On Resin Modification of Monosaccharides

Ellman's dihydropyran resin was used for selective protection of monosaccharide thioglycosides and glycosides. Following on‐resin acylation and subsequent cleavage of the polymer‐bound intermediates, product components having selectively unblocked hydroxyl functions could be obtained.      

Galactose‐Phosphonates as Mimetics of the Sialyltransfer by Trypanosomal Sialidases

In an attempt to find competitive inhibitors of the trans‐sialidase of the pathogen Trypanosoma cruzi, we have synthesized conjugates of carbocyclic sialylmimetics (e.g., cyclohexenephosphonates) and galactose derivatives. A trans‐sialidase inhibition assay revealed an interesting preference for ethylidene‐spacered conjugates involving the 3‐position of the sugar.      

Highly Efficient α‐Sialylation by Virtue of Fixed Dipole Effects of N‐Phthalyl Group: Application to Continuous Flow Synthesis of α(2‐3)‐and α(2‐6)‐Neu5Ac‐Gal Motifs by Microreactor

Highly α‐selective sialylation of sialic acid N‐phenyltrifluoroacetimidate with various galactose and lactose acceptors has been achieved by introducing the C‐5 N‐phthalyl group on the donor. The “fixed dipole effect” of the N‐phthalyl group was proposed to explain the high reactivity and α‐selectivity. The microfluidic system was applied to the present α‐sialylation, which is amenable to large‐scale synthesis. The N‐phthalyl group was removed by treatment with methylhydrazine acetate, for which protocol can be readily applied to the synthesis of a variety of sialic acid‐containing oligosaccharides.      

MAOS of D‐Gluconic Acid,D‐Glucono‐1,4‐ and 1,5‐Lactones,Esters, Hydrazides,and Benzimidazoles Thereof

Microwave‐assisted organic synthesis (MAOS) of D‐gluconic acid can be efficiently done by oxidation of D‐glucose with bromine water, upon irradiation with microwave (MW). It was also used for the conversion of D‐gluconic acid to ethyl D‐gluconate, D‐glucono‐1,4‐ and 1,5‐lactones, gluconyl hydrazide, and gluconyl phenylhydrazide in yields comparable to those obtained by conventional methods, but in much shorter times. A convenient microwave‐mediated condensation of D‐gluconic acid with o‐phenylenediamines provided the respective acyclonucleoside benzimidazole in short time and good yield.      

Synthesis of 2,3‐Dihydroxy‐1‐Epilupinine

The 1,3‐dipolar cycloaddition of unsaturated D‐threo‐hexaldonolactone 3 and a six‐membered cyclic nitrone 11 led to a single adduct 15, which could be transformed into (1S, 2S, 3S, 9aS)‐2,3‐dihydroxy‐1‐hydroxymethyl‐quinolizidine 28 related to epilupinine via a reaction sequence involving rearrangement of the six‐membered lactone ring into a five‐membered one, removal of the terminal carbon atom from the sugar chain, cleavage of the N‐O bond, and the intramolecular alkylation of the nitrogen atom.      

Solid‐Phase Synthesis of Sialyl Tn Antigen

Solid‐phase synthesis of sialyl Tn [α‐Neu5Ac‐(2→6)‐α‐GalNAc‐(1→O)‐Ser] antigen with Kenner's acylsulfonamide linker is described. The acylsulfonamide bond was found to be stable under glycosylation reactions using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter and basic conditions used for the removal of protecting groups. The solid‐phase reaction was monitored by the inverse gated decoupling ¹³C NMR technique, which enabled quantitative analysis of the reaction progress. At the end of the synthesis, the sulfamyl group of the linker was activated by treatment with (trimethylsilyl)diazomethane to provide a N‐methyl‐N‐acylsulfonamide. The acyl group was displaced with hydroxide to give the corresponding precursors of sialyl Tn antigen and its anomeric isomers, which were deprotected to afford the target molecules.      

Synthetic Studies of N‐demethylossamine and Elaboration of its Glycosylation

An amino‐sugar, N‐demethylossamine, was efficiently synthesized from D‐threonine, two stereogenic centers of which were directly used as those at the C‐4 and 5 positions of the target sugar. In addition, the glycosylation study indicated that reaction of the acetate 7 with cyclopentanol under Lewis acid conditions, provided the desired α‐L‐glycoside 9α.      

Lanthanum Trifluoromethane-sulfonate‐Catalyzed Facile Synthesis of Per‐O‐acetylated Sugars and Their One‐Pot Conversion to S‐Aryl and O‐Alkyl/Aryl Glycosides†

Lanthanum trifluoromethanesulfonate‐catalyzed solvent‐free per‐O‐acetylation with stoichiometric acetic anhydride proceeds in high yield (95%–99%) to afford exclusively pyranose products as anomeric mixtures. Subsequent anomeric substitution employing borontrifluoride etherate and thiols or alcohols furnished the corresponding 1,2‐trans‐linked thioglycosides and O‐glycosides, respectively, in good to excellent overall yield (75%–85%). Alternatively, reaction of free sugars in neat alcohol employing the same catalyst at elevated temperature gives the corresponding 1,2‐cis‐linked O‐glycosides (along with 1,2‐trans‐linked glycosides as minor product) in good yield (73%–80%). Anomeric mixtures of compounds thus produced were characterized as their per‐O‐acetylated derivatives.      

Divergent Synthesis of All Possible Optically Active Regioisomers of Myo‐Inositol Mono‐ and Bisphosphates

All possible optically active regioisomers of myo‐inositol mono‐ and bisphosphates were synthesized using inositol derivatives suitably protected with various protecting groups (IR_ns) as key intermediates. A series of procedures including Novozym 435 catalyzed enzymatic resolution of (3aR,4S,7S,7aR)‐rel‐3a,4,7,7a‐tetrahydro‐2,2‐dimethyl‐1,3‐benzodioxole‐4,7‐diol diacetate, several protection and deprotection reactions, and acyl migration afforded two enantiomeric pairs of IR₅ and six enantiomeric pairs of IR₄. Phosphorylation of these key intermediates by the phosphitylation and oxidation procedure gave the target products after removal of the protecting groups.      

Synthesis and Crystallographic Study of1,6‐bis‐(N‐phenothiazinyl)‐2,4‐hexadiyne

1,6‐bis‐(N‐phenothiazinyl)‐2,4‐hexadiyne (I) was synthesized in high yield by oxidative coupling of N‐propargyl phenothiazine. Grown from methylene chloride‐hexane solution, I is a monoclinic crystal, space group C2/c a=14.9500(18) Å; b=13.5512(15) Å; c=12.0116(10) Å; β=102.628(9)° Å; V=2374.6(4) ų. The intermolecular distances and arrangement of I in the unit cell preclude the usual diacetylene reactivity. Nevertheless, heating of I at 145°C results in decomposition of I to phenothiazine and a dark brown solid. In addition, cation‐radicals of I were prepared by oxidation with nitrosonium tetrafluoroborate and iodine to give stable ion‐radical salts.     

REDUCTION OF N -2-SUBSTITUTED BENZIMIDAZOYL IMIDATES

ABSTRACT>

Cathodic reduction of several iminoesters ( 1 ) and ( 2 ) has been investigated by cyclic voltammetry and controlled potential electrolysis at mercury electrode in aprotic DMF, leading to the formation of two reduction steps. The appropriate choice of the nature of R² groups allowed the reductive cyclisation when R² is an ethoxy (or alkoxy) group.

Synthesis of O‐β‐D‐Glucopyranosides of 7‐Hydroxy‐3‐(imidazol‐2‐yl)‐4H‐chromen‐4‐ones

The 7‐hydroxy‐3‐formyl‐4H‐chromen‐4‐one 1 reacted with various cyclic 1,2‐dicarbonyl compounds in the presence of ammonium acetate to furnish 7‐hydroxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 2a–f, which on glucosylation with α‐acetobromoglucose affords 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 3a–f. 7‐O‐β‐D‐Glucopyranosyloxy‐3‐([4,5‐fused] imidazol‐2‐yl)‐4H‐chromen‐4‐ones 4a–f were prepared by deacetylation with anhydrous zinc acetate in absolute methanol. The structure of these new O‐β‐D‐glucosides was established on the basis of chemical, elemental, and spectral analysis. These compounds were evaluated for their in vitro biological activity.

     

Synthesis and Properties of Surfactants derived from N‐Acetyl‐D‐Glucosamine

The synthesis of 2‐acetamido‐2‐deoxy‐6‐O‐octanoyl‐D‐glucono‐1,5‐lactone 9 and 2‐acetamido‐2‐deoxy‐6‐O‐octanoyl‐α‐D‐glucopyranose 7 from 2‐acetamido‐2‐deoxy‐α‐D‐glucopyranose is reported. For both targets, the key intermediate was allyl 2‐acetamido‐3,4‐di‐O‐benzyl‐2‐deoxy‐6‐O‐octanoyl‐α‐D‐glucopyranoside 5. Surface tension measurements (critical micellar concentration of 22.3 mM and 5 mM for 9 and 7, respectively) showed up the surface activity of both compounds, while enzyme inhibition assays indicated that 9 could inhibit bovine β‐N‐acetylglucosaminidase (K_i=6.5 µM) but not Serratia marcescens chitobiase nor hen egg‐white lysozyme. Moreover, 7 was shown to induce chitinase production of S. marcescens and to be readily metabolized by these bacteria.      

Versatile Sugar Derivatives for the Synthesis of Potential Degradable Hydrophilic‐Hydrophobic Polyurethanes and Polyureas

Biodegradable polymers obtained from renewable natural sources are currently receiving increasing attention because they are an alternative to the traditional petroleum‐based plastics. In the present communication we describe the synthesis of the diol monomers 2,3,4‐tri‐O‐benzyl‐L‐arabinitol (ABnOH) and 2,3,4‐tri‐O‐benzylxylitol (XBnOH), and the diamino monomers 1,5‐diamino‐1,5‐dideoxy‐2,3,4‐tri‐O‐benzyl‐L‐arabinitol (ABnNH ₂ ) and 1,5‐diamino‐1,5‐dideoxy‐2,3,4‐tri‐O‐benzylxylitol (XBnNH ₂ ), which can be used in the preparation of new potentially biodegradable sugar‐based polymers. As an example, we describe the synthesis and characterization of a polyurethane [PU‐(ABnOH‐HMDI)] and a polyurea [PUR‐(ABnNH₂‐HMDI)] by poly addition reaction of ABnOH and ABnNH ₂ with 1,6‐hexamethylene diisocyanate.      

MAOS of Sugar Phenylosazones and their Derived Pyrazoles and Triazoles

Microwave‐assisted organic synthesis (MAOS) has proven to be practical to provide heterocycles from sugar osazones; an efficient method was developed for the characterization of sugars via their osazones 1–4 using microwave irradiation. The microwave‐assisted organic synthesis irradiation technique has been applied to convert d‐arabino‐hexose phenylosazone to 2‐phenyl‐4‐(d‐arabinotetrahydroxybutyl‐1,2,3‐triazole (5), which was then oxidized to the corresponding aldehyde whose oxime 9 was transformed to 4‐cyano‐2‐phenyltriazole 10. The condensation of 7 with thiosemicarbozide gave 10. Degradation of 1 afforded mesoxaldehyde 1,2‐bisphenylhydrazone 11, which cyclized to 1‐phenyl‐4‐phenylazo‐pyrazole (12) under acidic conditions. Irradiation of 6 in HBr/AcOH afforded 4‐(d‐arabino‐2′,3′‐di‐O‐acetyl‐1′,4′‐dibromobutyl)‐2‐phenyl‐2H‐1,2,3‐triazole. The acetylated phenylosazone was converted to furopyridazine 14. The irradiation of phenylosazone with acetic anhydride in pyridine gave the respective O‐acetyl derivative, whereas with boiling acetic anhydride gave the pyrazole 14, which afforded 15 and 16.      

Synthesis of 3‐Methoxyoxetane δ‐Amino Acids with D‐lyxo,D‐ribo,and D‐arabino Configurations

Starting from 1,2‐isopropylidene‐d‐xylose (1), 3‐methoxyoxetane δ‐amino acids with d‐lyxo, d‐ribo, and d‐arabino configurations were synthesized. The early introduction of an azide function at C‐5 of 1 shortened the synthetic pathway. Ring contraction of the intermediate d‐xylono‐1,4‐lactone 6 via triflation and treatment with base led to the corresponding 3‐methoxyoxetane δ‐amino ester with d‐lyxo configuration 7. The analogous procedure for d‐ribono‐1,4‐lactone 16 furnished a mixture of d‐ribo and d‐arabino esters 17 and 18. Hydrolysis of the methyl esters 7, 17, and 18 to their corresponding δ‐amino acids was successful with LiOH in THF, in contrast to that of their 3‐hydroxy analog 11.