Introduction of a New Class of Ligands for the Metal-Catalyzed Enantioselective Synthesis

Protected thiosugars were prepared as ligands for the metal-catalyzed enantioselective synthesis. The protecting groups in these ligands were varied to test a proposed new concept for the metal-catalyzed enantioselective synthesis. This new concept centres on the use of a stair-like ligand with a large substituent on one side and a small substitutent on the other rather than the commonly employed ligands which have C₂ symmetry (see Fig.3). In such a ligand, both substituents should have a major influence on the coordination of a prochiral substrate. To test this proposal, 3-thio-α-D -glucofuranose derivatives with the following substituents were synthesized: 1,2-O-isopropylidene-5,6-O-methylidene (see 24 ), 1,2:5,6-di-O-isopropylidene (see 2 ), 5,6-O-cyclohexylidene-1,2-O-isopropylidene (see 23 ), 1,2-O-cyclohexylidene-5,6-O-isopropylidene (see 14 ), 1,2:5,6-di-O-cyclohexylidene (see 13 ), 5,6-O-(adamantan-2-ylidene)-1,2-O-isopropylidene (see 21 ), and 1,2:5,6-di-O-(adamantan-2-ylidene) (see 25 , Table 2). As a representative of the allofuranoses, 1,2:5,6-di-O-isopropylidene-3-thio-α-D -allofuranose ( 6 ) was chosen. The following derivatives of 1,2-O-isopropylidene-α-D -xylofuranose were also synthesized: 1,2-O-isopropylidene-5-deoxy-3-thio-α-D -xylofuranose ( 29 ), 1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 28 ) and 5-O-[(tert-butyl)-diphenylsilyl]-1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 15 , see Table 2). The proposed concept was tested using the copper-catalyzed 1,4-addition of BuMgCl to cyclohex-2-en-1-one. The enantioselectivity was very dependent on the ligand used and was up to 58%.     

Esters phosphoriques cycliques ou non cycliques de quelques O-isopropylidène-1,2-α-D-pentofurannoses. Communication préliminaire

Cyclic and acyclic phosphate esters of some 1,2-O-isopropylidene-α-D -pentofuranoses When treated with monophenyl phosphorodichloridate, 1,2-O-isopropylidene-α-D -xylofuranose gave the two possible, isolable isomers of the corresponding 3,5-cylic phenylphosphate. Upon phosphorylation of the same sugar derivative using bis (2,2,2-trichloroethyl) phosphorochloridate only one isomer was formed. The same situation obtained when preparing 1,2-O-isopropylidene-α-D -ribofuranose-3,5-cyclic phenylphosphate. The synthesis of a new kind of sugar phosphate with a branched-chain unsaturated sugar moiety namely the trans-3-deoxy-3-C-cyanomethylene-1,2-O-isopropylidene-D -erytho-pentofuranose 5-bis(2,2,2-trichloroethyl) phosphate is also described.     

Dérivés C-Glycosyliques XXXII. Synthèse de dérivés spiro-C-glycosylidéniques par cyclisation nucléophile. Communication préliminaire

C -Glycosylic derivatives XXXII. Synthesis of spiro-C -glycosylidenic derivatives via nucleophilic cyclization. On treatment with compounds bearing two nucleophilic groups as ethylenediamine, o-phenylenediamine or their monooxa or monothia analogues, 1,2:5, 6-di-O-isopropylidene-α-D -ribo-hexofuranos-3-ulose gave with excellent yields the corresponding spiro-C-glycosylidenic derivative; for example, when using o-phenylenediamine, a spirobenzimidazoline ( 5 ) was obtained. The latter compound underwent, on oxidation, a ring expansion to a morpholinobenzimidazole ( 8 ). Spirobenzodiazepines, spirobenzooxazepines and spirobenzothiazepines were formed when applying the same type of cyclization reaction to 3-C-acetylmethylene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D -ribo- and α-D -xylo-hexofuranoses.     

Synthesis of 1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-Mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose

1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose were synthesized.     

Etude par spectrométrie de masse de la fragmentation du désoxy-3-di-O-isopropylidène-1,2: 5,6-méthylidène-3-α-D-hexofurannose et de quelques analogues substitués en C(3′)

Electron Impact Mass Spectrometry of the 3-Desoxy-1,2: 5,6-di-O-isopropylidene-3-methylidene-δ-D -hexofuranose and Some C(3′)-Substituted Analogues The mass spectra of the 3-desoxy-1,2:5, 6-di-O-isopropylidene-3-methylidene- α-D -ribo-hexofuranose and of some C(3′)-mono- and -disubstituted derivatives have been investigated. Deuterium labelled molecules allow fragmentation modes to be proposed.     

Synthesis of 3-Deoxy-3-C-Trifluoromethyl-d-Ribose From d-Xylose or d-Glucose

Abstract

The synthesis of 3-deoxy-1,2,O-isopropylidene-3-C-trifluoromethyl-α-D-ribofuranose is described. After a first approach from a commercial D-xylose derivative which was limited by an incomplete stereoselectivity, the synthesis of the title compound was performed from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose by a reaction sequence where key steps: trifluoromethylation with CF₃SiMe₃ and radical deoxygenation are highly stereoselective.     

Chemical studies of carbohydrates. Part I. Conversion of derivatives of glucose and allose into pyrazoles and pyridazines

On reaction of 1,2:5,6-di-O-isopropylidenc-3-O-(p-tolylsulfonyl)-α-D-glueofuranose ( 1 ) with hydrazine hydrate at 140° besides formation of 3-deoxy-3-hydrazino-1,2:5,6-di-O-isopropylidene-α-D-allofuranose ( 2 ) and 3-dcoxy-1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose ( 3 ), ring transformation into 3-[4′-(2′,2′-dimethyl-1′,3′-dioxolanyl)]pyridazine ( 4 ) takes place. At 170°, however, only 2 and 4 are formed, indicating that 3 is the precursor of 4. Treatment of 3 with hydrazine hydrate at 170° indeed gives a nearly quantitative ring expansion into 4. Treatment of 3-dcoxy-3-hydrazino-1,2:5,6-di-O-isopropylidenc-α-D-glucofuranose ( 8 ) as well as the stereoisomeric allofuranose 2 with concentrated hydrochloric acid gives a nearly quantitative ring interconversion into 3-(D-erythro-trihydroxypropyl)pyrazole ( 9 ).     

Synthesis and characterization of some heterocyclic derivatives from 1,2:3,4-Di-o-isopropylidene-α-d-galacto-1,6-hexadialdo-1,5-pyranose oxime

We report the synthesis of 5-[5′-(1′,2′:3′,4′-di-O-isopropylidene-β-L-arabinopyranosyl)]tetrazole, from 1,2:3,4-di-O-isopropylidene-α-D-galacto-1,6-hexodialdo-1,5-pyranose oxime via 1,2:3,4-di-O-isopropylidene-α-D-galcturononitrile as intermediate by 1,3-dipolar cycloaddition. We also report the synthesis of 5-methyl- and 5-phenyl-2-[5′-(1′,2′:3′,4′-di-O-isopropylidene-β-L-arabinopyranosyl)]-1,3,4-oxadiazole from the tetrazole derivative. The physical and spectroscopic characterizations of the heterocyclic derivatives as well as the intermedi ate nitrile and the principal by product are described and we discuss its possible formation pathway. We present the preferential conformation in solution using computational calculation and spectroscopic data.     

Etude en spectrometrie de masse de la fragmentation de di-O-isopropylidene-1,2-5,6-α-D-hexofurannoses

The mass spectra of three stereoisomeric 1,2-5,6-di-O-isopropylidene-α-D -hexofuranoses have been investigated. Fragmentation mechanisms based upon the results which were obtained with deuterium labelled molecules are proposed.     

Synthesis of some 6-S-heterocyclic derivatives of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose

We applied nucleophilic substitution to 6-O-tosyl-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose using sulphur nucleophiles and obtained 6-S-derivatives of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose. We present the physical and spectroscopic characterization of these heterocyclic compounds as well as other related compounds obtained by substitution, using other substrates. The conformational studies of all products are presented and discussed.     

Un nouvel analogue synthétique de l'adénosine: La désoxy-3′-C-dibromométhylidène-3′-adénosine

A novel synthetic analog of adenosine: the 3′-deoxy-3′-C-dibromomenthylidene-adenosine The title compound ( 7 ) has been prepared by a sequence of classical synthetic steps from 3-deoxy-3-C-dibromomethylidene-1,2: 5,6-di-O-isopropylidene-α-D -ribo-hexofuranose ( 1 ). The β-configuration of the nucleoside was established by formation of a cyclonucleoside. 7 is very slowly deaminated by adenosine deaminase. In contrast with its dichloro analog, it does not inhibit the growth of Escherichia coli.     

Chemical studies of carbohydrates (II) On the mechanism of the conversion of a glucose derivative into a pyridazine compound

The formation of 3-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)pyridazine ( 4 ) by reacting 1,2:5,6-di-O-isopropylidene-3-O-(p-tolylsulfonyl)-α-D-glucofuranose ( 1 ) with hydrazine hydrate via the intermediate 3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose ( 3 ) is explained by a mechanism, involving an initial attack of the hydrazine molecule at position 4 in compound 3 , a subsequent ring opening by fission of the C₄? O bond and a ring closure by formation of a N? C₁ bond.     

Synthesis of New Five Membered Nitrogen Containing Heterocycles Bearing D-Galactose Side Chains

The synthesis of 5-[6′-deoxy-(1′,2′:3′,4′-di-O-isopropylidene-α-D-galactopyranos-6′-yl)]tetrazole and its reaction with acetic anhydride and 1,2:3,4-di-O-isopropylidene-6-O-(4-toluenesulfonyl)-α-D-galactopyranose are described.     

Synthesis of Ether-Linked Di- and Trisaccharide Derivatives Part II- Functionalization and Potential Applications of Ether-Linked Di- and Trisaccharides Containing d-Glucose

Abstract

We have prepared three series of functionalized disaccharides of the type A(6→n)B and a trisaccharide with the formula A-O-B-O-C, in which A = D-glucose (or its derivatives) and both B and C are any of D-fructose, D-galactose, D-glucose, xylitol and glycerol (or their derivatives). These compounds resulted from the regiospecific functionalization of either A or B and either the partial or total deprotection of either 6-O-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)-3-O-alkyl-1,2-O-isopropylidene-α-D-glucofuranose or its analogues of type 1 described in part I.¹ We also report results on surface activity and biological properties of some of the molecules prepared.     

Synthesis of 1,2:5,6-Di-O-isopropylidene-3-O-[3-(5-fluorouracil-1-yl)-propionoyi]-α-D-glucofuranose and its antitumor activity

In order to provide a less toxic 5-fluorouracil derivative, 1,2:5,6-di-O-isopropylidene-3-O-[3-(5-fluorouracill-yl)-propionoyl]-α-D-glucofuranose, which was the derivative of 5-fluorouracil combining indirectly to 3-position of diacetoneglucose, was synthesized, and its antitumor activity was tested.     

Synthesis of novel macrocyclic crown ethers from D-glucose

A simple and efficient synthetic protocol for an easy access of carbohydrate-linked crown ethers from cheap and readily available D-glucose in good yields has been devised. The base-mediated cyclization of sugar-linked bis-iodo podands in CH₃CN with amines, including ethylamine and furfurylamine afforded the novel chiral monoaza-15-crown-5-type macrocyclic crown ethers anellated to 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose and 3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose. The glucose-based crown ethers have been characterized by spectroscopy techniques including IR, ¹H NMR, and ¹³C NMR.     

Un nouvel exemple de nucléoside à sucre ramifié insaturé: la désoxy-3′-méthylidène-3′-adénosine

A Novel Example of Unsaturated Branched-chain Sugar Nucleoside: 3′-Deoxy-3′-methylidene-adenosine Starting from 5-O-benzoyl-3-C-methylidene-3-deoxy-1,2-O-isopropylidene-α-D -erythro-pentofuranose ( 11 ) the title compound 8 has been prepared. Its α-anomer ( 9 ) and the acyclic sugar nucleoside 10 have been obtained as by-products. Adenosine deaminase slowly deaminated 8, 9 being not affected. Compound 8 exhibited no antiviral activity, whereas one of its saturated analogues ( 13 ) inhibited the multiplication of the herpes-1 (HF) virus.     

Large scale synthesis of the acetonides of l-glucuronolactone and of l-glucose: easy access to l-sugar chirons

1,2-O-Isopropylidene-α-l-glucurono-3,6-lactone may be synthesized on a 100-200 g scale from cheaply available d-glucoheptonolactone in an overall yield of 94% in four steps via l-glucuronolactone. Subsequent elaboration to l-glucose, diacetone-l-glucose (1,2:5,6-di-O-isopropylidene-α-l-glucofuranose), and monoacetone-l-glucose (1,2-O-isopropylidene-α-l-glucofuranose) allows easy access to a range of l-sugar chirons.     

Analogues de la lincomycine. I. Allongement de la chaîne du di-O-isopropylidène-1,2:3,4-α-D-galacto-hexodialdopyrannose-1,5

Lincomycin analogues. I. Chain-extensions of [1,2:3,4]-di-O-isopropylidene-α-D -galacto-hexodialdo-1,5-pyranose The title aldehydosugar 1 treated with Wittig reagents led in good to excellent yields to the unsaturated sugar derivatives 3–7 and 10–15, 8 having been prepared by condensation of 1 with malonic acid. The configuration (Z or E) of each compound obtained has been established by ¹H-NMR. These chain-extensions constitute the first synthetic step towards the preparation of lincomycin analogues.     

Nouveaux types de sucres acétyléniques. Communication préliminaire

Novel types of acetylenic sugars The coupling, following Cadiot's procedure, of a 6-bromo-5,6-dideoxy-1,2-O-isopropylidène-3-O-methyl-α-D -xylo-hex-5-yno-1, 4-furanose (1) with phenylacetylene, 2-propyn-1-ol or terminal acetylenic sugars gave with excellent yields the expected diynes (an enediyne when the terminal acetylene was the 3,5, 6-trideoxy-1,2-O-isopropylidene-α-D -glycero-hex-3-en-5-yno-1,4-furanose 7 ). The chloro analogue 8 of 1 on treatment with lithium thiophenate gave the corresponding phenylthio-acetylenic sugar 9 . An acetylene was also formed by reacting the gem-difluoro-olefinic sugar 10 with butyllithium whereas the same olefinic sugar and its 3-O-benzyl analogue 11 gave only a gem-fluoro-arylthio-olefinic sugar (13–15) as a mixture of the Z and E isomers (Z/E > 4) when treated with the conjugate base of an arylmercaptan.