Reactivity Of Donors Research Articles

Multi-Component One-Pot Synthesis of the Tumor-Associated Carbohydrate Antigen Globo-H Based on Preactivation of Thioglycosyl Donors

Two efficient routes for the rapid assembly of the tumor-associated carbohydrate antigen Globo-H hexasaccharide 2 by a preactivation based iterative one-pot strategy are reported. The first method involves the sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47% overall yield in one-pot synthesis. Although model studies on constructing the challenging Gal-alpha-(1-4)-Gal linkage in Gb3 trisaccharide yielded the desired alpha linkage almost exclusively, a similar approach to assemble the hexasaccharide led to the formation of a significant amount of beta anomer. As an alternative, the second synthesis utilized three components in one pot with the Gal-alpha-(1-4)-Gal linkage preformed, producing the desired hexasaccharide in a similar overall yield as the four component approach. Both methods demonstrate that oligosaccharides containing alpha and beta linkages within the same molecule can be constructed in one pot via a preactivation based approach with higher glyco-assembly efficiencies than the automated solid-phase synthesis strategy. Furthermore, because glycosylations can be carried out independent of anomeric reactivities of donors, it is not necessary to differentiate anomeric reactivities of building blocks through extensive protective group adjustment for chemoselective glycosylation. This confers great flexibilities in the building block design, allowing matching of the donor with the acceptor, leading to improved overall yield.

Photo‐enhanced reactivation of Si donors deactivated by plasma‐induced defects in n‐type GaN

The behavior of plasma-induced defects deactivating Si donors in GaN has been studied by using Schottky diodes with the UV illumination. It is interesting that the UV irradiating for the deactivated GaN leads to an enhancement of reactivation of the donors even at room temperature. It is found that the donor-deactivated region in n-GaN shifts toward the bulk region with increasing the illumination time. The effect of the UV illumination is thought to be the direct photodissociation of the donor-defect complexes or the injection of holes as a minority carrier. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The use of 2- O-propagyloxycarbonyl protecting group in the selective formation of 1,2- trans-glycosidic linkage

The effect of N-phenylcarbamoyl (Car) and propagyloxycarbonyl (Poc) protecting groups at the O-2 position of donors was examined. The usefulness of Poc group in the selective formation of 1,2- trans-glycosidic linkage is shown by comparing the reactivity of donors having Car or acyl (Bz) groups.

Natural Hydrogen Donors in Petroleum Resids

A new method of measuring the donor hydrogen concentration and reactivity relative to tetralin was devised using dehydrogenation by 2−3-dichloro-5,6-dicyano-p-benzoquinone. Petroleum resids were found to contain high concentrations of natural hydrogen donors, and more are generated during thermolysis from substituted naphthenes in the resid. In contrast to the expected low concentration, the donor hydrogen concentration in the asphaltene fraction was found to be equivalent to the concentration in the full resid. However, the donor hydrogens in asphaltenes are more reactive than in any other fraction of the resid. This requires modifying the phase-separation mechanism for coke formation and the average chemical structure of asphaltenes. Thermal conversion of resid fractions in the presence of a super reactive hydrogen donor, 1,2,3,4-tetrahydroquinoline, showed that the selectivity to distillable liquids can be increased but the formation of polyaromatic cores cannot be prevented. In addition, reactive hydrogen donors greatly reduce the thermal reaction rate by reducing the free-radical concentration. On the basis of these and previous results, methods to increase visbreaker conversion and to inhibit thermal cracking are described and the concept of an economic optimum conversion in resid hydroconversion is proposed.

ABO-Incompatible Kidney Transplantation with and without Splenectomy

The letter to the editor from Dr. Mitsuhata et al. raises interesting points with regard to the role of splenectomy in ABO-incompatible (ABOI) kidney transplants. The authors contend that the classification of ABOI kidney transplant recipients as “high risk” should not be made on the basis of baseline antibody titer. The association of humoral rejection with baseline antidonor blood group antibody titer in splenectomized ABOI recipients not undergoing posttransplant plasmapheresis has been reported by Shimmura et al., who found a 70% humoral rejection rate in patients with baseline titer ≥128 and 20% in those with titers ≤1:64 (1). These findings are similar to those of our report in which rejection occurred in 12% of patients with titers <1:64, while 83% of those with titers exceeding 1:64 rejected (2). Interestingly, Shimmura et al. have recently reported that posttransplant plasmapheresis to maintain a low titer in conjunction with splenectomy is effective in preventing humoral rejection in ABOI recipients with very high baseline titers (3). In their letter, Mitsuhata et al. refer to their Brief Communication describing their use of mycophenolate mofetil during four weeks preceding ABOI transplantation in 18 patients compared to 18 patients who did not receive pretransplant mycophenolate mofetil (4). In their report, all patients underwent antibody lowering therapy with plasmapheresis or plasma exchange. No comment was made as to whether or not recipients underwent splenectomy, although their current letter to the editor implies that they did. They report improved allograft survival six months after transplant in the pretreated group, although the humoral rejection rate was comparable. The causes for allograft loss in the pretreatment group were not reported, nor were baseline antidonor blood group antibody titers. The authors indicate that on the day of transplantation antidonor blood group antibody titers ranging from 1–128, although not specifically reported. Given our admittedly smaller experience in ABOI kidney transplantation, we would be very reluctant to proceed to transplantation at the time the recipient's titer exceeded 1:16, and our practice is to continue to perform plasmapheresis until achieving a titer ≤1:8 on the day of transplantation. An important point is that the antibody titer depends strongly on the method used to measure it. It is possible that the antibody measurement technique used by Mitsuhata et al. differs from the technique reported in our investigation. The authors present their opinion that the benefits of transplantation without splenectomy are outweighed by the psychological, physical, and economic burden posed by posttransplant plasmapheresis and/or anti-CD20 antibody therapy. Our opinion is that with aggressive posttransplant antibody monitoring and therapy to maintain low titer during the first two weeks after transplantation, humoral rejection is an unusual complication in the large majority of ABOI kidney transplants. We also feel that the life long advantage of avoiding splenectomy exceeds the disadvantage of posttransplant therapy during the first one to two weeks after transplantation. Finally, the authors refer to the important fact that other potentially injurious antibodies with donor reactivity may also complicate ABOI transplantation, similar to ABO compatible transplants, and we agree. James Gloor Department of Internal Medicine and Nephrology Mayo Clinic Rochester, MN Mark Stegall Division of Transplantation Surgery Mayo Clinic Rochester, MN

Contrasting reactivity of thioglucoside and selenoglucoside donors towards promoters: implications for glycosylation stereocontrol

The stereochemical outcome of glycosylation reactions with model thioglycosides and selenoglycosides proved to be dependent on the source of promoter iodonium ion, with iodine giving different results to N-iodosuccinimide (NIS) alone or N-iodosuccinimide/trimethylsilyltrifluoromethanesulfonate (NIS/TMSOTf). In contrast to armed thioglycosides, which anomerise, and disarmed thioglycosides, which do not react, both armed and disarmed selenoglycosides give rise to the corresponding glycosyl iodides when reacted with iodine. Further, whilst the single electron transfer agent DDQ alone is an ineffective promoter, in combination with iodine it produces better acetonitrile-assisted β-stereoselectivity with both thioglycosides and selenoglycosides than does tris(4-bromophenyl)aminium hexachloroantimonate (BAHA).

Synthesis of Fluorinated Mucin Core 2 Branched Oligosaccharides with the Potential of Novel Substrates and Enzyme Inhibitors for Glycosyltransferases and Sulfotransferases

Syntheses of fluorinated mucin core 2 tri- and tetrasaccharides modified at the C-3 or C-4 position of the pertinent galactose residue are reported. These compounds were used for the study of sialyltransferases and 3-O-sulfotransferases involved in the biosynthesis of O-glycans. Our acceptor substrate specificity studies on three cloned sialyltransferases (Sia-Ts) revealed that a 3- or 4-fluoro substituent in beta1,4Gal resulted in poor acceptors for alpha2,6(N)Sia-T and alpha2,3(N)Sia-T, whereas 4-fluoro-Galbeta1,3GalNAcalpha was a good acceptor for alpha2,3(O)Sia-T. Uniquely, 4-F-Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-OBn was an inhibitor of alpha2,6(N)Sia-T activity but not alpha2,3(N)Sia-T activity. Further we found that the activities of only Gal 3-O-sulfotransferases and not sialyltransferases were adversely affected by a C-3 fluoro substituent at the other Gal terminal of mucin core 2. The strategy of building branched mucin core 2 structures by three glycosidation sequence coupling three classes of glycosyl donors with the reactivity-matching acceptors proved to be successful in syntheses of modified mucin-type core structures of O-glycan. The relative poor yields of the glycosylations using fluorinated galactosyl donors indicated that the fluorine modification dramatically decreased the donor reactivity due to electron-withdrawing effect.

Reactivity of neutral nitrogen donors in square-planar d 8 metal complexes: The system chloro(2,2′:6′,2″-terpyridine)platinum(II) cation with five-membered N-donor heterocycles in methanol

The kinetics of the forward and reverse steps of the reaction [Pt(terpy)Cl] + + nu ⇌ [Pt(terpy)(nu)] 2+ + Cl − (terpy = 2,2′:6′,2″-terpyridine, nu = one of a number of thiazoles, oxazole, isoxazole, imidazole, pyrazole and 3,5-dimethylpyrazole, covering a wide range of basicities) have been studied in methanol at 25 °C. Both forward and reverse reactions obey the usual two-term rate law observed in square-planar substitution. The second-order rate constants for the forward reactions, k 2 f , show a slight dependence upon the basicity of the entering nu, while the steric hindrance due to the presence of one methyl group in the α position to the nitrogen markedly decreases the reactivity. The second-order rate constants for the reverse reactions, k 2 r , are very sensitive to the nature of the leaving group and a plot of log k 2 r against the p K a of the conjugate acids of the unhindered five-membered N-donors is linear with a slope of −0.51. The results are compared with data from the literature regarding a series of pyridines reacting with the [Pt(terpy)Cl] + cation under the same experimental conditions. Both in the forward and in the reverse reaction, the reactivity depends not only upon the ligand basicity but also upon the nature of the nucleophile in the order: (thiazoles, oxazole, isoxazole, imidazole, pyrazoles) > pyridines for the entry of N-donors and on the contrary for the displacement by Cl −. Steric retardation, due to the presence of a methyl group in the α position to the nitrogen, is remarkably lower for five-membered N-donors if compared to pyridines both in the forward and in the reverse reaction.

Identification of Dialysis Patients with Panel-Reactive Memory T Cells before Kidney Transplantation Using an Allogeneic Cell Bank

Donor-reactive cellular sensitization does not routinely suggest humoral sensitization and vice versa, but both predict poor kidney transplant outcome. Irrespective of donor reactivity, panel-reactive antibody (PRA) screening identifies patients who are at enhanced risk. Therefore, it was hypothesized that panel-reactive memory T cell reactivity (PRT) might be an additional risk assessment factor of dialysis patients who are on the transplant waiting list. IFN-gamma-enzyme-linked immunosorbent spot memory T cell frequencies were determined in 10 healthy volunteers and 41 hemodialysis patients using for stimulation an allogeneic cell bank (ACB) from 17 healthy individuals who represented the most frequent white HLA antigens. Positive responses to ACB were analogous to PRA defined as percentage of positive assays of the ACB sets. Hemodialysis patients expressed higher PRT levels compared with healthy volunteers. Five of 10 PRT++ patients were PRA negative, and only four of 10 PRA++ patients exhibited PRT reactivity, suggesting independence of humoral and cellular sensitization. Pretransplantation PRT testing of recipients might improve individual risk assessment to make individualized therapy decisions.

Some Aspects of Selectivity in the Reaction of Glycosyl Donors.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Some Aspects of Selectivity in the Reaction of Glycosyl Donors*

Some advantages, disadvantages, and anomalies of various donors in glycosidations are discussed. By studying several two‐component donor/acceptor‐diol reactions, it is shown that regiopreferences are not very sensitive to the type of donor used. However, in competitive glycosidations within a given type of donor and between different types of donor, it is shown that regio‐ and chemoselectivities must be indexed to donor reactivity. * Dedicated to the memory of Professor Jacques van Boom.

Heterogeneity in Fetal Immunocompetence during the Second Trimester of Gestation

Objective: To address the role that alloreactivity may play and better define the window for histoincompatible stem cell transplantation in utero. Subjects, Material and Methods: We studied 9 fetal blood specimens obtained by cardiocentesis during elective abortions in the second trimester by multicolor flow cytometry and in vitro stimulation. Results: Lymphocytes ranged from adult levels (3/9) to >90% leukocytes. Six specimens had T cells within adult range. T cells in the other specimens were reduced, while B cells were conversely elevated. This variability did not correlate with gestational age, or leukocyte composition. Following 4 h of mitogenesis, fetal CD4+ and CD8+ T cells from 1 of 5 specimens showed a response similar to that of maternal T cells, while the other 4 specimens showed a diminished response (0.3 ± 0.2-fold). This heterogeneity did not correlate with gestational age, or lymphocyte subset distribution. Following 18 h of in vitro mitogenesis, fetal T cells from 2 specimens showed a response similar to that of maternal T cells (0.8 ± 0.2-fold). Despite that, one specimen gave a 3-fold greater response in a one-way mixed lymphocyte reaction vs. maternal cells compared to the other specimen. Conclusion: We determine that fetal immunocompetence differs greatly during the second trimester and assessment of host vs. donor reactivity prior to in utero transplantation is likely to potentiate more favorable outcomes.

Disarming, non-participating 2- O-protecting groups in manno- and rhamnopyranosylation: scope and limitations of sulfonates, vinylogous esters, phosphates, cyanates, and nitrates

A series of d-mannopyranosyl and l-rhamnopyranosyl thioglycosides protected with electron-withdrawing, non-participating protecting groups on O-2 have been prepared and investigated for their potential as β-glycosyl donors. Both α- and β-thioglycosides were investigated and the latter preferred on the grounds of enhanced stability at room temperature. A 2- O-nitro- l-rhamnosyl fluoride was also prepared and investigated. Moderate β-selectivities were observed with some of these donors. With the more powerfully electron-withdrawing groups reduced donor reactivity leads to a requirement for higher reaction temperatures and reduced selectivities. Decomposition temperatures of the intermediate glycosyl triflates were determined by variable temperature NMR spectroscopy and generally correlate with the disarming propensity of the protecting group system.

Iterative one-pot synthesis of oligosaccharides.

Straight to the point! Preactivation of a p-tolyl thioglycoside donor, followed by sequential addition of p-tolyl thioglycosyl acceptors in one reaction flask allowed rapid syntheses of oligosaccharides independent of anomeric reactivities of donors and acceptors (see scheme). This strategy greatly streamlines the assembly of oligosaccharides. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460176_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Preparation, properties, and applications of n-pentenyl arabinofuranosyl donors.

[reaction: see text] The development of n-pentenyl furanosyl donors has been tested using arabinose as a model. The readily prepared ortho ester (NPOE) is converted into disarmed (NPG(AC)) and thence armed (NPG(ALK)) n-pentenyl arabinofuranosides. The reactivities of these furanosyl donors and pyranosyl counterparts have been assessed by allowing pairs of both to compete for an acceptor. For the NPOE and armed (NPG(ALK)) pairs, coupling products were obtained from donors, whereas for the disarmed (NPG(AC)) pair, only the arabinofurano coupled product was obtained. To probe their synthetic utility, the NPOE was shown to be the only precursor needed to prepare an alpha-1,5-linked arabinan segment of the complex lipoarabinomannan cell wall array of Mycobacterium tuberculosis.

Synthesis and reactivity of amino-substituted BEDT-TTF donors as building blocks for bifunctional materials

The first two amino-substituted BEDT-TTF derivatives, aminomethyl-ET (AMET) and aminoethyl-ET (AEET), have been prepared; the critical step in both cases was a hetero Diels–Alder reaction with 1,3-dithiole-2,4,5-trithione. AEET shows expected reactivity towards electrophiles whereas AMET will not react with aryl acid chlorides or sulfonyl chlorides, but amides of AMET can be produced by DCC coupling and mixed anhydride methods.

The C‐4 Configuration as a Probe for the Study of Glycosidation Reactions

AbstractThe difference in the electron‐withdrawing powers of axial and equatorial OBn was used as a probe to investigate the glycosidation reaction. The reactivity of perbenzylated glucosyl and galactosyl donors were compared under a range of glycosidation conditions that involved variations in catalyst, solvent, and glycosyl acceptor. Generally, the galactosyl donor had a reactivity four to five times higher than the glucosyl donor, which is in accord with the transition state having positive character. In certain cases, however, particularly when triflate was present, equal reactivity of glucosyl and galactosyl donors were found. The results are explained in terms of changes in the rate‐determining steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)

Intragraft gene and protein expression in rat liver allografts treated with costimulatory blockade alone or in combination with CyA

Background. Costimulatory blockade has been shown to prevent acute rejection (AR) and promote long-term graft survival in a number of animal models including nonhuman primates. The effect of concomitant administration of conventional immunosuppressives on long-term liver allograft survival and intragraft expression of immune mediators has not previously been examined. Materials and methods. A high-responding Dark Agouti to Lewis orthotopic liver transplant (LEW OLT) model was used to compare anti-CD154 alone, or in combination with cyclosporin (CyA) on allograft survival. Donor-specific reactivity was assessed by mixed lymphocyte reaction (MLR) and allogeneic skin grafts. Surviving rats were euthanized on day 150 and intragraft gene (CD80, 86, 152, 154, IFN-γ, IL-2, IL-6, IL-10, IL-13, TNF-α, TGF-β, IL-7, Fas-ligand, Granzyme B, bax, and bcl 2) and protein (CD4, CD8, ED1, CD154, CD80, CD86) expression was measured. Results. Untreated control recipients had a median survival time of 5 days. Recipients treated with anti-CD154 survived to beyond 150 days with no evidence of AR. Concomitant administration of CyA did not alter the long-term survival. There was no difference in the serum aspartate aminotransferase between treatment groups or a change over time. All treated recipients showed a reduction in donor-specific MLR at day 40 and 60 but had persistence of donor reactivity to skin grafts at day 100. Histologically, liver architecture was well preserved despite the presence of a nondestructive mononuclear cell infiltrate. Analysis of intragraft gene expression revealed an inverse relationship between the duration of anti-CD154 therapy and the gene expression of costimulatory molecules and Th1 cytokine transcripts. The pro-apoptotic gene, bax, was increased in recipients treated with anti-CD154, but not CyA, compared with normal liver. Conclusions. These data demonstrate that anti-CD154 therapy either alone or in combination with CyA allows for the long-term survival of liver allografts in the rat despite there being a difference in the intragraft gene and protein profile.

A mild and convenient indium(III) chloride-catalyzed synthesis of thioglycosides

The efficiency of glycosidation reactions generally involves a high chemical yield, as well as high/complete stereo- and regioselectivity. All these depend on the compatibility of the reactivity of glycosyl donors and acceptors. Among glycosyl donors, thioglycosides are widely used because of their high degree of stability in many organic reactions. Although there are number of methods available for the preparation of thioglycosides, all of them have one or more disadvantages, especially concerning the time factor and cumbersome workup procedures. Here we report a convenient and high-yielding method for the preparation of thioglycosides.

Linear Synthesis of the Tumor‐Associated Carbohydrate Antigens Globo‐H, SSEA‐3, and Gb3.

The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were synthesized in a linear fashion using glycosyl phosphate monosaccharide building blocks. All of the building blocks were prepared from readily available common precursors. The difficult α-(1→4-cis)-galactosidic linkage was installed using a galactosyl phosphate donor with high selectivity. Introduction of the β-galactosamine unit required the screening a variety of amine protecting groups to ensure good donor reactivity and protecting group compatibility. An N-trichloroacetyl-protected galactosamine donor performed best for the installation of the β-glycosidic linkage. Conversion of the trichloroacetyl group to the N-acetyl group was achieved under mild conditions, fully compatible with the presence of multiple glycosidic bonds. This synthetic strategy is expected to be amenable to the synthesis of the globo-series of tumor antigens on solid-support.