Molecular Recognition and Cooperative Binding Ability of Fluorescent Dyes by Bridged Bisβ-cyclodextrin)s Tethered with Aromatic Diamine

A novel bridged bis(β-cyclodextrin),m-phenylenediimino-bridged bis(6-imino-6-deoxy-β-cyclodextrin) (2), was synthesized by the reaction of m-phenylenediamine and 6-deoxy-6-formyl-β-cyclodextrin. The inclusion complexation behavior of the novel bridged bis(β-cyclodextrin) 2,as well as native β-cyclodextrin (1),p-phenylenediamino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (3) and 4,4'-bianilino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (4) with representative fluorescent dye molecules, i.e., acridine red (AR), neutral red (NR), Rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonate (ANS) and sodium 6-toluidino-2-naphthalenesulfonate (TNS), was investigated at 25 °C in aqueous phosphate buffer solution (pH 7.20) by means of fluorescence, and circular dichroism, as well as 2D NMR spectrometry. The spectrofluorometric titrations have been performed to calculate the complex stability constants (K_S) and Gibbs free energy changes (Δ G°) for the stoichiometric 1 : 1 inclusion complexation of 1–4 with fluorescent dye molecules. The results obtained demonstrated that bis(β-cyclodextrin)s 2–4 showed much higher affinities toward these guest dyesthan native β-cyclodextrin 1. Typically, dimer 2 displayed the highest binding ability upon inclusion complexation with ANS, affording 35 times higher K_S value than native β-cyclodextrin. The significantlyenhanced binding abilities of these bis(β-cyclodextrin)s are discussed from thebinding mode and viewpoints of size/shape-fit concept and multiple recognition mechanism.     

Dimerisation and complexation of 6-(4′-t-butylphenylamino)naphthalene-2-sulphonate by β-cyclodextrin and linked β-cyclodextrin dimers

This study shows that stereochemical factors largely determine the extent to which 6-(4′-t-butylphenylamino)-naphthalene-2-sulphonate, BNS^?  and its dimer, (BNS^? )₂, are complexed by β-cyclodextrin, βCD, and a range of linked βCD dimers. Fluorescence and ¹H NMR studies, respectively, show that BNS^?  and (BNS^? )₂ form host–guest complexes with βCD of the stoichiometry βCD.BNS^?  (10^? 4 K ₁ = 4.67 dm³ mol^? 1) and βCD.BNS₂ ^2 ?  (10^? 2 K ₂′ = 2.31 dm³ mol^? 1), where the complexation constant K ₁ = [βCD.BNS^? ]/([βCD][BNS^? ]) and K ₂′ = [βCD. (BNS^? )₂]/([βCD.BNS^? ][BNS^? ]) in aqueous phosphate buffer at pH 7.0, I = 0.10 mol dm³ at 298.2 K. (The dimerisation of BNS^?  is characterised by 10^? 2 K _d = 2.65 dm³ mol^? 1.) For N,N-bis((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)succinamide, 33βCD₂su, N-((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)-N′-(6^A-deoxy-6^A-β-cyclodextrin)urea, 36βCD₂su, N,N-bis(6^A-deoxy-6^A-β-cyclodextrin)succinamide, 66βCD₂su, N-((2^AS,3^AS)-3^A-deoxy-3^A-β-cyclodextrin)-N′-(6^A-deoxy-6^A-β-cyclodextrin)urea, 36βCD₂ur, and N,N-bis(6^A-deoxy-6^A-β-cyclodextrin)urea, 66βCD₂ur, the analogous 10^? 4 K ₁ = 11.0, 101, 330, 29.6 and 435 dm³ mol^? 1 and 10^? 2 K ₂′ = 2.56, 2.31, 2.59, 1.82 and 1.72 dm³ mol^? 1, respectively. A similar variation occurs in K ₁ derived by UV–vis methods. The factors causing the variations in K ₁ and K ₂ are discussed in conjunction with ¹H ROESY NMR and molecular modelling studies.     

Synthesis of the first per(3-deoxy)-cyclooligosaccharide: hepta(manno-3-deoxy-6-O-t-butyldimethylsilyl)-β-cyclodextrin

Reduction of hepta(manno-2,3-anhydro-6-O-t-butyldimethylsilyl)-β-cyclodextrin with lithium triethylborohydride gives hepta(manno-3-deoxy-6-O-t-butyldimethylsilyl)-β-cyclodextrin. This compound plus the hepta(2-O-methyl)- and hepta(2-O-benzyl)-derivatives all have the ⁴C₁ conformation. Capillary GC columns manufactured with hepta(manno-2,3-anhydro-, hepta(manno-3-deoxy-2-O-methyl- and hepta(manno-2-O-benzyl-6-O-t-butyldimethylsilyl)-β-cyclodextrin stationary phases were evaluated for enantio-discrimination with 39 non-polar racemic analytes. The GC column coated with the benzyl derivative showed enantioselectivity comparable to, and in some cases superior to, a commercial per(methyl)-β-cyclodextrin column. The other columns showed little or no enantio-discrimination. A thermodynamics study established a linear enthalpy–entropy compensation effect for two series of analytes on the commercial permethyl-β-cyclodextrin column, but not for the column coated with the benzyl derivative.     

Correlation between Thermodynamic Behavior and Structure in the Complexation of Modified β-Cyclodextrins and Bile Salts

Complex stability constants (K _S), standard molar enthalpy changes (ΔH ⁰) and entropy changes (ΔS ⁰) for the inclusion complexation of two cyclodextrin dimers, 6,6′-{2,2′-diselenobis[2-(benzoylamino)ethylamino]}-bridged bis(β-cyclodextrin) (1) and o-phenylenediseleno bridged bis(β-cyclodextrin)s (3), and their monomer analogs, 6-deoxy-6-{[2-(2,3-dihydro-3-oxo-1,2-benzisoselenazol-2-yl)ethyl]amino}-β-cyclodextrin (2) and mono[6-(phenylseleno)-6-deoxy]-β-cyclodextrin (4), with two bile salt guests, sodium cholate (CA) and sodium deoxycholate (DCA), were determined at 25°C in Tris buffer solutions (pH 7.4) at 298.15?K by means of isothermal titration microcalorimetry (ITC). The interactions and binding modes between the host cyclodextrins and the guest bile salts were further studied by ROESY spectroscopy. The thermodynamic parameters obtained, together with the ROESY spectra, were used to examine the correlations between thermodynamic behavior and binding modes of the host–guest complexation. The results indicate that the length, structure and conformation of the tethers linked to the cyclodextrins determine the binding modes and the binding abilities between hosts and guests to a great extent, leading to a reversion in binding ability when comparing the corresponding dimer and its monomer analog.     

Synthesis and Polymerization of Carbamate-Linked Cyclodextrin Methacrylate Monomers

Abstract

A one-step synthesis for cyclodextrin methacrylate monomers was examined starting from α-, β- and γ-cyclodextrin. The reaction of 2-isocyanatoethyl methacrylate as well as allylisocyanate with the corresponding cyclodextrin gave the monofunctionalized carbamate-linked cyclodextrin methacrylates 2, 6 and 9 and allylcarbamates 11 and 14 in moderate yields. By NMR spectroscopic means, it could be proven that in all cases only the primary 6-hydroxyl groups of the cyclodextrins reacted with the isocyanate group. For the synthesis of a β-cyclodextrin monoallyl compound, a substitution reaction of purchasable 6-O-monotoluenesulfonyl-β-cyclodextrin with allylamine gave 6-N-allylamino-6-deoxy-β-cyclodextrin 18 in high yield. The reaction of 2-isocyanatoethyl methacrylate with α-cyclodextrin to the 6-O-carbamoyl-2-methylpropenoylethyl-α-cyclodextrin (2) was optimized so that the monomer 2 could be prepared on a larger scale without chromatographic separation. The aqueous radical homopolymerization of 2 with the peroxodisulfate/bisulfite redox initiator gave the water soluble cyclodextrin polymer 19 in good yield. Its molecular weight was determined by gel permeation chromatography to be M_n = 101,800 corresponding to an average degree of polymerization P_n = 90.     

Application of Phenyl 1-Selenoglycosides in the Synthesis of a Cell-Wall Tetrameric Fragment of Proteus Vulgaris Strain 5/43

Abstract

DAST-assisted rearrangement of 3-O-allyl-4-O-benzyl-α-l-rhamnopyranosyl azide followed by treatment of the generated fluorides with ethanethiol and BF₃·OEt₂ gave glycosyl donor ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside. Stereoselective glycosylation of methyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside with ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside, under the agency of NIS/TfOH afforded methyl 3-O-(3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzyli-dene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Removal of the allyl function of the latter dimer, followed by condensation with properly protected 2-azido-2-deoxy-glucosyl donors, in the presence of suitable promoters, yielded selectively methyl 3-O-(3-O-[6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-α-D-glucopyranosyl]-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Deacetylation and subsequent glycosylation of the free HO-6 with phenyl 2,3,4,6-tetra-O-benzoyl-1-seleno-β-D-glucopyranoside in the presence of NIS/TfOH furnished a fully protected tetrasaccharide. Deprotection then gave methyl 3-O-(3-O-[6-O-{β-D-glucopyranosyl}-2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-acetamido-2,6-dideoxy-α-L-glucopyranosyl)-2-acetamido-2-deoxy-β-D-glucopyranoside.     

Heptakis(6-deoxy-6-guanidino)-β-cyclodextrin: an artificial model for mitochondrial ADP/ATP carrier

Heptakis(6-deoxy-6-guanidino)-β-cyclodextrin, prepared by one-step reaction of heptakis(6-amino-6-deoxy)-β-cyclodextrin with 1H-pyrozolecarboxamidine, binds ADP/ATP very tightly.     

Molecular Recognition of Aliphatic Alcohols and Carboxylic Acid by Chromophoric Cyclodextrins

Abstract

Molecular recognition behavior of eight cyclodextrin derivatives, i.e. mono(6-pyridinio-6-deoxy)-α-cyclodextrin (1α), mono(6-pyridinio-6-deoxy)-β-cyclodetrin (1β), mono(6-pyridinio-6-deoxy)-γ-cyclodextrin (1γ), mono[6-(p-picolinio)-6-deoxy]-β-cyclodextrin (2β), mono(6-anilino-6-deoxy)-β-cyclodextrin (3β), mono[6-(m-toluidino)-6-deoxy]-β-cyclodextrin (4β), mono[6-O-(8-quinolyl)]-β-cyclodextrin (5β), and novel mono[6-(2-naphthylamino)-6-deoxy]-β-cyclodextrin (6β), with a series of aliphatic alcohols and carboxylic acid has been investigated spectroscopically. Using the appended aromatic group as a spectral probe, spectroflurometric or spectropolarimetric titrations have been performed at 25°C in aqueous phosphate buffer solution (pH 7.20, 0.1 M) to determine the complex stability constants (K_s ) and Gibbs free energy changes (-δG°) for the stoichiometric 1:1 inclusion complexation of cyclodextrin derivatives with the guests. The results obtained demonstrate that the modified cyclodextrins are highly sensitive to the size/shape and hydrophobicity of guest molecules, and particularly 5β gives an excellent molecular selectivity up to 215 for 1-adamantanol/cyclohexanol. The binding ability and selectivity of the modified cyclodextrins (1α, 1β, and 1β-6β) are discussed from the view points of size/shape-fit concept, induced-fit interaction, and the multiple recognition mechanisms.     

Nucleoside und Nucleotide. Teil 15. Synthese von Desoxyribonucleosid-monophosphaten und -triphosphaten mit 2(1H)-Pyrimidinon, 2(1H)-Pyridinon und 4-Amino-2(1H)-pyridinon als Basen

Nucleosides and Nucleotide. Part 15. Synthesis of Deoxyribonucleoside Monophosphates and Triphosphates with 2(1H)-Pyrimidinone, 2(1H)-Pyridinone and 4-Amino-2(1H)-pyridinone as the Bases The phosphorylation of the modified nucleosides 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone (M_d, 4 ), 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone (Z_d, 6 ) and the synthesis of 1–2′-deoxy-β-D -ribofuranosyl-2(1 H)-pyrimidinone-5′-O-triphosphate (pppM_d, 1 ), 1-(2′-deoxy-β-D ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppII_d, 2 ), and 4-amino-1-(2′-deoxy-βD -ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppZ_d, 3 ) are described. The nucleoside-5′-monophosphates pM_d (5) and pZ_d (7) were obtained by selective phosphorylation of M_d (4) and Z_d (6) , respectively, using phosphorylchloride in triethyl phosphate or in acetonitril. The reaction of pM_d (5) pII _d (8) or pZ_d (7) with morpholine in the presence of DCC led to the phosphoric amides 9, 10 and 11 , respectively, which were converted with tributylammonium pyrophosphate in dried dimethylsulfoxide to the nucleoside-5′triphosphates 1, 2 and 3 , respectively.     

Novel fluorinated amphiphilic cyclodextrin derivatives: Synthesis of mono-, di- and heptakis-(6-deoxy-6-perfluoroalkylthio)-β-cyclodextrins

A new series of fluorinated amphiphilic β-cyclodextrin derivatives has been synthesized. The strategy is based on the modification of the C-6 position of the mono-6-deoxy-6^A-para-tolylsulfonyl, di-6^A, 6^D-deoxy-6^A, 6^D-(para-tolylsulfonyl) and heptakis-(6-deoxy-6-iodo)-β-cyclodextrin precursors. The synthesis lead to mono-perfluoroalkylthio-, di-perfluoroalkylthio- and heptakis-perfluoroalkylthio-β-cyclodextrin in excellent yields (90-99%).     

Molecular recognition of naphthalenediamine by polyamine modified β-cyclodextrin:yttrium metal complexes

The 6-OH group of β-cyclodextrin was modified by diethylene triamine and triethylene tetramine, respectively, mono[6-diethylenetriamino]-6-deoxy-β-cyclodextrin (DTCD) and mono[6-triethylenetetraamino]-6-deoxy-β-cyclodextrin (TTCD) were synthesized, which included 1,5-naphthalenediamine and 1,8-naphthalenediamine, respectively, in the presence of rare earth metal yttrium chloride. As a result, four ternary inclusion complexes (host–guest-metal) formed, which were characterized via ¹HNMR spectroscopy. The chemical shift variations of host and guest molecules were studied. The stoichiometric proportion of host and guest molecules is 2:1 for all the complexes. Signal degeneration still exists for the guest molecules after the inclusion process, which verifies the symmetrical conformation of guest molecules inside the cavities of two host molecules. All the four complexes exhibit “sandwich”-typed structure.     

Purine nucleosides XXVIII. The synthesis of 7-(2′-deoxy-α- and β-d-ribofuranosyl)purines from 2′-deoxyribofuranosylimidazoles. Preparation of the 2′-deoxy derivative of the nucleoside from pseudovitamin B12 factor G

The synthesis of 1-(2′-deoxyribofuranosyl)imidazoles have been achieved for the first time via the fusion method of glycosidation. 4-Amino-5-carboxamido-1-(2′-deoxy-α-D-ribofuranosyl)-imidazole ( 8 ) and 4-amino-5-carboxamido-1-(2′-deoxy-β-D-ribofuranosyl)imidazole ( 10 ) have been obtained and their structures established by spectroscopic methods. The first examples of 7-(2′-deoxyglycosyl)purines [7-(2′-deoxy-α-D-ribofuranosyl)hypoxanthine ( 6 ) and 7-(2′-deoxy-β-D-ribofuranosyl)hypoxanthine ( 11 )] have been obtained from the requisite 2′-deoxyribofuranosylimidazoles. The preparation of 6 has furnished the 2′-deoxy derivative (α-configuration) of the nucleoside from pseudovitamin B₁₂ Factor G, which constitutes the first 2′-deoxy derivative of any nucleoside isolated from the various naturally occurring pseudovitamin B₁₂ factors.     

单-马来二腈基二硫烯-β-环糊精异构体在溶液中的不同组装行为

通过单-2-对甲苯磺酰基-β-环糊精(1)与马来二腈基二硫烯钠盐的取代反应制得单-2-马来二腈基二硫烯-β-环糊精(2),并经红外光谱、紫外光谱、热重分析、1H和13C NMR等手段对产物进行了表征.虽然化合物2的异构体--单-6-马来二腈基二硫烯9-β-环糊精在溶液中因为相互包合作用而在圆二色性光谱中产生分裂的Cot...     

2,3-Alloepithio-2,3-dideoxy-β-cyclodextrin: synthesis and application in the construction of rigid elliptical cavities with functionality at the secondary hydroxyl side

2^A,3^A-Alloepithio-2^A,3^A-dideoxy-β-cyclodextrin (2), which may serve as a novel and important intermediate for the functionalization of the secondary face of β-cyclodextrin, was prepared in 40% yield by heating 2^A,3^A-mannoepoxy-β-cyclodextrin and thiourea in water. Treatment of 2 with AgNO₃ in the presence of amines afforded 3^A,6^A-anhydro-2^A-deoxy-2^A-thio-β-cyclodextrin (4) in 73% yield. The latter is an artificial enzyme candidate with a specifically orientated thiol group and a rigid elliptical cavity.     

Strukturelle Abwandlungen an partiell silylierten Kohlenhydraten mittels Triphenylphosphin/Azodicarbonsäure-diäthylester. 3. Mitteilung [1]

Structural Modification on Partially Silylated Carbohydrates by Means of Triphenylphosphine/Diethyl Azodicarboxylate Reaction of methyl 2, 6-bis-O-(t-butyldimethylsilyl)-β-D -glucopyranoside ( 1a ) with triphenylphosphine (TPP)/diethyl azodicarboxylate (DEAD) and Ph₃P · HBr or methyl iodide yields methyl 3-bromo-2, 6-bis-O-(t-butyldimethylsilyl)-3-deoxy-β-D -allopyranoside ( 3a ) and the corresponding 3-deoxy-3-iodo-alloside 3c (Scheme 1). By a similar way methyl 2, 6-bis-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 2a ) can be converted to the 4-bromo-4-deoxy-galactoside 4a and the 4-deoxy-4-iodo-galactoside 4b . In the absence of an external nucleophile the sugar derivatives 1a and 2a react with TPP/DEAD to form the 3,4-anhydro-α- or -β-D -galactosides 5 and 6a , respectively, while methyl 4, 6-bis-O-(t-butyldimethylsilyl)-β-D -glucopyranoside ( 1b ) yields methyl 2,3-anhydro-4, 6-bis-O-(t-butyldimethylsilyl)-β-D -allopyranoside ( 7a , s. Scheme 2). Even the monosilylated sugar methyl 6-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 2b ) can be transformed to methyl 2,3-anhydro-6-O-(t-butyldimethylsilyl)-β-D -allopyranoside ( 8 ; 56%) and 3,4-anhydro-α-D -alloside 9 (23%, s. Scheme 3). Reaction of 1c with TPP/DEAD/HN₃ leads to methyl 3-azido-6-O-(t-butyldimethylsilyl)-3-deoxy-β-D -allopyranoside ( 10 ). The epoxides 7 and 8 were converted with NaN₃/NH₄Cl to the 2-azido-2-deoxy-altrosides 11 and 13 , respectively, and the 3-azido-3-deoxy-glucosides 12 and 14 , respectively (Scheme 4 and 5). Reaction of 7 and 8 with TPP/DEAD/HN₃ or p-nitrobenzoic acid afforded methyl 2,3-anhydro-4-azido-6-O-(t-butyldimethylsilyl)-4-deoxy-α- and -β-D -gulopyranoside ( 15 and 17 ), respectively, or methyl 2,3-anhydro-6-O-(t-butyldimethylsilyl)-4-O-(p-nitrobenzoyl)-α- and -β-D -gulopyranoside ( 16 and 18 ), respectively, without any opening of the oxirane ring (s. Scheme 6). - The 2-acetamido-2-deoxy-glucosides 19a and 20a react with TPP/DEAD alone to form the corresponding methyl 2-acetamido-3,4-anhydro-6-O-(t-butyldimethylsilyl)-2-deoxy-galactopyranosides ( 21 and 22 ) in a yield of 80 and 85%, respectively (Scheme 7). With TPP/DEAD/HN₃ 20a is transformed to methyl 2-acetamido-3-azido-6-O-(t-butyldimethylsilyl)-2,3-didesoxy-β-D -allopyranoside ( 25 , Scheme 8). By this way methyl 2-acetamido-3,6-bis-O-(t-butyldimethylsilyl)-α-D -glucopyranoside ( 19b ) yields methyl 2-acetamido-4-azido-3,6-bis-O-(t-butyldimethylsilyl)-2,4-dideoxy-α-D -galactopyranoside ( 23 ; 16%) and the isomerized product methyl 2-acetamido-4,6-bis-O-(t-butyldimethylsilyl)-2-deoxy-α-D -glucopyranoside ( 19d ; 45%). Under the same conditions the disilylated methyl 2-acetamido-2-deoxy-glucoside 20b leads to methyl 2-acetamido-4-azido-3,6-bis-O-(t-butyldimethylsilyl)-2,4-dideoxy-β-D -galactopyranoside ( 24 ). - All Structures were assigned by ¹H-NMR. analysis of the corresponding acetates.     

β-Biguanidinium-cyclodextrin: a supramolecular mimic of mitochondrial ADP/ATP carrier protein

We reported a novel mono-β-cyclodextrin derivative, mono-6-deoxy-6-biguanidino-β-cyclodextrin (β-biGCD), which was investigated as a mimic of ADP/ATP carrier (AAC). Its affinity toward AMP, ADP, and ATP was evaluated by means of isothermal titration calorimetry (ITC). The association constants (K_a) of β-biGCD binding to AMP, ADP, and ATP were determined to be (1.07±0.04)×10⁶, (5.86±0.02)×10⁶, and (4.33±0.06)×10⁶ L mol⁻¹, respectively, which were 100-fold higher than mono-guanidino-β-cyclodextrin (ca. 10⁴ L mol⁻¹). UV spectroscopic titrations further confirmed the above results. The interaction between β-biGCD and nucleotides was probed by docking simulation. These results reveal that the biguanidinium moiety mimics the arginine residues of mitochondrial AAC protein.     

Use of the olefin metathesis reaction for highly efficient β-cyclodextrin modification

A series of novel primary face mono-substituted β-cyclodextrin derivatives have been synthesised using the olefin metathesis reaction. Mono-6-allylamino-6-deoxy-β-cyclodextrin easily synthesised by nucleophilic substitution of mono-6-tosyl-β-cyclodextrin is the key synthon in the preparation of cyclodextrin derivatives mono-functionalised at the primary face by alkyl, aryl or perfluoroalkyl groups using Grubbs catalyst. In the cases of vinylbenzene and 1H,1H,2H-perfluoro-1-octene, the metathesis reactions yield with 95% stereoselectivity of the E-isomer.     

Xylose-DNA Containing the Four Natural Bases

Oligonucleotides containing (2′-deoxy-β-D -xylofuranosyl)guanine have been prepared. For this purpose 2-aminoadenosine ( 5 ) was synthesized and converted to 2′-deoxy-β-D -xyloguanosine ( 1 ). The related 2′-deoxy-β-D -xyloisoguanosine ( 3 ) and 2′-deoxy-β-D -xyloxanthosine ( 4 ) were also synthesized. Compound 1 was converted to the phosphonate and phosphoramidite building blocks 10 and 11 , respectively. The oligodeoxynucleotide (5′-3′)d(xG-xT-xA-xG-xA-xA-xT-xT-xC-xT-xA-xC-T) ( 18 ) formed a duplex with the same T_m as the parent (5′-3′)-(G-T-A-G-A-A-T-T-C-T-A-C) ( 19 ), but with an inverted CD spectrum.     

Synthesis of 2′-deoxyribofuranosyl indole nucleosides related to the antibiotics SF-2140 and neosidomycin

The 2′-deoxyribofuranose analog of the naturally occurring antibiotics SF-2140 and neosidomycin were prepared by the direct glycosylation of the sodium salts of the appropriate indole derivatives, with 1-chloro-2- deoxy-3,5-di-O-p-toluoyl-α-D-erythropentofuranose ( 5 ). Thus, treatment of the sodium salt of 4-methoxy-1H- indol-3-ylacetonitrile ( 4a ) with 5 provided the blocked nucleoside, 4-methoxy-1-(2-deoxy-3,5-di-O-p-toluoyl-β- D-erythropentofuranosyl)-1H-indol-3-ylacetonitrile ( 6a ), which was treated with sodium methoxide to yield the SF-2140 analog, 4-methoxy-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indol-3- ylacetonitrile ( 7a ). The neosidomycin analog ( 8 ) was prepared by treatment of the sodium salt of 1H-indol-3-ylacetonitrile ( 4b ) with 5 to obtain the blocked intermediate 1-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythropentofuranosyl) ?1H-indol-3-ylace-tonitrile ( 6b ) followed by sodium methoxide treatment to give 1-(2-deoxy-β-D-erythropentofuranosyl)-1H- indol-3-ylacetonitrile ( 7b ) and finally conversion of the nitrile function of 7b to provide 1-(2-deoxy-β-D- erythropentofuranosyl)-1H-indol-3-ylacetamide ( 8 ). In a similar manner, indole ( 9a ) and several other substituted indoles including 1H-indole-4-carbonitrile ( 9b ), 4-nitro-1H-indole ( 9c ), 4-chloro-1H-indole-2-carboxamide ( 9d ) and 4-chloro-1H-indole-2-carbonitrile ( 9e ) were each glycosylated and deprotected to provide 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole ( 11a ), 1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole-4- carbonitrile ( 11b ), 4-nitro-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-indole ( 11c ), 4-chloro-1-(2-deoxy-β-D- erythropentofuranosyl)-1H-indole-2-carboxamide ( 11d ) and 4-chloro-1-(2-deoxy-β-D-erythropentofuranosyl)- 1H-indole-2-carbonitrile ( 11e ), respectively. The 2′-deoxyadenosine analog in the indole ring system was prepared for the first time by reduction of the nitro group of 11c using palladium on carbon thus providing 4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)- 1H-indole ( 16 , 1,3,7-trideaza-2′-deoxyadenosine).     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.