Glycosyl Derivatives Research Articles

Thioureido-β-cyclodextrins as molecular carriers

Alkyl, glycosyl and glycopeptidyl derivatives of 6I-deoxy-6I-thioureidocyclomaltoheptaose, prepared in high yield from either 6I-amino-6I-deoxycyclomaltoheptaose or the corresponding 6I-isothiocyanate, exhibit considerably enhanced water solubilities as compared with the native β-cyclodextrin.

Synthesis of glycosylated hydroxyproline building blocks

The synthesis of a series of new glycosylated N α-Fmoc hydroxyproline building blocks has been accomplished for the first time with two approaches. First, by glycosylation of N α-Fmoc Hyp OH, having unprotected carboxyl group with different peracetylated glycosyl derivatives. Alternatively, by glycosylation of its derivative N α-Fmoc Hyp Opfp with different acylated glycosyl derivatives under silver triflate promotion. The use of benzoyl groups instead of acetyl as protecting groups for the carbohydrate moiety boosted the yield of glycosidation of N α-Fmoc Hyp Opfp. These building blocks are ready for their incorporation into solid-phase glycopeptide synthesis protocols.

Sugar Calixarenes: Preparation of Calix[4]arenes Substituted at the Lower and Upper Rims with O‐Glycosyl Groups

A chiral hydrophilic environment is created at either rim of calix[4]arene by the synthesis of glycosyl derivatives such as the water-soluble tetragalactosyl calixarene 1. This derivative is potentially an attractive synthetic receptor for chiral recognition of polar organic molecules.

Recognition of purine bases and nucleosides by the amino acid carboxylic group

Interactions of adenosine, guanosine and some of their methyl derivatives, as well as hypoxanthine, xanthine and a number of their methyl and glycosyl derivatives with neutral and ionized forms of the carboxylic group in anhydrous DMSO, have been investigated by UV, IR and PMR spectroscopy. A consideration of our data and the results of other authors showed that the ionized carboxylic group specifically interacts with each of the unmethylated purine bases of the nucleosides. Monomethylation of adenosine and guanosine amino groups does not change the nature of their interactions with the carboxylate ion. Methylation of guanosine and inosine at the N1 positions makes them unable to interact with both forms of the carboxylic group, but imparts the ability to interact with the neutral carboxylic group through a proton transfer to adenosine. Inosine and guanosine methylated at the N7 positions become able to form complexes with the neutral carboxylic group through a proton transfer as well. Xanthosine and inosine methylated at the N7 atoms form weak complexes with the carboxylate ion involving C8H protons. Analysis of the data obtained and results of previous work provides spectroscopic evidence for the ability of the amino acid carboxylic group to differentiate between all the purine bases and most of their methyl derivatives.

Взаємодія метил- та глікозилпохідних піримідинових нуклеотидних основ з карбоксильною групою амінокислот

Взаємодія метил- та глікозилпохідних піримідинових нуклеотидних основ з карбоксильною групою амінокислот

Synthesis of new aminocyclitols as potent enzymatic inhibitors

The syntheses of new pseudo-saccharides having an allylic amino moiety or an aziridine group are reported starting from methyl-α-D-glucopyranoside. To enhance the hydrophilic / lipophilic balance, pseudo-saccharides 9 and 10 were linked with a glycosyl derivative.

The deficiency of sterol biosynthesis in Saccharomyces cerevisiae affects the synthesis of glycosyl derivatives of dolichyl phosphates

Mutants deficient in sterol (thermosensitive ergosterol auxotrophs) erg 8, 9, 12 and heme synthesis hem 1, 12 were screened for the level of free dolichol and dolichyl phosphate synthesized in the mevalonate pathway as well as for the activity of dolichyl phosphate-dependent glycosyl transferases. The amount of DolP synthesized via CTP-dependent phosphorylation was the same in mutants and parental strains. However, mannosylation and glucosylation of endogenous dolichyl phosphates in ergosterol mutants was about four times lower compared to parental strains, while the same reactions carried out with exogenous Dol24P reached 80% of the level observed in parental strains indicating that activities of DolPMan and DolPGlc synthases are not the rate-limiting factors. It is postulated that the de novo synthesis of DolP is impaired in the ergosterol mutants. Moreover, a block in the ergosterol branch of the metabolic pathway (erg 9) causes an increase in the de novo synthesis of dolichyl phosphate.

The deficiency of sterol biosynthesis in Saccharomyces cerevisiae affects the synthesis of glycosyl derivatives of dolichyl phosphates.

Mutants deficient in sterol (thermosensitive ergosterol auxotrophs) erg 8, 9, 12 and heme synthesis hem 1, 12 were screened for the level of free dolichol and dolichyl phosphate synthesized in the mevalonate pathway as well as for the activity of dolichyl phosphate-dependent glycosyl transferases. The amount of DolP synthesized via CTP-dependent phosphorylation was the same in mutants and parental strains. However, mannosylation and glucosylation of endogenous dolichyl phosphates in ergosterol mutants was about four times lower compared to parental strains, while the same reactions carried out with exogenous Dol24P reached 80% of the level observed in parental strains indicating that activities of DolPMan and DolPGlc synthases are not the rate-limiting factors. It is postulated that the de novo synthesis of DolP is impaired in the ergosterol mutants. Moreover, a block in the ergosterol branch of the metabolic pathway (erg 9) causes an increase in the de novo synthesis of dolichyl phosphate.

Исследование взаимодействия гипоксантина, ксантина и их метил- и гликозилпроизводных с карбоксильной группой аминокислот спектроскопическими методами

Исследование взаимодействия гипоксантина, ксантина и их метил- и гликозилпроизводных с карбоксильной группой аминокислот спектроскопическими методами

Vectorised transport of drugs: Synthesis of a new glycosyl derivative of β-cyclodextrin.

Monosubstitution at the O-6 position of β-cyclodextrin by a β-N-glucosyl residue has been achieved with a spacer C 9 diamide as the interglycosidic linkage. The new glycosyl derivative has been characterised by 1H N.M.R. (COSY-RCT), is much more soluble (200g.1 −1) in water and has been shown to retain the capacity to include and to enhance the solubility of pharmacologically active molecules.

Synthesis and biological activity of O-glycosylated morphiceptin analogues

The synthesis and biological activity of [Hyp4]morphiceptin and two glycosyl derivatives are reported. Glycopeptide amides were obtained using Fmoc solid-phase chemistry and mild conditions for cleavage from a tris(alkoxy)benzylamide (PAL) resin. Analogues were evaluated in the guinea pig ileum in vitro assay and in in vivo tail-flick and paw-pressure antinociceptive tests after intrathecal administration in rats. Substitution of Pro4 by Hypo4 and further derivatization of Hyp with glucose or galactose, resulted in an unexpected decrease in biological activity with respect to morphiceptin.

Characterization of a high molecular mass cytokinin-like compound extracted from wheat germ ( Triticum vulgare L.)

We describe the presence of a glycosyl derivative from wheat germ with a cytokinin activity. This compound was isolated after extraction by four chromatography steps: sulfopropyl ion exchange, Sephadex LH-20, Trisacryl GF 05 gel filtration and cellulose thin-layer chromatography. Glucose and xylose were identified by gas chromatography in the ratio 2:1. This glycosylated derivative has a maximal absorption at 277 nm due to an expected aglycone. After peracetylation, the molecular mass obtained in FAB mass spectrometry was 1333 in positive mode ( M + H) + and 1331, in negative mode ( M − H) − . This compound showed an optimal activity on the cucumber cotyledon assay at 4 × 10 −5 M equivalent concentration of 6-benzylaminopurine.

Flavonoid chemistry of Siphonoglossa

Seven species of Siphonoglossa section Siphonoglossa were found to elaborate only apigenin-based C -glycosylflavones that are methylated either at the 7- and 4′-positions, only the 7-position, or are not methylated at all. Fourteen C -glucosyl derivatives of apigenin including the 6- C -glucosyl types 6- C -glucosylapigenin 7,4′-dimethyl ether (embigenin, reported here for the first time), embinin, isovitexin, swertisin and some 2′- O -glycosyl derivatives of these latter two compounds, were obtained from these species. The 8- C -glucosyl (i.e. isoembigenin, vitexin) and 6,8-di- C -glycosyl (i.e. vicenin-2) types occur less frequently in the species investigated here. The flavonoid chemistry correlates with other sources of data suggesting that the species of this section form a natural group.

Ellagic compounds from Diplopanax stachyanthus

The stem bark of Diplopanax stachyanthus contains the phenolic lactones 3,3′,4′-tri- O-methylellagic acid, 3,3′,4′-tri- O-methylellagic acid 4- O-β- d-glucopyranoside and a new ellagic acid glycoside, 3,3′-di- O-methylellagic acid 4- O-β- d-xylopyranoside. The 13C NMR O-acetyl substituent effects were most useful for characterizing ellagic acid O-di- and trimethyl ethers. These effects are extended to some simple glycosyl derivatives where it is demonstrated not only that the anomeric configuration but also the exact site of the sugar substitution can be determined from such data.

Isolation of a cytosolic β-glucosidase from calf liver and characterization of its active site with alkyl glucosides and basic glycosyl derivatives

A β-glucosidase/β-galactosidase with M r 52,500 was isolated from calf liver cytosol by a four-step procedure incorporating affinity chromatography on N-(9-carboxynonyl)-deoxynojirimycin-AH-Sepharose. Its pH optimum was at 5.8 with half-maximal activity at pH 3.5 and 8.6. Affinity for gluco compounds expressed by K m or K i , of substrates and inhibitors was 2- to 10-fold higher than for the corresponding galacto compounds. Alkyl glucosides were hydrolyzed with lower V max than p-nitrophenyl and 4-methylumbelliferyl glucosides, but due to their higher affinity the alkyl glucosides displayed values for k cat K m of the same magnitude of the aryl glucosides when the alkyl chains were longer than octyl. Glucosylsphingosine was bound with K i (= K m) 2.2 μ m and hydrolyzed with a V max that was 50-fold lower than the V max for 4-methylumbelliferyl β-glucoside. The product sphingosine was inhibitory with K i 0.30 μM. A systematic study with alkyl glucosides and glucosylamines defined the aglycon site as a narrow, strongly hydrophobic cleft able to accommodate up to 10 methylene groups. Each CH 2 group contributed 3.1 kJ/mol to the standard free energy of binding. The inhibition by gluco-and galactosylamine and by 1-deoxynojirimycin and its D- galacto analog was ~200-fold better than by corresponding nonbasic compounds. pH dependence of the inhibition and comparison with permanently cationic glycosyl derivatives showed that the nonprotonated form was the inhibiting species. This feature puts the cytosolic β-glucosidase in the large class of glycoside hydrolases which strongly bind basic glycosyl derivatives by their protonation at the active site and formation of a shielded ion pair with the carboxylate of an aspartic or glutamic side chain.

Synthesis of 2′,3′-Dideoxyribavirin

Abstract A synthesis of 1-(2,3-dideoxy-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (2′,3′-dideoxyribavirin, ddR) is described. Glycosylation of the sodium salt of 1,2,4-triazole-3-carbonitrile (5) with 1-chloro-2-deoxy-3,5-di-0-p-toluoyl-α-D-erythro-pentofuranose (1) gave exclusively the corresponding N-1 glycosyl derivative with β-anomeric configuration (6), which on ammonolysis provided a convenient synthesis of 2′-deoxyribavirin (7). Similar glycosylation of the sodium salt of methyl 1,2,4-triazole-3-carboxylate (2) with 1 gave a mixture of corresponding N-1 and N-2 glycosyl derivatives (3) and (4), respectively. Ammonolysis of 3 furnished yet another route to 7. A four-step deoxygenation procedure using imidazolylthiocarbonylation of the 3′-hydroxy group of 5′-0-toluoyl derivative (9a) gave ddR (11). The structure of 11 was proven by single crystal X-ray studies. In a preliminary in vitro study ddR was found to be inactive against HIV retrovirus.

Synthesis of 7-Glycopyranosyl-5-oxq-pyrrolo[2,3-d]Pyrimidine and 4-Glyco Pyranosylamino-Furo[2,3-d]Pyrimidine Derivatives

Abstract The synthesis of some glycosyl derivatives of furo[2,3-d] and pyrrolo[2,3-d]pyrimidines is described.

Synthesis of certain 3‐alkoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidines structurally related to adenosine, inosine and guanosine

AbstractSeveral 3‐alkoxysubstituted pyrazolo[3,4‐d]pyrimidine ribonucleosides structurally related to adenosine, inosine and guanosine have been prepared by the direct glycosylation of preformed aglycon precursor containing a 3‐alkoxy substituent. Ring closure of 5(3)‐amino‐3(5)‐ethoxypyrazole‐4‐carboxamide (6b) with either formamide or potassium ethyl xanthate gave 3‐ethoxyallopurinol (7b) and 3‐ethoxy‐6‐thioxopyrazolo[3,4‐d]‐pyrimidin‐4(5H,7H)‐one (10), respectively. Methylation of 10 gave the corresponding 6‐methylthio derivative 15. Similar ring annulation of 5(3)‐methoxypyrazole‐4‐carboxamide (6a) with formamide afforded 3‐methoxyallopurinol (7a). Treatment of 5(3)‐amino‐3(5)‐methoxypyrazole‐4‐carbonitrile (5a) with formamidine acetate furnished 4‐amino‐3‐methoxypyrazolo[3,4‐d]pyrimidine (4). High‐temperature glycosylation of 7b with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose in the presence of boron trifluoride etherate gave a 2:1 mixture of N‐1 and N‐2 glycosyl blocked nucleosides 11b and 13b. Deprotection of 11b and 13b with sodium methoxide gave 3‐ethoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (12b) and the corresponding N‐2 glycosyl isomer 14b, respectively. Similar glycosylation of either 4 or 7a, and subsequent debenzoylation gave exclusively 4‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidine (9) and 3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4‐(5H)‐one (12a), respectively. The structural assignment of 12a was made on the basis of single‐crystal X‐ray analysis. Application of this general glycosylation procedure to 15 gave the corresponding N‐1 glycosyl derivative 16 as the sole product, which on debenzoylation afforded 3‐ethoxy‐6‐(methylthio)‐1‐(3‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (17). Oxidation of 16 and subsequent ammonolysis furnished the guanosine analog 6‐arnino‐3‐ethoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]‐pyrimidin‐4(5H)‐one (19). Similarly, starting from 3‐methoxy‐4,6‐bis(methylthio)pyrazolo[3,4‐d]pyrimidine (20), 6‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (23) was prepared.

Synthese D'Azotures et de Benzoates de Glycosyle a Partir de Sulfites Cycliques Enc C-1, C-2

Abstract The reaction of sugars bearing a cyclic sulfite group on C-1, C-2 with azide or benzoate ions, is strereoselective and gives trans- 1,2 glycosyl azides or glycosyl benzoates with a free hydroxyle at C-2. The reaction is performed under mild conditions and gives excellent yields of glycosyl derivatives.

Synthesis of β‐D‐ribo‐ and 2′‐deoxy‐β‐D‐ribofuranosyl derivatives of 6‐aminopyrazolo[4,3‐c]pyridin‐4(5H)‐one by a ring closure of pyrazole nucleoside precursors

Abstract6‐Amino‐1‐(2‐deoxy‐β‐D‐erthro‐pentofuranosyl)pyrazolo[4,3‐c]pyridin‐4(5H)‐one (5), as well as 2‐(β‐D‐ribofuranosyl)‐ and 2‐(2‐deoxy‐β‐D‐ribofuranosyl)‐ derivatives of 6‐aminopyrazolo[4,3‐c]pyridin‐4(5H)‐one (18 and 22, respectively) have been synthesized by a base‐catalyzed ring closure of pyrazole nucleoside precursors. Glycosylation of the sodium salt of methyl 3(5)‐cyanomethylpyrazole‐4‐carboxylate (6) with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranose (8) provided the corresponding N‐1 and N‐2 glycosyl derivatives (9 and 10, respectively). Debenzoylation of 9 and 10 with sodium methoxide gave deprotected nucleosides 14 and 16, respectively. Further ammonolysis of 14 and 16 afforded 5(or 3)‐cyanomethyl‐1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)pyrazole‐4‐carboxamide (15 and 17, respectively). Ring closure of 15 and 17 in the presence of sodium carbonate gave 5 and 22, respectively. By contrast, glycosylation of the sodium salt of 6 with 2,3,5‐tri‐O‐benzoyl‐D‐ribofuranosyl bromide (11) or the persilylated 6 with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose gave mainly the N‐2 glycosylated derivative 13, which on ammonolysis and ring closure furnished 18. Phosphorylation of 18 gave 6‐amino‐2‐β‐D‐ribofuranosylpyrazolo[4,3‐c]pyridin‐4(5H)‐one 5′‐phosphate (19). The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1H nmr and uv spectral characteristics and by single‐crystal X‐ray analysis of 16.