Synthesis of a Sialic Acid Dimer Derivative, 2‘α-<i>O</i>-Benzyl Neu5Ac-α-(2→5)Neu5Gc

The preparation of a disaccharide 2, Neu5Ac-α-(2→5)Neu5Gc having a α-benzyl protecting group at the reducing end, by the coupling of the easily accessible building units 4 and 5 is described. Subsequent deprotection of the coupling adduct led to the isolation of the target compound 2 in high yield

2-C<i>-</i>Branched Glycosides from 2‘-Carbonylalkyl 2-<i>O-</i>Ms(Ts)-<i>C-</i>Glycosides. A Tandem S_N2−S_N2 Reaction via 1,2-Cyclopropanated Sugars

Under basic conditions, 2‘-aldehydo (acetonyl) 2-O-Ms(Ts)-α-C-glycosides undergo an intramolecular SN2 reaction to form 1,2-cyclopropanated sugars, which react with nucleophiles (alcohols, thiols, and azide) at the anomeric carbon to give 2-C-branched glycosides. By way of contrast, the 1,2-cyclopropanes derived from 2‘-ketones only react with thiols to give 2-C-branched thioglycosides

Polyhydroxylated Indolines and Oxindoles from <i>C</i>-Glycosides via Sequential Henry Reaction, Michael Addition, and Reductive Amination/Amidation

6-Nitro-2‘-carbonyl-C-glycofuranosides synthesized via Henry reaction from 1-C-allyl 5-aldo-C-glycoside underwent an intramolecular Michael addition to afford nitrocyclohexanol derivatives in good to excellent yield. Reduction of the nitro group followed by intramolecular amination with ketone and aldehyde and amidation with ester produced indoline and oxindole derivatives, respectively, in excellent yield

Properties of Astaxanthin/Ca²⁺ Complex Formation in the Deceleration of Cis/Trans Isomerization

Deceleration of the regioselective cis/trans isomerization of all-trans-astaxanthin (ASTX) in the presence of Ca2+ was shown by HPLC analysis. The NMR and ITC analyses provided evidence for complexation of ASTX with Ca2+ in 1:2 stoichiometry via chelation at both carbonyl and hydroxyl groups. The rotation across torsion ω6 (C5−C6−C7−C8) upon complexation is consistent with the NOE between 7-H and 5-CH3. This study supports the inhibitory effect of ASTX on calcium-induced turbidity of lens crystallins

Synthesis of a Tetrasaccharide Glycosyl Glycerol. Precursor to Glycolipids of <i>Meiothermus taiwanensis</i> ATCC BAA-400

Synthesis of a tetrasaccharide glycosyl glycerol, the core structure of glycoglycerolipid from Meiothermus taiwanensis ATCC BAA-400, was described. A one-pot glycosylation with three components was employed as a key step

1,2-Migration of 2‘-Oxoalkyl Group and Concomitant Synthesis of 2-<i>C</i>-Branched <i>O</i>-, <i>S</i>-Glycosides and Glycosyl Azides via 1,2-Cyclopropanated Sugars

Treatment of 2‘-oxoalkyl 2-O-Ms(Ts)-α-C-mannosides (4, 5, and 6) with base resulted in 1,2-cyclopropanation via an intramolecular SN2 reaction due to their 1,2-trans-diaxial configurations. The 1,2-cyclopropanated sugars (10 and 13) were reacted with various alcohols, thiols, and sodium azide to produce 2-C-branched O- and S-glycosides and glycosyl azides (11, 14−28) in good to excellent yields. In contrast, 1,2-cis 2‘-oxoalkyl 2-O-Ms(Ts)-α-C-glucoside 9 formed an acyclic conjugated aldehyde (31) under basic conditions, which occurred by 1‘-enolation followed by β-elimination. An intramolecular Michael addition from 31 produced 2-O-Ms-β-C-glucoside 30 as a major product. However, due to the electron-withdrawing effect exerted by 2-O-Ms compound 31 also undergoes a C2 epimerization to form 32. Thereafter, the intramolecular Michael addition led to the formation of both 1,2-trans 2‘-oxoalkyl 2-O-Ms-α-C-mannoside 4 and its β-anomer (33). Because β-elimination/Michael addition and C2 epimerization are reversible reactions, equilibriums among 9, 31, 30, 32, 33, and 4 were established, which included the transformation of 1,2-cis C-glucoside 9 into 1,2-trans C-mannoside 4. The subsequent 1,2-cyclopropanation of 4 was an irreversible reaction yielding 1,2-cyclopropanated 10 and further conversion to 1,2-migration products (11 and 12)

Novel Zinc (II)-Mediated Epimerization of 2‘-Carbonylalkyl-α-<i>C</i>-glycopyranosides to Their β-Anomers

2‘-Aldehydes and 2‘-ketones of α-C-glycosides, including the gluco-, galacto-, and manno- series, were epimerized exclusively to their β-anomers in good-to-excellent yields under basic conditions and in the presence of zinc acetate. The β-stereoselectivity is independent of the neighboring group at 2-O-substitution of sugar substrates. Therefore, this provides a particularly useful method for the preparation of manno-β-C-glycosides. The epimerization is likely initiated by the formation of Zn-enolate that is stabilized by intramolecular chelation to the pyranose ring-oxygen to form a syn chair-boat structure. Due to the activation generated by the Zn−O coordination, fission of the C1−O bond occurs, leading to opening of the pyranose ring, which is spontaneously followed by a change in conformation. The more stable anti chair-boat transition state is favored, and the subsequent hetero-intramolecular Michael addition results in the formation of β-C-glycoside in a ring-closure step

Epimerization of 2‘-Carbonylalkyl-<i>C</i>-Glycosides via Enolation, β-Elimination and Intramolecular Cycloaddition

Treatment of 2‘-carbonyl-α-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars with 4% NaOMe resulted in anomeric epimerization to give their respective β-anomers in good to excellent yields. The epimerization of the 2‘-aldehyde of α-C-galactopyranoside (10) in deuterium methanol, which afforded the β-anomer with exclusive deuterium replacements at the 1‘-position, excluded the possibility of the exo-glycal as being involved as an intermediate. When 2‘-aldehyde (36) and 2‘-ketone (41) of 2,3-di-O-benzyl-α/β-l-C-arabinofuranoside were used as substrates we were able to obtain the respective equatorial α-C-arabinopyranosides (37 and 42). These observations confirmed that the epimerization involves an acyclic α,β-unsaturated aldehyde or ketone, which is formed by the enolation of 2‘-carbonyl-α-C-glycoside with subsequent β-elimination. Thereafter an intramolecular hetero-Michael cycloaddition occurs, leading to the formation of thermodynamically controlled stable products, which were exclusively the equatorial C-glycopyranosides, except in the case of 2‘-carbonyl-C-furanosides, where a mixture of two anomers was obtained

Epimerization of 2‘-Carbonylalkyl-<i>C</i>-Glycosides via Enolation, β-Elimination and Intramolecular Cycloaddition

Treatment of 2‘-carbonyl-α-C-glycopyranosides of gluco, galacto, manno, 2-deoxy, and 2-azido sugars with 4% NaOMe resulted in anomeric epimerization to give their respective β-anomers in good to excellent yields. The epimerization of the 2‘-aldehyde of α-C-galactopyranoside (10) in deuterium methanol, which afforded the β-anomer with exclusive deuterium replacements at the 1‘-position, excluded the possibility of the exo-glycal as being involved as an intermediate. When 2‘-aldehyde (36) and 2‘-ketone (41) of 2,3-di-O-benzyl-α/β-l-C-arabinofuranoside were used as substrates we were able to obtain the respective equatorial α-C-arabinopyranosides (37 and 42). These observations confirmed that the epimerization involves an acyclic α,β-unsaturated aldehyde or ketone, which is formed by the enolation of 2‘-carbonyl-α-C-glycoside with subsequent β-elimination. Thereafter an intramolecular hetero-Michael cycloaddition occurs, leading to the formation of thermodynamically controlled stable products, which were exclusively the equatorial C-glycopyranosides, except in the case of 2‘-carbonyl-C-furanosides, where a mixture of two anomers was obtained

Astaxanthin Interacts with Selenite and Attenuates Selenite-Induced Cataractogenesis

Selenite, the most commonly encountered toxic form of selenium, in overdose, is used to induce cataracts in rats. This study demonstrated that selenite, but not selenate, would interact with the carotenoid astaxanthin (ASTX), as determined using isothermal titration calorimetry and NMR. The maximum absorption of ASTX decreased with increasing selenite concentration, indicating that the conjugated system of ASTX was changed by selenite. Such interactions between ASTX and selenite were also supported by the attenuation of selenite-induced turbidity by ASTX (0−12.5 μM) in vitro. In vivo experiments also showed that ASTX attenuated selenite-induced cataractogenesis in rats. In summary, this is the first report of a direct interaction of ASTX with selenite. This interaction is supported by an in vitro assay and may be partially responsible for the ASTX observed in vivo protection against selenite-induced cataractogenesis