Fluorinated carbohydrates. Part VI. Studies of derivatives of 3-deoxy-3-fluoro-<scp>D</scp>-galactose

Brimacombe, J. S.; Foster, A. B.; Hems, R.; Westwood, J. H.; Hall, Len

doi:10.1139/v70-660

Cited by 33 publications

(9 citation statements)

References 5 publications

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“…Comparison of these couplings with those obtained from the arabino-hexose family (4,5,6) indicates that the molecule shifts its conformational preference after acetylation, from the Vo p 'To p 'V of the parent to 'To p 'V P 'T2 of the derivative. Similar results are obtained for the benzoylated derivative, but not for 3-fluoro-3-deoxy-l,2;5,6-di-0-isopropylidene-u-D-galactose (12). Little information can be gained from the sparse results on the 3-keto compounds.…”

Section: Acetyl and Keto Derivativessupporting

confidence: 58%

“…results obtained from this compound indicate that 3-deoxy-ribo-hexose (10) has the 'T,e V, .+ 0T4 conformational preference. The similarity of the couplings reported in Table 2 indicates that the endo (11) and exo (12) hydroxylated derivatives of 3-deoxy-ribo-hexose (10) have This orientation of the hydroxyl group and the suggested conformation are completely consistent with the proposed hydrogen bond formation between the C-3 hydroxyl and the C-2 oxygen of the 1,3-dioxolane ring (1). In the allose compound the coupling constant J,,, of 4.55 Hz may reflect freedom of rotation of the "tail" whereas in glucose the coupling constant, J,,, of 7.3 Hz, indicates a more preferred conformer.…”

Section: 2;56-di-0-isopropylidene-a-d-ribo-hexosesupporting

confidence: 55%

“…H systems (14). The presence of free hydroxyl in the gluco derivative (12) and in the ribo-hexofuranos-3-ulose gem diol (25) and the presence of a second possible hydrogen bond in the manno derivative (6) indicate the presence of alternate forces which may provide some rotameric preference to the "tail". That such forces are present is indicated by many of the J,,, couplings, the magnitude of which cannot possibly represent freely rotating systems.…”

Section: Acetyl and Keto Derivativesmentioning

confidence: 99%

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Conformational Studies on the 1,2;5,6-Di-O-isopropylidene-D-hexoses

Hall¹,

Black²,

Slessor³

et al. 1972

Can. J. Chem.

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Nuclear magnetic resonance studies on the 1,2;5,6-di-0-isopropylidene-D-hexofuranose sugars have provided information on the conformational preferences of the five-membered rings in these molecules. They appear to have strong conformational preferences rather than existing as freely pseudorotating systems. The furanose rings of the 3-deoxy-ribo and lyxo derivatives are found to preferentially exist in an envelope conformation in which C 4 is displaced from the plane of the ring. The arabino and xylo derivatives are found to be much less distorted, with preferred conformations approaching twist forms involving displacements of C-1 and -2. Substitution of various endo and exo groups at C-3 appears to have only minor influence on the parent furanose conformation.Les etudes r.m.n. sur les sucres de la serie des di-0-isopropylidine-1 ,2;5,6-D-hexofuranoses ont fourni des renseignements sur les conformations privilegites des cycles a cinq dans ces mol6cules. PlutBt que d'etre en pseudo-rotation libre, ces systemes apparaissent sous des conformations nettement prkfkrentielles. Les cycles furanoses des derives dtoxy-3 rib0 et Iyxo existent preferentiellement dans la conformation enveloppe dans laquelle le C 4 est au dehors du plan du cycle. Les derives arabino et xylo sont nettement moins tordus et adoptent la conformation privilkgik proche des formes "twist" impliquant les dkplacements des C-1 et -2. La substitution des divers groupes endo et exo sur le C-3 semble n'avoir qu'une influence mineure sur la conformation du furanose parent.

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Section: Acetyl and Keto Derivativessupporting

confidence: 58%

Section: 2;56-di-0-isopropylidene-a-d-ribo-hexosesupporting

confidence: 55%

Section: Acetyl and Keto Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Conformational Studies on the 1,2;5,6-Di-O-isopropylidene-D-hexoses

Hall¹,

Black²,

Slessor³

et al. 1972

Can. J. Chem.

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“…The deoxyfluoro-D-galactopyranose compounds were synthesized in these laboratories. 2-Deoxy-2-fluoro-Dgalactose (Adamson & Marcus, 1972), 3-deoxy-3fluoro-D-galactose (Brimacombe et al, 1970), 4-deoxy-4-fluoro-D-galactose (Marcus & Westwood, Vol. 139 1971) and 6-deoxy-6-fluoro-D-galactose (Taylor & Kent, 1958).…”

Section: Methodsmentioning

confidence: 99%

The use of deoxyfluoro-d-galactopyranoses in a study of yeast galactokinase specificity

Thomas

Bessell

Westwood

1974

Biochemical Journal

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1. 2-Deoxy-2-fluoro-d-galactose, 3-deoxy-3-fluoro-d-galactose, 4-deoxy-4-fluoro-d-galactose, 6-deoxy-6-fluoro-d-galactose and 2-deoxy-d-lyxo-hexose are substrates for yeast galactokinase. 2. The variation in K(m) values for the d-hexose derivatives was not associated with a variation in the value of K(m) for MgATP(2-) indicating that the binding of MgATP(2-) is not modified by the binding of the sugar substrate. 3. Donated H bonds from OH-3, OH-4 and OH-6 and an accepted H bond to OH-2 of the d-hexose are important for the binding of the sugar substrate to galactokinase. 4. Yeast galactokinase exhibits similar kinetics to the galactokinase from Escherichia coli and operates by a similar random sequential mechanism. 5. 4-Deoxy-4-fluoro-d-glucose was neither a substrate for nor an inhibitor of yeast galactokinase.

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“…Inversion of stereochemistry at the free OH and C4 was achieved by a three step process,36–39 oxidation to the corresponding ketone,40,41 conversion to the enol acetate and stereoselective reduction, presumably directed to the beta face by the bulky 1,2-α-acetonide. Selective cleavage of the acetate of 15 and fluorination with inversion gave 16 42.…”

mentioning

confidence: 99%

Synthesis and evaluation of 3″- and 4″-deoxy and -fluoro analogs of the immunostimulatory glycolipid, KRN7000

Raju

Castillo

Richardson

et al. 2009

Bioorganic & Medicinal Chemistry Letters

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Four 3"-and 4"-deoxy and -fluorogalactosyl ceramides were synthesized, and their ability to stimulate iNKT cells, based on levels of IL-2 production, was assessed in three NKT cell receptor hybridomas. In two of the hybridomas, 1.2 and 2H4, all of the analogs were immunostimulatory, while in the 1.4 hybridoma only the 4"-fluoro analog led to the production of significant levels of IL-2.Cluster of differentiation 1 (CD1) proteins are cell surface glycoproteins distantly related to the class I and II antigen presenting molecules of the major histocompatibility complex (MHC). 1 Unlike the MHC-encoded molecules, which bind and present peptide antigens, CD1 proteins bind a variety of lipids and present them to subsets of lipid-specific T cells. CD1d, a member of the CD1 family, has been shown to present lipid antigens to a specialized subset of lymphocytes known as invariant natural killer T (iNKT) cells. 2-7 Over the past decade CD1d activated iNKT cells have been demonstrated to elicit a range of immune responses with potential implications for treating viral and bacterial infections, cancer and a variety of autoimmune conditions. 8-14 Most studies of the role of iNKT cells have utilized the α-galactosyl ceramide (GalCer), KRN7000 (Figure 1), identified by Kirin Brewery in SAR studies centered around agelasphin-9b, a potent immunostimulatory compound isolated from the Agelus genus of marine sponge. 15 The activity of KRN7000 was found to be mediated by its binding to CD1d and subsequent activation of iNKT cells. 16 Because of the therapeutic potential of iNKT cell stimulation, there has been a growing interest in understanding how the glycolipid structure impacts the immune response. Thus, numerous α-glycosyl ceramides (α-GlyCers) have been synthesized and evaluated for their ability to stimulate iNKT cells.Using KRN7000 as a lead structure the majority of variations have been in the lipid portion. 17-23 Nevertheless, the carbohydrate moiety has been of interest 24-27 because it was assumed and later confirmed that it was this region of the antigen that protruded from the CD1d/ glycolipid complex and interacted with the iNKT T cell receptor (TCR). SAR studies had shown that the C2"-OH (for numbering see Figure 1) was essential for iNKT cell activation and that there was wide tolerance for functional group and size variations on C6". 24,27,28 In Supplementary data Supplementary data associated with this article (experimentals and characterization data) can be found, in the online version, at doi: .Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Autho...

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Fluorinated carbohydrates. Part VI. Studies of derivatives of 3-deoxy-3-fluoro-D-galactose

Cited by 33 publications

References 5 publications

Conformational Studies on the 1,2;5,6-Di-O-isopropylidene-D-hexoses

Conformational Studies on the 1,2;5,6-Di-O-isopropylidene-D-hexoses

The use of deoxyfluoro-d-galactopyranoses in a study of yeast galactokinase specificity

Synthesis and evaluation of 3″- and 4″-deoxy and -fluoro analogs of the immunostimulatory glycolipid, KRN7000

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