Synthesis of L-daunosamine and L-ristosamine glycosides via photoinduced aziridination. Conversion to thioglycosides for use in glycosylation reactions

Application of photoinduced acylnitrene aziridination to the syntheses of L-daunosamine and L-ristosamine glycosides is reported. Photoreaction of methyl 4-O-azidocarbonyl-2,3,6-trideoxy-L-hex-2-enopyranosides, followed by aziridine opening, leads to 3-amino-3-N-,4-O-carbonyl-2,3,6-trideoxy precursors to the aminosugar methyl glycosides. Conversion of these precursors to their thioglycoside analogues followed by N-acetylation of the carbamate moiety permits high yielding and, in some cases, stereoselective glycosylations using the 1-benzenesulfinylpiperidine-triflic anhydride activation method developed by Crich and co-workers. Glycosylations involving activation with N-iodosuccinimide and silver triflate were also successful, but the stereoselectivities of these reactions in general were lower.     

Subtle stereochemical and electronic effects in iridium-catalyzed isomerization of C-allyl glycosides

[reaction: see text] Stereoselective isomerization of C-allyl glycosides into (E)-C-vinyl glycosides or (Z)-exo-glycals was carried out in the presence of the cationic iridium(I) catalyst [(Ph(2)MeP)(2)Ir(cod)PF(6)]. The products of the isomerization were affected by the relative 1,2-stereochemical relationships and by the nature of the protecting groups. These effects are discussed along with a plausible reaction mechanism.     

Practical synthesis of latent disarmed S-2-(2-propylthio)benzyl glycosides for interrupted Pummerer reaction mediated glycosylation

Practical synthetic methods to latent disarmed S-2-(2-propylthio)benzyl (SPTB) glycosides for interrupted Pummerer reaction mediated glycosylation have been discovered. Among them, both coupling reaction of PTB-Cl with glycosyl thiols and BF₃·OEt₂ promoted reaction of peracylated glycosides with PTB-SH produced peracylated SPTB glycosides in large scales and with high efficiency.     

Interrupted Pummerer Reaction in Latent‐Active Glycosylation: Glycosyl Donors with a Recyclable and Regenerative Leaving Group

Latent O‐glycosides, 2‐(2‐propylthiol)benzyl (PTB) glycosides, were converted into the corresponding active glycosyl donors, 2‐(2‐propylsulfinyl)benzyl (PSB) glycosides, by a simple and efficient oxidation. Treatment of the PSB donor and various acceptors with triflic anhydride provided the desired glycosides in good to excellent yields. The leaving group, which was activated by an interrupted Pummerer reaction, can be recycled (PSB‐OH) and regenerated as the precursor (PTB‐OH). A natural hepatoprotective glycoside, leonoside F, was efficiently synthesized in a convergent [3+1] manner with this newly developed method. The present total synthesis also led to a structural revision of this phenylethanoid glycoside.     

Synthesis and evaluation of antiviral activity of L-acosamine and L-ristosamine nucleosides of furanose configuration.

Mercuric-catalyzed hydrolysis of acetylated L-rhamnal 1 gives an alpha,beta-unsaturated aldehyde 2. 1,4-Addition of DBU-phthalimide salt with concomitant acetyl shift resulted in L-ribo and L-arabino isomers of 5-O-acetyl-2,3,6-trideoxy-3-phthalimido-hexofuranose 3 and 4. After acetylation at the anomeric center, coupling with silylated thymine resulted in three new nucleosides, with L-acosamine and L-ristosamine of furanose configuration as the carbohydrate moiety. The target compounds have been evaluated for their antiviral activity against HIV and HSV-1.     

Thermal decomposition of anomeric glycopyranosides

Thermal analysis studies coupled with chemical studies indicate that glycopyranosides undergo thermal decomposition in two overlapping stages. The initial reaction of the glycosides at temperature between 200 and 300°C is cleavage and volatilization of the glycosidic group as the corresponding alcohol, followed by intra- or inter-molecular condensation of the glycosyl portion of the molecule. At higher temperatures (310–340°C) the major reaction is fragmentation of the carbohydrate into a variety of low molecular-weight compounds. Studies with a series of anomeric methyl and phenyl glycosides indicate that, with the methyl and phenyl glycosides, the rate of the low-temperature condensation reaction was dependent on anomeric configuration of the starting glycoside.     

Synthesis of silylallene glycosides and diene diglycosides by C-glycosidation of D-glucal with 1,4-bis(trimethylsilyl)-2-butyne

[reaction: see text] Silylmethylallenyl glycosides, symmetrical and unsymmetrical diene glycosides, were synthesized by C-glycosidation with 1,4-bis(trimethylsilyl)-2-butyne in good yield. The nature of the product is controlled by the choice of Lewis acid, BF(3).OEt(2), or SnCl(4). The efficient construction of unsymmetrical diene glycosides was achieved in one pot on the basis of the order of addition of sugar starting materials.     

1-O-vinyl glycosides via Tebbe olefination, their use as chiral auxiliaries and monomers

A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding 1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as anomerically pure compounds in good yields, and the method of preparation was compatible with the presence of a variety of functional groups. Remarkably, the anomeric formate group was regioselectively converted into the corresponding olefin in the presence of acetate and benzoate protecting groups. With the perspective to use the 1-O-vinyl glycosides as monomers for the preparation of glycosylated poly(vinyl alcohol) derivatives with controlled tacticity, their scope as chiral auxiliaries for a stereodifferentiation in addition reactions to the olefin function was investigated by using the [2+2] cycloaddition to dichloroketene as a model reaction. In particular, vinyl 2,3,4,6-tetra-O-benzoyl-alpha-d-mannopyranoside (2i) exhibited excellent diastereoselectivity. Finally, the 1-O-vinyl glycosides were successfully subjected to radical homopolymerization in bulk or used as electron-rich comonomers in radical copolymerizations with maleic anhydride, yielding alternating, glycosylated poly(vinyl alcohol-alt-maleic anhydride).     

Copper-mediated O-arylation of lactols with aryl boronic acids

A novel and efficient method to access phenolic glycosides has been established by using copper-mediated coupling reaction of aryl boronic acids with hemiacetals. The reaction enjoyed a wide range of substrate scope, and many phenolic glycosides can be synthesized in good yields.     

Vinyl Glycosides in Oligosaccharide Synthesis. 2. The Use of Allyl and Vinyl Glycosides in Oligosaccharide Synthesis

A novel latent-active glycosylation strategy has been described that relies on the isomerization of substituted allyl glycosides to give the corresponding vinyl glycosides, which can subsequently be used in Lewis acid-mediated glycosylations. The isomerization reaction was performed by a rhodium catalyst obtained by treating tris(triphenylphosphine)rhodium(I) chloride with n-butyllithium. This catalyst has many advantageous properties over the use of conventional Wilkinson's catalyst. The glycosylation reactions gave high yields for both primary and secondary sugar alcohols, and the anomeric selectivity could be controlled by the constitution of the glycosyl donor and reaction conditions. The new isomerization and glycosylation approach enables complex oligosaccharides of biological importance to be prepared in a highly convergent manner.     

Total synthesis of everninomicin 13,384-1--Part 4: explorations of methodology; stereocontrolled synthesis of 1,1'-disaccharides, 1,2-seleno migrations in carbohydrates, and solution- and solid-phase synthesis of 2-deoxy glycosides and orthoesters

Methods for the stereocontrolled construction of 1,1'-disaccharides, 2-deoxy glycosides, and orthoesters are reported. Specifically, a tin-acetal moiety was utilized to fix the anomeric stereochemistry of a carbohydrate acceptor leading to an efficient and stereoselective synthesis of 1,1'-disaccharides, while a newly discovered 1,2-phenylseleno migration reaction in carbohydrates opened entries to 2-deoxy glycosides and orthoesters. Thus, reaction of 2-hydroxy phenylselenoglycosides with DAST led to 2-phenylselenoglycosyl fluorides which reacted with carbohydrate acceptors to afford, stereoselectively, 2-phenylselenoglycosides. The latter compounds could be reductively deselenated to 2-deoxy glycosides or oxidatively converted to orthoesters via the corresponding ketene acetals.     

Diastereoselective Ni-catalyzed Negishi cross-coupling approach to saturated, fully oxygenated C-alkyl and C-aryl glycosides

A Ni-catalyzed Negishi cross-coupling approach to C-glycosides is described with an emphasis on C-aryl glycosides. The combination of NiCl2/PyBox in N,N'-dimethylimidazolidinone (DMI) enabled the synthesis of C-alkyl glycosides under mild reaction conditions. Moderate yields and beta-selectivities were obtained for C-glucosides, and good yields and high alpha-selectivities were the norm for C-mannosides. For C-aryl glycosides, reactions employing Ni(COD)2/(t)Bu-Terpy in N,N-dimethylformamide (DMF) were typically high yielding and provided C-glucosides with high beta-selectivities (1:>10 alpha:beta) and C-mannosides in moderate alpha-selectivities (3:1 alpha:beta); alpha-C-aryl glycosides could be obtained by the combination of Ni(COD)2/PyBox in DMF (>20:1 alpha:beta). The collective studies suggest that stereochemical control of the C-glycosides is dependent on the substrate and catalysts combination. The Negishi protocol displays excellent functional group tolerance, as demonstrated by its use in the first total synthesis of the natural product salmochelin SX.     

Simple and mild stereoselective O-glycosidation using 1,2-anhydrosugars under neutral conditions

The ring opening of α-d-1,2-anhydrohexapyranoses with phenols proceeded smoothly in ethyl acetate (neutral conditions) in the absence of metal ion catalysts or additives to stereoselectively furnish 1,2-cis-α-aryl glycosides as the major product and 1,2-trans-β-aryl glycosides as the minor product in good yields. Under similar conditions, this ring opening reaction with alcohols afforded exclusively β-alkyl glycosides in excellent yields.     

Rapid quantification of iridoid glycosides analogues in the formulated Chinese medicine Longdan Xiegan Decoction using high-performance liquid chromatography coupled with mass spectrometry [corrected

Longdan Xiegan Decoction (LXD) is a formulated preparation composed of 10 ingredient herbs, with iridoids as the main bioactive components. In this study, a rapid, simple and reliable method of simultaneous determination of four iridoid glycosides in LXD using high-performance liquid chromatography (HPLC) coupled with electrospray ionization mass spectrometry (MS) was first developed and validated. The four iridoid glycosides references were isolated from LXD extract and purified using a preparative HPLC chromatography. The sample preparation for quantification comprised of a simple ultrasonic extraction and the satisfactory chromatographic separation of the four structurally similar iridoid glycosides was effected in less than three minutes on a CAPCELL PAK C(18) MGII column (3 microm, 100 mm x 2.0 mm), using an elution system of 10% methanol and their concentrations in different batches of LXD and ingredient herbs were simultaneously determined by HPLC-MS/MS using a multiple reaction monitoring (MRM) mode. The method was validated with respect to the overall intra- and inter-day variation (RSD less than 8%) and the limits of quantification for the four iridoid glycosides were 35, 20, 37 and 33 ng/mL, respectively.     

S-Benzoxazolyl (SBox) glycosides as novel,versatile glycosyl donors for stereoselective 1,2-cis glycosylation

[reaction: see text] Novel glycosyl donors, S-benzoxazolyl (SBox) glycosides, have been synthesized, tested toward various protecting group manipulations, and applied to the highly stereoselective 1,2-cis glycosylation. These compounds fulfill the requirements for a modern glycosyl donor such as accessibility, high stability toward protecting group manipulations, and mild activation conditions. It was also demonstrated that SBox glycosides withstand other glycosyl donor activation conditions and therefore allow selective glycosylations of O-pentenyl and thioglycosides.     

A new versatile strategy for C-aryl glycosides

A versatile strategy involving a sequential intermolecular enyne metathesis of C-alkynyl glycosides with ethylene, Diels-Alder, and aromatization reactions is successfully developed to provide a range of C-aryl glycosides. [reaction: see text]     

Domino meta-C−H Ethyl Glycosylation by Ruthenium(II/III) Catalysis: Modular Assembly of meta-C-Alkyl Glycosides

Glycosyl anomeric radical addition reactions have been well-explored and proved efficient for the C-alkyl glycosides synthesis, but multicomponent Domino transformations for the rapid and controllable construction of structurally diversified C-alkyl glycosides in a single step are still rare. In contrast, we, herein, report a ruthenium(II)-catalyzed Domino meta-C−H ethyl glycosylation, enabling the construction of challenging meta-C-alkyl glycosides. Our ruthenium(II) catalysis was reflected by the mild reaction condition, exclusive meta-site selectivity and high levels of anomeric selectivity. In addition, the ruthenium(II)-catalyzed Domino meta-C−H glycosylation allowed for the synthesis of versatile 1,2-trans-C-alkyl glycosides with commercially available vinyl arenes, acrylates and easily accessible glycosyl bromides.     

Expanding the application scope of glycosidases using click chemistry

Glycosidase-mediated glycosylation of alkynyl alcohols and azide-containing alcohols was followed by a click reaction, affording various types of triazole glycosides. The activities of triazole glycosides detected in subsequent bioassays show that this procedure is a feasible approach to the development of anti-fungal drugs.     

Synthesis of 2-deoxy-2-c-alkyl glycal and glycopyranosides from 2-hydroxy glycal ester

A method to convert 2-hydroxy glycal ester to the corresponding 2-deoxy-2-C-alkyl glycal in a facile manner, through key reactions including (i) C-allylation at C-1, (ii) Wittig reaction, and (iii) Cope rearrangement of a 1,5-diene derivative, is reported. The α-anomer of the 1,5-diene derivative underwent Cope rearrangement to afford 2-deoxy-2-C-glycal derivative, whereas the β-anomer was found to be unreactive. Employing this sequence, 3,4,6-tri-O-benzyl-2-O-acetyl-1,5-anhydro-d-arabino-hex-1-enitol was transformed to 3,4,6-tri-O-benzyl-2-deoxy-2-C-alkyl-1,5-anhydro-D-arabino-hex-1-enitol. 2-Deoxy-2-C-alkyl glycal derivative is a suitable glycosyl donor to prepare 2-deoxy-2-C-alkyl glycosides, mediated through haloglycosylation and a subsequent dehalogenation. A number of 2-deoxy-2-C-alkyl glycosides, with both glycosyl and nonglycosyl moieties at the reducing end, are thus prepared from the glycal.