Conformations of methyl 2,5-di-O-acetyl-beta-D-glucofuranosidurono-6,3-lactone and 1,2,5-tri-O-acetyl-beta-D-glucofuranurono-6,3-lactone in the crystal structure and in solution

The single-crystal X-ray diffraction and high-resolution 1H and 13C NMR spectral data for methyl 2,5-di-O-acetyl-beta-D-glucofuranosidurono-6,3-lactone and 1,2,5-tri-O-acetyl-beta-D-glucofuranurono-6,3-lactone are reported. The lactones were synthesized as byproducts of reactions carried out to obtain methyl 1,2,3,4-tetra-O-acetyl-D-glucopyranuronate. The conformations of these lactones in the crystal structure and in solution are discussed. A 1T2-like conformation was found to be the preferred form for these lactones in both the crystal lattice and in solution.     

Rapid access to uronic acid-based mimetics of Kdn2en from D-glucurono-6,3-lactone

A concise route to novel mimetics of Kdn2en, based on delta4-uronic acids, from D-glucurono-6,3-lactone is presented. Uronic acid-based mimetics in which an aliphatic ether (O-glycoside), a thioether (S-glycoside), or acetamide takes the place of the natural C-6 glycerol sidechain of the sialic acid were synthesized from the key intermediate, methyl 2,3,4-tri-O-acetyl-alpha-D-glucopyranosyluronate bromide.     

Beta-anomeric selectivity in the glycosidation of D-mannofuranurono-6,3-lactone catalyzed by boron trifluoride diethyl etherate

The BF3-promoted glycosylation of D-mannofuranurono-6,3-lactone with dodecanol or methanol afforded n-alkyl beta-D-mannofuranosidurono-6,3-lactone. Reduction of n-dodecyl beta-D-mannofuranosidurono-6,3-lactone with sodium borohydride yielded the corresponding alkyl beta-D-mannofuranoside.     

Synthesis of 2'-deoxy-6,3'-methano-cyclo-pyrimidine nucleosides

The nucleophilic attack of lithiated pyrimidines to a suitably-protected 3-ketosugar, afforded the 3-branched sugar stereospecifically, followed by intramolecular glycosylation to give 6,3'-methano-cyclo-pyrimidine nucleosides. The 2'-deoxygenation was achieved by sequential protection, deprotection and radical reduction.     

Synthesis of L-glucose from D-gulono-1,4-lactone

An efficient method for the synthesis of L-glucose from D-gulono-1,4-lactone via 1,2,3,4,5-penta-O-benzyl/acetyl/benzoyl-D-gulitol is described in 34-53% overall yield.     

Synthesis of highly water-soluble fibrate derivatives via BGLation

Three water-soluble fibrates (fenofibrate, bezafibrate and chlofibrate) conjugated with a symmetrically branched glyceryl trimer (BGL003) were synthesized, and an evaluation of the fenofibrate–BGL003 conjugate as a candidate for anti-hyperlipemia drug was carried out using rats. The water-solubility of the fenofibrate–BGL003 conjugate was several thousand times greater than that of the original fenofibrate. The lipid-lowering effects of the fenofibrate–BGL003 conjugate were as strong as those of the same grams of fenofibrate. The actual active species of fenofibrate, fenofibric acid, was detected in rats’ blood, but neither the fenofibrate–BGL003 conjugate nor fenofibrate was detected, probably due to enzymatic hydrolysis of the ester bond. The plasma concentration of fenofibric acid derived from the fenofibrate–BGL003 conjugate was five times higher than that derived from fenofibrate 4 h after administration.     

Synthesis of N tau-arylhistidine derivatives via direct N-arylation

N(tau)-Aryl-histidine derivatives were synthesized using a modified one-step Cu-catalyzed coupling of aryl halides and N-acetylhistidine methyl ester. The latter is much less reactive than imidazole toward aryl halides. p-Chloroiodobenzene coupled with iodine displacement only, whereas m- and p-bromoiodobenzene both gave mixtures of bromo- and iodophenyl products.     

Synthesis of guanosine and its derivatives from AICA-riboside

A novel and convenient method for the synthesis of guanosine is described. The reaction of AICA-riboside with sodium methylxanthate gave 2-mercaptoinosine in almost quantitative yield. The latter was oxidized with hydrogen peroxide to afford inosine-2-sulfonic acids, which was readily animated to give guanosine in excellent yield. Similarly, the preparation of N²-methylguanosine and N²,N²-dimethylguanosine, minor constituents of transfer RNA, was also accomplished. Furthermore, this procedure was extended to the synthesis of 2′,3′-O-isopropylideneguanosine and the isopropylidene derivatives of various N²-substituted guanosines from 2′,3′-O-isopropylidene-AICA-riboside. Guanosine via 2′,3′-O-isopropylideneguanosine was successfully phosphorylated to give 5′-guanylic acid.     

Synthesis of penaresidin derivatives and its biological activity

A series of stereoisomers for the azetidine ring of penaresidin B was synthesized and their cytotoxic and antimicrobial activities were evaluated. Among six synthetic isomers 1-6, isomers 4 and 5 showed relatively potent cytotoxic activity against A549 (lung) and HT29 (colon) tumor cells as well as antibacterial activity.     

Regioselective formation of 6-O-acylsucroses and 6,3'-di-O-acylsucroses via the stannylene acetal method

Regioselective formation of 6-O-acylsucroses and 6,3′-di-O-acylsucroses in one pot with good yields was achieved for the first time by a typical acylation method of sucrose via its dibutylstannylene acetal. Pure monoesters at OH-6 and diesters at OH-6,3′ obtained by these procedures were readily isolated by simple column chromatography, thus overcoming the main difficulties associated with regioselectivity, efficiency, and isolation techniques for the practical preparation. Explanations for the regioselectivities observed during this stannylene acetal-mediated reaction were also proposed based on the structures of the stannylene acetal in solution and the intramolecular migration of stannylenes.     

Synthesis of novel quinoxaline derivatives and its cytotoxic activities

Substituted dihydroquinozalin-2-ones (1–16) have been synthesized easily by the use of copper-catalyzed coupling method. The reactions of 2-haloanilines with a variety of α-amino acids in the presence of copper (I) iodide gave corresponding 3-substituted dihydroquinozalin-2-ones in up to 86% yield. Some new quinoxalin-2-ones (2, 4, 5, 13 and 16) have moderate cytotoxic activity toward HeLaS3 cell lines at 4.9–18.1 μM.     

Synthesis of higher-carbon sugars via vinyltin derivatives of simple monosaccharides

6-O-Benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-oct-7-ynopyranose reacted with tributyltin hydride to afford (Z-6-O-benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-8-(tributylstannyl)-l-glycero-α-d-galacto-oct-7-enopyranose, which was subsequently isomerized to the E-olefin 4. Replacement of the tributyltin moietey with lithium in 4 afforded the vinyl anion which reacted with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose, furnishing 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-heptopyranos-7-ylidene] -60-deoxy-1,2-O-isopropylidene-α-d-gluco- (6) and -β-l-ido-furanose (7) in yields of ∼70 or ∼87% (depending on the temperature of the reaction). The configurations of the new chiral centers in 6 and 7 were determined by their conversion into 3-O-benzyl-1,2-O-isopropylidene-α-d-gluco- and -β-l-ido-furanose, respectively. Oxidation of 6 and 7 gave the same enone, 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto- heoptopyranos-7-ylidene]-6-deoxy-1,2-O-isopropylidene-α-d-xylo-hexofuranos-5-ulose.     

Synthesis of novel quaternary chitosan derivatives via N-Chloroacyl-6-O-triphenylmethylchitosans

Various quaternary chitosan derivative structures were synthesized by reacting N-chloroacyl-6-O-triphenylmethylchitosans with tertiary amines. Full substitutions were obtained from the quaternization reactions and the obtained water-soluble quaternary chitosan derivatives were thoroughly characterized with (1)H NMR, (13)C NMR, (1)H-(13)C HSQC NMR, and FT-IR.     

Synthesis and structure-immunosuppressive activity relationships of bakuchiol and its derivatives

A series of derivatives of bakuchiol were synthesized and tested in vitro for their cytotoxicity, and inhibition of T cell proliferation and B cell proliferation. The data obtained provided preliminary structure-activity relationships of the compounds as immunosuppressive activity.     

Synthesis and modification of dibenzylglycine derivatives via the Suzuki-Miyaura cross-coupling reaction.

The objective of this paper is to describe in details of various available methods to prepare C(alpha,alpha)-dibenzylglycine (Dbzg) and then include our work involving the synthesis of side chain Dbzg derivatives. alpha,alpha-Disubstituted amino acids (alpha,alphaAAs) are important members in the family of modified amino acids. Replacement of the alpha-hydrogens of glycine 1 by alkyl groups leads to alpha,alphaAAs. The steric hindrance of the quaternary centre of Aib 2 combined with the helix-forming capacity has attracted the attention of structural biologists and protein crystallographers. Dbzg 3 is a special structural variant of Aib. The presence of two benzyl groups at C(alpha)-position not only impart rigidity to the peptide backbone in which it is incorporated, but also acts as a useful vehicle for studying pi-pi interactions. Although several C(alpha,alpha)-disubstituted glycines such as C(alpha,alpha)-diethyl glycine (Deg), C(alpha,alpha)-dipropyl glycine (Dpg) etc. have been studied in detail, not much has been known about Dbzg because of limited availability of synthetic procedures. Various Dbzg derivatives 19a-f have been prepared using ethyl isocyanoacetate 14 as a glycine equivalent (eq.). A useful and simple methodology has been developed using the Suzuki-Miyaura cross-coupling reaction for the modification of Dbzg derivatives 17d, 19d, 22. Using this 'Building Block Approach' (Accounts of Chemical Research 36, 2003, 342) one can generate a variety of Dbzg derivatives 20a-f and 23a-e, which may find useful applications in combinatorial synthesis and QSAR studies.     

Synthesis of peptide aldehydes via enzymatic acylation of amino aldehyde derivatives

Two ways for semi-enzymatic preparation of the peptide aldehydes are proposed: (1) enzymatic acylation of amino alcohols with acyl peptide esters and subsequent chemical oxidation of the resulting peptide alcohols with DMSO/acetic anhydride mixture or (2) enzymatic acylation of the preliminarily obtained by a chemical route amino aldehyde semicarbazones. Subtilisin 72, serine proteinase with a broad specificity, distributed over macroporous silica, was used as a catalyst in both cases. Due to the practical absence of water in the reaction mixtures the yields of the products in both enzymatic reactions were nearly quantitative. The second way seems to be more attractive because all chemical stages were carried out with amino acid derivatives, far less valuable compounds than peptide ones. A series of peptide aldehydes of general formula Z-Ala-Ala-Xaa-al (where Xaa-al=leucinal, phenylalaninal, alaninal, valinal) was obtained. The inhibition parameters for these compounds, in the hydrolysis reactions of corresponding chromogenic substrates for subtilisin and -chymotrypsin, were determined.     

Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives

One of the known cytotoxic lignans is (-)-1-O-feruloyl-secoisolariciresinol designated as hanultarin, which was isolated from the seeds of Trichosanthes kirilowii. In this Letter, we described the first synthesis of 1-O-feruloyl-secoisolariciresinol, 1,4-O-diferuloyl-secoisolariceresinol and their analogues. The cytotoxicities of these compounds were evaluated against several cancer cell lines. Interestingly, we found that the feruloyl diester derivative of secoisolariciresinol was the most active cytotoxic compound against all the cancer cells tested in this experiment. The IC(50) values of the1,4-O-diferuloyl-secoisolariceresinol were in the range of 7.1-9.8μM except one cell line. In considering that both ferulic acid and secoisolariciresinol are commonly found in many plants and have no cytotoxicity, this finding is remarkable in that simple covalent bonds between the ferulic acid and secoisolariciresinol cause a cytotoxic effect.     

Synthesis of orthogonally reactive FK506 derivatives via olefin cross metathesis

Chemical inducers of dimerization (CIDs) are employed in a wide range of biological applications to control protein localization, modulate protein–protein interactions and improve drug lifetimes. These bifunctional chemical probes are assembled from two synthetic modules, which each provide affinity for a distinct protein target. FK506 and its derivatives are often employed as modules in the syntheses of these bifunctional constructs, owing to the abundance and favorable distribution of their target, FK506-binding protein (FKBP). However, the structural complexity of FK506 necessitates multi-step syntheses and/or multiple protection–deprotection schemes prior to installation into CIDs. In this work, we describe an efficient, one-step synthesis of FK506 derivatives through a selective, microwave-accelerated, cross metathesis diversification step of the C39 terminal alkene. Using this approach, FK506 is modified with an array of functional groups, including primary amines and carboxylic acids, which make the resulting derivatives suitable for the modular assembly of CIDs. To illustrate this idea, we report the synthesis of a heterobifunctional HIV protease inhibitor.     

Synthesis and characterization of 5-hydroxymethyl-5-methyl-pyrroline N-oxide and its derivatives

Synthesis and spin trapping behavior of three novel DMPO derivatives, namely 5-hydroxymethyl-5-methyl-pyrroline N-oxide (HMMPO), 5-(2-furanyl)-oxymethyl-5-methyl-pyrroline N-oxide (FMMPO), and 5-(2-pyranyl)-oxymethyl-5-methyl-pyrroline N-oxide (PMMPO) towards different oxygen- and carbon-centered radicals are described. The stabilizing effect of a series of cyclodextrins on the superoxide adducts was tested.