α2 Cer β GT3 Neu5Ac(α2-8)Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-4)Glc(β1-1')Cer β4 α3 α8 α8 Cer β Reviewed in 26 Name Structure (condensed form) Symbol nomenclature b,20 Total syntheses c GT1a Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 Cer β 42 Reviewed in 26,37 GT1b Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 Cer β Reviewed in 26 GT1c Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α8 α8 Cer β GQ1b Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 α8 Cer β 48 Reviewed in 26 37,38 GQ1c Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 α8 Cer β GP1b Neu5Ac(α2-8)Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 α8 α8 Cer β GP1c Neu5Ac(α2-8)Neu5Ac(α2-3)Gal(β1-3)GalNAc(β1-4)[Neu5Ac(α2-8)Neu5Ac(α2-8)Neu5Ac(α2-3)]Gal(β1-4)Glc(β1-1')Cer β4 β4 β3 α3 α3 α8 α8 α8 Cer β 49 a Nomenclature from Svennerholm, L. Progress in Brain Research 1994, 101, xi-xiv. b The key for the Symbol Nomenclature for Glycans (SNFG) is provided in Figure 2. c References for the synthesis of each lipid, or reviews thereof. d Also called GM1a e Also called cisGM1. 13,24 While gangliosides are defined by the presence of at least one sialic acid residue, there are multiple forms of sialic acid (Neu5Ac) that may occur in vertebrates. The most predominant of
A new approach to the synthesis of glycosides
Pure and Applied Chemistry, 1993
An new approach towards glycosides, which obviates the use of promoters and depends upon the acihty of the glycosyl acceptor is proposed to achieve regioselective glycosidation. Glycosylidene mbenes, generated under thermal or photolytic conditions from 0benzylated or 0-acylated 1-azi-glycoses, or from glycono-l,5-(or 1,4)-lactone tosylhydrazones react with hydroxy compounds to yield glycosides. The preparation of these precursors, their structure, their thermal stability, and their products of thermolysis are discussed. A mechanism is proposed to explain and predict the reaction of 1-azi-glycoses with mono-, di-, and triols. Protonation of the carbene in the o-plane leads to an ion-pair, which cannot immediately form glycosides. The fate of this ion pair depends upon the pK of the glycosyl acceptor, inter-and intramolecular hydrogen bonds, the direction of H-bonds, the presence of a neighbouring group at C(2), the configuration of the glycosyl acceptor, the solvent, and the temperature. Strongly acidic hydroxy compounds give glycosides in high yields and stereoselectively. Successful regio-and stereoselective glycosidation of diols and triols depends strongly upon intra-(and inter)molecular hydrogen bonds, both between the hydroxy goups of the acceptor and between functional groups of the donor and hydroxy groups of the acceptor. This is illustrated by a number of significant cases. For some of them, regioselectivity is complementary to the one observed in glycosidations of the Koenigs-Knorr-type, for others it is not. Reasons for this are discussed. Other cases present the preferential glycosylation of secondary hydroxy groups in the presence of a primary one, and the selective formation of aD -glycosides of M A C and GlcNAc. Intramolecular reactions of alkoxyalkyl carbenes are illustrated by a new method for the formation of benzylidene acetals under basic conditions, and by a new synthesis of homobenzofurans. New reactions, leading to the formation of C,C bonds at the anomeric centre are presented: the synthesis of spiro-oxiranes, of dialkoxy-spiro-cyclo opanes, and of the first glycosylated, enantiomdcally pure derivatives of Cmbuckminst&erene.
One-Pot Syntheses of Immunostimulatory Glycolipids
The Journal of Organic Chemistry, 2010
Glycolipids containing α-linked galactosyl and glucosyl moieties have been shown to possess unique immunostimulatory activity creating a need for access to diverse and anomerically pure sources of these compounds for immunological studies. To meet this demand, glycosyl iodides were enlisted in the synthesis of these biologically relevant glycoconjugates. In the first generation protocol per-O-benzyl galactosyl iodide was efficiently coupled with activated sphingosine acceptors, but fully functionalized ceramides were found to be unreactive. To overcome this obstacle, per-O-trimethylsilyl glycosyl iodides were investigated and shown to undergo highly efficient coupling with ceramide and glycerol ester acceptors. Contrary to what has been observed with other donors, we detected little difference between the reactivity of glucosyl and galactosyl iodides. The trimethylsilyl protecting groups play a dual role in activating the donor toward nucleophilic attack while at the same time providing transient protection: the silyl groups are readily removed upon methanolysis. All reactions proceeded with complete acceptor regioselectivity, eliminating the need for additional protecting group manipulations, and the desired α -anomers were formed exclusively. This three step one-pot synthetic platform provides rapid access to an important class of immunostimulatory molecules including the first reported synthesis of the glucosyl analog of the bacterial antigen BbGL-II.