Alan H. Haines

Relative Reactivities of Hydroxyl Groups in Carbohydrates

Publisher Summary This chapter discusses the important reactions of the hydroxyl group. Knowledge of the relative reactivities of hydroxyl groups in carbohydrates is fundamental to a thorough understanding of carbohydrate chemistry. The chapter explains esterification, which forms the largest part of the literature since 1953 on selective reactions of carbohydrates. The common methods of esterification utilize an acid chloride or an acid anhydride as the reagent, but other acid derivatives often show different selectivities. An investigation pertinent to the subject of favored reactivity concerned the reactions of certain acyl halides with ethanol, in acetone or chloroform solution. The mixed-order nature of some of these reactions suggested that every rate-determining transition-state contained the substrate, the nucleophile (ethanol), and an acceptor— X—for hydrogen bonding, suitable acceptors being an acetone molecule, a chloride ion, or another ethanol molecule. The possibility that intramolecular hydrogen-bonding does not persist in pyridine and that the advantage of a bonded hydroxyl group would be lost, invalidates the explanation of favored reactivity. But if the hydrogen-bonding to pyridine is hindered in the transition state, intramolecular hydrogen-bonding could conceivably assume importance.

The Selective Removal of Protecting Groups in Carrohydrate Chemistry

Publisher Summary This chapter discusses the selective introduction of substituents into carbohydrates and the hydrolysis, acetolysis, and isomerization of acetals. Of all the selective, deprotection procedures that are available to carbohydrate chemists, the partial hydrolysis of polyacetals is probably the most familiar. The acetolysis reagent trifluoroacetic- anhydride-acetic acid shows specificity similar to that of the acetic anhydride-acetic acid-sulfuric acid reagent; however, it offers the important advantage of obtaining acetatehydroxy derivatives under mild conditions because of the greater hydrolytic liability of the O-(trifluoroacetoxymethyl) group compared to the O-acetyl group. Solely on the basis of product structure, the acid-catalyzed isomerization of carbohydrate acetals occurs with favored cleavage of only one of the two acetal carbon-to-oxygen bonds. Enzymic hydrolysis can often provide the means for solving a problem involving the partial hydrolysis of esters. Relatively little work has been reported on the sequential removal of phosphate groups by chemical means from compounds containing several such groups.

The synthesis of trideoxy sugars. A preparation of rhodinose (2,3,6-trideoxy-L-threo-hexose) and methyl 2,3,6-trideoxy-α-L-erythro-hexopyranoside

Abstract A preparation of trideoxy sugars from L -rhamnose is described, which utilises, as the key step, the Corey—Winter olefin synthesis from vicinal diols. Application of this procedure to methyl 4- O -benzyl-6-deoxy-α- L -mannopyranoside, followed by reduction of the resulting olefin and hydrogenolysis of the benzyl ether group, gave methyl 2,3,6-trideoxy-α- L - erythro -hexopyranoside (the methyl glycoside of the enantiomer of amicetose). Similar treatment of methyl 4- O -benzyl-6-deoxy-α- L -talopyranoside gave methyl 2,3,6-trideoxy-α- L - threo -hexopyranoside from which rhodinose was obtained on acid hydrolysis. This constitutes the first synthesis of natural rhodinose.

Synthesis of some out,in- and out,out-macrobicyclic polyethers derived from glycerol. Out,in–in,out isomerism

Macrobicyclic polyethers containing carbon bridgeheads have been synthesised from achiral and chiral glycerol derivatives. Syntheses based on cis-1,3-O-benzylideneglycerol yield a mixture of out,out- and out, in-isomers of these macrobicyclic compounds, whereas syntheses based upon 2,3-O-isopropylidene-D-glycerol afford stereospecific routes to the out,in-isomers. 13C N.m.r. spectroscopy indicates that the out,in-macrobicyclic polyethers are undergoing out,in–in,out isomerization, and in two compounds the interconversion is slowed sufficiently on cooling for separate bridgehead carbon resonances to be observed. A rationalization is presented for the relative conformational mobility observed in the series of out,in-compounds studied. Added potassium ions produce significant changes in the 13C n.m.r. spectra of certain of the macrobicyclic polyethers, and it is suggested that these changes are a result of complexation of the cation by the bicyclic compound.

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles.

Gold nanoparticles (AuNPs), which have been widely used for the delivery of photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in aqueous solutions improving the delivery of the hydrophobic photosensitizer into the body. Furthermore, the large surface of AuNPs can be functionalized with a variety of ligands, including proteins, nucleic acids and carbohydrates, that allow selective targeting to cancer tissue. In this study, gold nanoparticles were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose derivative. For the first time, a carbohydrate was used with a dual purpose, as the stabilizing agent of the gold nanoparticles in aqueous solutions and as the targeting agent for breast cancer cells. The functionalization of the phthalocyanine-AuNPs with lactose led to the production of water-dispersible nanoparticles that are able to generate singlet oxygen and effect cell death upon irradiation. The targeting ability of lactose of the lactose-phthalocyanine functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the surface of breast cancer cells. The targeting studies showed the exciting potential of lactose as a specific targeting agent for galactose-binding receptors overexpressed on breast cancer cells.

First synthesis of (±)-1α, 2α, 4β-trihydroxycyclohex-5-ene. Anchimeric assistance in conduritol syntheses

Abstract The deoxy-conduritol (1α, 2α, 4β)-1, 2, 4-trihydroxycyclohex-5-ene ( 6 ) has been prepared in racemic form from 1, 4-benzoquinone in a six-step sequence, the key reaction involving a monohalide displacement by anchimeric assistance in the diacetoxy-dibromo compound previously employed for a synthesis of conduritol-B. Evidence for the mechanism of the double halide displacement in the latter synthesis has been obtained.

Addition Reactions with Formation of Carbon–Oxygen Bonds: (iii) Glycol Forming Reactions

The addition of hydroxy groups to the carbon–carbon double bond of an alkene (equation 1) is classed under the IUPAC nomenclature for transformations1 as a dihydroxy addition. Many reagents can bring about this transformation,2–9 which can proceed in a syn or anti manner, as shown in equation (2), and the type of addition which occurs depends on the reagent.

Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C

A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.

The Interaction of Anhydroalditols with Sweet-Almond β-glucosidase and Escherichia coli β-galactosidase: implications for the design of potent glycosidase inhibitors

Abstract A range of 1,4- and 1,5-anhydroalditols have been synthesized and assessed for their ability to inhibit glycosidases. Observed inhibition indicates that aglycone-enzyme interactions contribute significantly to both the affinity and the stereoselectivity of substrate binding. Such interactions may also contribute to enzyme-transition state interactions. Implications for the design of potent glycosidase inhibitors are discussed.

Non-equivalence of D- and L-trehalose in stabilising alkaline phosphatase against freeze-drying and thermal stress. Is chiral recognition involved?

Comparison of the ability of the enantiomeric forms of trehalose to stabilise alkaline phosphatase towards dehydration and heat showed that natural D-trehalose is superior to L-trehalose, although both disaccharides provide some protection for the enzyme. The result of this novel experiment suggests a chiral differentiation between carbohydrate and protein and thus lends support for the water replacement hypothesis of solute-based stabilisation of biomolecules, but the non-crystallinity and the physical form of the L-isomer may also be a key factor.