Sodium Methoxide In Methanol Research Articles

Non-conventional epimerisation and functionalisation of quinic acid and shikimic acid methyl esters

In a convenient one-pot acetalation procedure using chloral/DCC, methyl (-)-quinate and methyl (-)-shikimate were converted into their 4- epi-derivatives containing a carbamoyl function in 3-position and the trichloroethylidene acetal group in 4,5-position. Additionally, an spiro-byproduct, 1R, 3R, 4R, 5R)- 3′-N- cyclohexyl- 3-O-( cyclohexylcarbomyl)- 4,5-O-( 2,2,2-trichloroethylidene)spiro[[cyclohexane-3,4,5-triol-1,5′-[1,3]oxazolidine]]-2′,4′-dione, was formed from methyl (-)-quinate in 10% yield. Decarbamoylation of the compounds is possible by heating in methanolic sodium methoxide.

A Simple Synthesis of 2′,5′-Disubstituted-Spiro [Dihydroacridine 9(10H), 4′-Thiazolines] by the Reaction of Corresponding 3-(Acridin-9-Yl)-Thioureas with Methyl Bromoacetate and Bromoacetonitrile

A convenient method has been devised for the preparation of the spirodihydro-acridinethiazolines 5a-j by the treatment of thioureas 3a-e with methyl bromoacetate and bromoacetonitrile via non-isolable isothioureas 4a-j and their subsequent cyclization with methanolic sodium methoxide.

Ammonia ruthenium complexes for the access to new hydrido, carbonyl and isocyanide ruthenium-alkynyl derivatives

The potential in preparative chemistry of the precursors trans-[Ru(NH 3)(CCR 1)(Ph 2PCH 2CH 2PPh 2) 2]PF 6 ( 3) has been studied. They offer a convenient access, by NH 3 displacement, to new functional alkynyl-ruthenium derivatives. Complexes 3 react with alkynes HCCR 2 to give unsymmetrical trans-Ru(CCR 1)(CCR 2)(dppe) 2 compounds 4a-c, and with sodium methoxide in methanol they open the route to a variety of mixed hydride complexes 5a-c, trans-Ru(H)(CCR 1)(dppe) 2. In contrast, with carbon monoxide or isocyanides CNR 3 (R 3:CH 2Ph, C 6H 11, Me 3C) they allow the preparation of cationic derivatives trans-(Ru(CO)(CCR 1)(dppe) 2]PF 6 ( 6a-c) or trans-[Ru(CNR 3)(CCR 1)(dppe) 2]PF 6 ( 7a-d).

Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio- l- and - d-arabinopyranosides possessing antithrombotic activity

5- S-Benzoyl-2,3- O-isopropylidene-5-thio- l-arabinose, prepared from l-arabinose diethyl dithioacetal gave, on treatment with sodium methoxide in methanol, 4- O-benzoyl-2,3- O-isopropylidene-5-thio- l-arabinopyranose 12 which was converted into its 1- O-acetate 14. Hydrolysis of 12 in acetic acid–water afforded, after acetylation, 1,2,3-tri- O-acetyl-4- O-benzoyl-5-thio- l-arabinopyranose 17 which was transformed into 2,3-di- O-acetyl-4- O-benzoyl-5-thio- l-arabinopyranosyl bromide 20. Zemplén deacylation of 17 gave 5-thio- l-arabinopyranose which was converted via 1,2,3,4-tetra- O-acetyl-5-thio- β- l-arabinopyranose 5 into 2,3,4-tri- O-acetyl-5-thio- β- l-arabinopyranosyl bromide 6 and into O-(2,3,4-tri- O-acetyl-5-thio- l-arabinopyranosyl) trichloro-acetimidate 7. Glycosidation of 4-nitrophenol with 12 under the Mitsunobu conditions afforded 4-nitrophenyl 4- O-benzoyl-2,3- O-isopropylidene-5-thio- α- and β- l-arabinopyranoside in a ∼1:2 ratio. Condensation of the glycosyl donors 6, 7, 17, and 20 with 4-cyano- and 4-nitrobenzenethiol yielded, after deacylation, 4-cyano- and 4-nitrophenyl 1,5-dithio- α- and β- l-arabinopyranosides 28 α, 28 β, 29 α and 29 β in different ratios and yields, depending on the reaction conditions applied. In a similar manner the corresponding d-isomers 30 α, 30 β, 31 α and 31 β were also prepared. All of these glycosides, except 28 α, showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference.

A concise methodology for the stereoselective synthesis of O-glycosylated amino acid building blocks: complete 1H NMR assignments and their application in solid-phase glycopeptide synthesis.

A facile strategy for the stereoselective synthesis of suitably protected O-glycosylated amino acid building blocks, namely, Nalpha-Fmoc-Ser-[Ac4-beta-D-Gal-(1-3)-Ac2-alpha or beta-D-GalN3]-OPfp and Nalpha-Fmoc-Thr-[Ac4-beta-D-Gal-(1-3)-Ac2-alpha or beta-D-GalN3]-OPfp is described. What is new and novel in this report is that Koenigs-Knorr type glycosylation of an aglycon serine/threonine derivative (i.e. Nalpha-Fmoc-Ser-OPfp or Nalpha-Fmoc-Thr-OPfp) with protected beta-D-Gal(1-3)-D-GalN3 synthon mediated by silver salts resulted in only alpha- and/or beta-isomers in excellent yields under two different reaction conditions. The subtle differences in stereoselectivity were demonstrated clearly when glycosylation was carried out using only AgClO4 at -40 degrees C which afforded a-isomer in a quantitative yield (alpha:beta = 5:1). On the other hand, the beta-isomer was formed exclusively when the reaction was performed in the presence of Ag2CO3/AgClO4 at room temperature. A complete assignment of 1H resonances to individual sugar ring protons and the characteristic anomeric alpha-1 H and beta-1 H in Ac4Galbeta(1-3)Ac2GalN3 alpha and/or beta linked to Ser/Thr building blocks was accomplished unequivocally by two-dimensional double-quantum filtered correlated spectroscopy and nuclear Overhauser enhancement and exchange spectroscopy NMR experiments. An unambiguous structural characterization and documentation of chemical shifts, including the coupling constants for all the protons of the aforementioned alpha- and beta-isomers of the O-glycosylated amino acid building blocks carrying protected beta-D-Gal(1-3)-D-GalN3, could serve as a template in elucidating the three-dimensional structure of glycoproteins. The synthetic utility of the building blocks and versatility of the strategy was exemplified in the construction of human salivary mucin (MUC7)-derived, O-linked glycopeptides with varied degrees of glycosylation by solid-phase Fmoc chemistry. Fmoc/tert-butyl-based protecting groups were used for the peptidic moieties in conjunction with acetyl sugar protection. The transformation of the 2-azido group into the acetamido derivative was carried out with thioacetic acid on the polymer-bound glycopeptides before the cleavage step. After cleaving the glycopeptide from the resin, the acetyl groups used for sugar OH-protection were removed with sodium methoxide in methanol. Finally, the glycopeptides were purified by reversed-phase high-performance liquid chromatography and their integrity was confirmed by proton NMR as well as by mass spectral analysis. Secondary structure analysis by circular dichroism of both the glycosylated and nonglycosylated peptides revealed that carbohydrates did not exert any profound structural effect on the peptide backbone conformation.

Comparison of ?G�Acid (gas phase) and kinetic acidities measured in methanolic sodium methoxide

Hydron exchange rates, kexc (M−1s−1), using methanolic sodium methoxide were compared with ΔG°Acid, (kcal mol−1) (gas phase) for 9-phenylfluorene, C6H5CH(CF3)2, m-CF3C6H4CH(CF3)2, p-CF3C6H4CHClCF3, m-CF3C6H4CHClCF3, 3,5-(CF3)2C6H3CHClCF3, fluorene and C6F5H. There is a good linear correlation for p-CF3C6H4CHClCF3, m-CF3C6H4CHClCF3 and 3,5-(CF3)2C6H3CHClCF3, with the others falling off the line. The fluorinated benzyl compounds and pentafluorobenzene have near-unity isotope effects and therefore differ from the fluorenyl compounds. Although the acidity and the exchange rates for three of the compounds [9-phenylfluorene, C6H5CH(CF3)2 and p-CF3C6H4CHClCF3] are similar, the important proton-transfer step to form a hydrogen-bonded carbanion intermediate and the subsequent breaking of that weak bond to form a free carbanion in methanol differ significantly for the fluoernyl compound compared with the two fluorinated benzylic compounds. © 1998 John Wiley & Sons, Ltd.

A carbonyl oxide route to antimalarial yingzhaosu A analogues: Synthesis and antimalarial activity

Ozonolysis of R-carvone and in situ trapping with primary alcohols ROH (R= Me, Et, Bu, Pent, Oct) produces hydroperoxy ketals (5a-e) as a 1:1 mixture of diastereomers. Cyclisation of these intermediates with catalytic sodium methoxide in methanol produces the corresponding endoperoxide derivatives (6a-6e). The pentyl and octyl endoperoxide derivatives demonstrate reasonable antimalarial potency in vitro against the HB3 strain of Plasmodium falciparum. A mechanism for antimalarial action involving the formation of a C-centred radical is proposed.

Comparison of ΔG°Acid (gas phase) and kinetic acidities measured in methanolic sodium methoxide

Comparison of ΔG°Acid (gas phase) and kinetic acidities measured in methanolic sodium methoxide

Comparison of ΔG°Acid (gas phase) and kinetic acidities measured in methanolic sodium methoxide

Comparison of ΔG°Acid (gas phase) and kinetic acidities measured in methanolic sodium methoxide

The synthesis of 3‐[(dimethylamino)(2‐phenyl‐5‐oxo‐2‐oxazolinyl‐idene‐4)methyl]imidazo[1,2‐x]azines and related compounds, intermediates in the formation of azaaplysinopsin derivatives

Abstract4‐(2‐Bromo‐1‐dimethylaminoethylidene)‐2‐phenyl‐5(4H)‐oxazolone (5) reacts with N,N‐dimethyl‐N'‐heteroarylformamidines 7 to form imidazoazine derivatives 9 with the oxazolone ring connected through a conjugated double bond to the fused imidazole system at position 3. Compounds 9 were transformed with sodium methoxide in methanol into 2‐benzoylamino‐3‐dimethylamino‐3‐imidazoazinylpropenoates 10, while by treatment with hydrochloric acid in methanol, 3‐(benzoylaminoacetyl)imidazoazines 12 were formed. The synthesis of compounds 9 represents a facile route to intermediates in the synthesis of azaaplysinopsin and related systems.

A site selective functionalisation of 1,3-bis(trifluoromethyl)benzene

1,3-Bis(trifluoromethyl)benzene was regioselectively metalated and subsequently carboxylated at position 2 to give 2,6-bis(trifluoromethyl)benzoic acid. Treatment of the acid with sulphur tetrafluoride gave 2,6-bis(trifluoromethyl)benzoyl fluoride which was readily converted to 2,6-bis(trifluoromethyl)benzyl alcohol and further to 2,6-bis(trifluoromethyl)benzaldehyde. Bromination of 2,6-bis(trifluoromethyl)benzoic acid with 1,1-dibromo-5,5-dimethylhydantoin proceeded regioselectively affording 4-bromo-2,6-bis(trifluoromethyl)benzoic acid almost quantitavely. The latter was fluorinated to the corresponding acid fluoride which on treatment with methanolic sodium methoxide gave 4-methoxy-2,6-bis(trifluoromethyl)benzoic acid or its methyl ester, depending on the reaction conditions. 4-Methoxy-2,6-bis(trifluoromethyl)benzoic acid, via its acid fluoride, was also transformed, first to the corrsponding benzyl alcohol, then to the benzaldehyde. Lithiation of 4-methoxy-2,6-bis(trifluoromethyl)benzoic acid, followed by methylation, proceeded with low selectivity, nevertheless, methyl 4-methoxy-3-methyl-2,6-bis(trifluoromethyl)benzoate was formed as the main product which was stepwise converted to 4-methoxy-3-methyl-2,6-bis(trifluoromethyl)benzyl alcohol and 4-methoxy-3-methyl-2,6-bis(trifluoromethyl)-benzaldehyde, albeit in low total yield.

An economic synthesis of 1,2,3,4-tetra- O-acetyl-5-thio- d-xylopyranose and its transformation into 4-substituted-phenyl 1,5-dithio- d-xylopyranosides possessing antithrombotic activity

d-Xylose was converted via 1,2- O-isopropylidene- α- d-xylofuranose ( 4) into 3- O-benzoyl-5- S-benzoyl-1,2- O-isopropylidene- α- d-xylofuranose which, after methanolysis, acetylation and subsequent acetolysis afforded 1,2,3,4-tetra- O-acetyl-5-thio- α- d-xylopyranose ( 14) in an overall yield of 36%. Reaction of 4 with thionyl chloride gave a mixture of the diastereomeric cyclic sulfites, the structures of which were established by X-ray crystallography. Their oxidation with sodium periodate afforded the corresponding cyclic sulfate 23. Treatment of 23 with potassium thioacetate gave the potassium salt of 5- S-acetyl-1,2- O-isopropylidene- α- d-xylofuranose 3- O-sulfonic acid ( 26) which, after methanolysis, acetylation and subsequent acetolysis afforded 14 in an overall yield of 56%. Treatment of 4 with sulfuryl chloride gave a mixture containing 5-chloro-3- O-chlorosulfonyl-5-deoxy-1,2- O-isopropylidene- α- d-xylofuranose, 3,7,9,11-tetraoxa-4-thia-10-dimethyl-tricyclo[6,3,0,0 2,6]undecane S-dioxide and 23 in a 2:3:7 ratio. Tetraacetate 14 was converted into the α-1-bromide 18 as well as into the α-1- O-trichloroacetimidate 17. These three compounds were used as donors for the glycosylation with 4-cyanothiophenol, affording the 4-cyanophenyl 2,3,4-tri- O-acetyl-1,5-dithio- α- ( 29) and β- d-xylopyranoside ( 30) in different ratios, depending on the reaction conditions. When donor 18 was used in the presence of potassium carbonate, besides 29 and 30 two aryl C-glycosylated-thioglycosides, i.e. 4-cyano-2-(2,3,4-tri- O-acetyl-5-thio- β- d-xylopyranosyl)phenyl 2,3,4-tri- O-acetyl-1,5-dithio- α- and β- d-xylopyranoside ( 32 and 33) as well as 4-cyano-2-(2,3,4-tri- O-acetyl-5-thio- β- d-xylopyranosyl)phenyl disulfide 34 could be isolated as byproducts. Deacetylation of 30 with sodium methoxide in methanol afforded, besides 4-cyanophenyl 1,5-dithio- β- d-xylopyranoside ( 1), the corresponding 4-[(methoxy)(imino)methyl]phenyl glycoside 2. The 4-cyano group of 1 was converted into the 4-aminothiocarbonyl, the 4-(methylthio)(imino)methyl, the 4-amidino and the 4-(imino)(hydrazino)methyl group. All of these glycosides showed a significant antithrombotic activity on rats.

Synthesis of [ω-3H-MeBmt1]-cyclosporin A

[ 3 H]-Cyclosporin A labeled at the first amino acid ([ω- 3 H-MeBmt 1 ]CS) has been prepared by tritium gas hydrogenolysis of [O-acetyl-ω-bromo-MeBmt 1 ]CS followed by deprotection with methanolic sodium methoxide. The requisite bromo intermediate was prepared by bromination of [O-acetyl-MeBmt 1 ]CS with N-bromosuccinimide. After synthesis and purification, 2.45 mg of [ω 3 H-MeBmt 1 ]CS with a total activity of 327 MBq were produced with a radiochemical purity >97 %, and specific activity of 160 GBq/mmol (4.3 Ci/mmol).

Synthesis of 3′-Azido, 2′,3′-Didehydro, and 3′,4′-Didehydro Nucleosides from 5-Alkoxymethyluracils

Reaction of methyl 5-tert-butyldiphenylsilyl-2,3-dideoxy-3-iodo-D-threo-pentofuranoside (3) with silylated 5-alkoxymethyluracils 2a–c using trimethylsilyl trifluoromethanesulfonate as a catalyst afforded the α nucleosides 4a–c and the β nucleosides 5a–c. The corresponding 3′,4′- and 4′,5′-didehydro nucleosides 6–9 were prepared in an elimination reaction by treating the iodo nucleosides 4a–c or 5a–c with 10 equivalents of sodium methoxide in methanol under reflux. The deprotected 3′-azido nucleosides 10a–c and 11a–c of the AZT type as well as the 4′,5′-didehydro nucleosides 7a–c and 9a–c were prepared by treating 4a–c and 5a–c, respectively, with sodium azide and subsequently with tetrabutylammonium fluoride.

Action of Base on Methyl 6-Thio- (and 6-Deoxy-) 2-O-Methanesulfonyl-α-d-Glucopyranoside Derivatives1

Treatment of methyl 4-O-benzoyl-3-O-tert-butyldiphenylsilyl-2-O-methanesulfonyl-6-thio-α-d-glucopyranoside (8) and its 6-deoxy analogue (11) with methanolic sodium methoxide, afforded methyl 2,3-anhydro-mannopyranoside derivatives as a consequence of an O3 → O4 TBDPS rearrangement. When the protecting group at C-3 was 2-methoxyethoxy methyl ether only deacylation and methanolysis of the methanesulfonyl group occurred.

Synthesis and surface properties of chemodegradable anionic surfactants: Sodium carboxylates of cis‐1,3‐dioxane derivatives

AbstractThe 2‐n‐alkyl‐5‐carboxy‐5‐methyl‐1,3‐dioxanes were obtained in good yield from the reaction of aliphatic aldehydes with 2,2‐bis(hydroxymethyl)propionic acid in dichloromethane solution, catalyzed by p‐toluenesulfonic acid monohydrate. Nuclear magnetic resonance analysis indicated that they were pure cis‐isomers with the axial configuration of the carboxylic group at the C‐5 carbon atom of the 1,3‐dioxane ring. The acids were converted, with retention of the configuration, to their sodium salts by reaction with sodium methoxide or sodium hydroxide in methanol. The physicochemical properties of the acids and sodium salts, as well as their surface properties at the aqueous solution‐air interface, were determined. Critical micelle concentration, surface excess concentration, surface area demand per molecule of sodium salts at the monomolecular surface layer, and standard free energy of micellization were determined based on surface tension measurements.

Synthesis of Some 6-Substituted 5-Azacytidines

Protected 6-substituted benzyl, phenyl and chloromethyl derivatives of 5-azacytidine 8-10 have been prepared by addition of phenylacetyl- (2), benzoyl- (3) or (chloroacetyl)guanidine (4) to 2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate (1) and subsequent silylation-mediated cyclization of the obtained acyl(carbamoyl)guanidines 5-7. 4-Amino-6-phenyl-1,3,5-triazin-2(1H)-one (12) was obtained by condensation of carbamoylguanidine (13) with methyl benzoate in presence of methanolic sodium methoxide or by condensation of 13 with triethyl orthobenzoate in N,N-dimethylformamide. Stannic chloride catalyzed condensation of silylated 6-phenyl derivative 11 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribose (14) in 1,2-dichloroethane afforded a 1.2 : 1 mixture of N1 and N3 nucleosides 9 and 15, respectively. Methanolysis of the protected compounds 8-10 and 15 gave the respective free nucleosides 16-19. The latter compounds inhibited the growth of bacteria E. coli B to a much lower extent than the unsubstituted 5-azacytidine.

Simplified preparation of the ginsenoside-Rh 2 minor saponin from ginseng

Condensation of the 12- O-acetylderivative of 20(S)-protopanaxadiol [dammar-24-ene-3β,12β,20(S)-triol] with tetra- O-acetyl-α- d-glucopyranosyl bromide in the presence of silver oxide in dichloroethane, followed by deprotection with sodium methoxide in methanol, results in formation of the 3- O-β- d-glucopyranosyldammar-24-ene-3β,12β,20(S)-triol identical with natural ginsenoside-Rh 2. The 12- O-acetyl-20(S)-protopanaxadiol is easily prepared from betulafolienetriol via the 3-keto-12- O-acetylderivative followed by NaBH 4 reduction. This comparatively simple five-step synthesis makes this hitherto rare ginsenoside relatively accessible.

Synthesis of 3-halopyrroles

Abstract 3-Chloro-and 3-bromo-2-arylpyrroles, which are potential physiologically active compounds in agrochemistry and pharmaceutical sciences, were efficiently prepared from the corresponding 2-aryl-1-pyrrolines by α,α-dihalogenation with N-halosuccinimides and subsequent base-induced monodehydrohalogenation using sodium methoxide in methanol.

Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives

3',5'-Di-O-benzoyl-4'-C-hydroxymethylthymidine (3) was prepared in four steps from 3'-O-(tert-butyldimethylsilyl)-4'-C-hydroxymethylthymidine (1). Oxidation of 3 with pyridinium dichromate afforded 3',5'-di-O-benzoylthymidine-4'-C-carboxylic acid (4) which on debenzoylation gave free thymidine-4'-C-carboxylic acid, (3R,2S,5R)-3-hydroxy-2-hydroxymethyl-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)tetrahydrofuran-2-carboxylic acid, (5). Esterification of acid 5 with diazomethane afforded the methyl ester 6. Its isopropyl ester 7 was obtained by transesterification of the methyl ester 6. Reaction of ester 6 with ammonia and hydrazine led to the respective amide 8 and hydrazide 9. Upon reaction with 1,1'-carbonyldiimidazole, the protected acid 4 was converted into the corresponding imidazolide 11, which, without isolation, was treated with glycinamide, dimethylamine and aminoethanol to give aminocarbonylmethylamide 12a, N,N-dimethylamide 13a and hydroxyethylamide 14a, respectively. The free amides 12b, 13b and 14b were obtained by methanolysis of corresponding benzoates with methanolic sodium methoxide. Neither of the prepared compounds exhibited significant activity against HIV.