Synthesis of D-Fructofuranosides Using Phenyl Thioglycosides as Glycosyl Donors

INTRoDUCTlOND-fructofuranosidesarefoundinnatUrinbacterialpolysaccharidesandinplantpolysaccharides1.InsynIhesiningstrUctUresfromatheditionalChineseherbalmedicine,therootoftheAchyranthesbidentataBlume,WhichhastheabilnytoremovebloodStaSisbypromotingbloodcirculation,invigoratetheliverandkidney,Strengthenthetendonsandbones,andcurenUInbnessofthewaistandknee,'welookedforadepeglycosylationmethods.SynthesesofD-fructofuranosidesusingfructofuranosyldonorsarenotveryfrequent;e.g.,mostsynthesesofsu…     

α‐Chlorination of Acetophenones Using 1,3‐Dichloro‐5,5‐Dimethylhydantoin

A novel method for the synthesis of α‐chloroacetophenones using 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) and p‐toluenesulfonic acid in methanol at 30–35°C is described. Substituted acetophenones at the para position or meta position of aromatic ring give α‐chloroacetophenones in high yield. However, reaction of o‐nitroacetophenone does not take place under the same condition.     

A Highly Stereoselective Synthesis of N-Alkyl(2-deoxy-β-D-arabino-hexopyranosyl)amines Via 2-Deoxyglycosyl Phosphorodithioates as Glycosyl Donors

Abstract

This work demonstrates a new application of 2-deoxy-α-D-glycosyl phosphorodithioates 1 as glycosyl donors in the synthesis of N-alkyl-(2-deoxy-D-arabino-hexopyranosyl)amines 3. The reaction of 1 with amines 2 proceeds with high β-stereoselectivity, at ambient temperature, in almost quantitative yield.     

C2-Cyanomethyl (CNMe) Ether-Protected Glycosyl Trichloroacetimidate Donors for Stereoselective β-O-Glycosylations

Stereoselective construction of glycosidic linkages have emerged as one of the pivotal aspects for the synthesis of complex oligosaccharide assemblies. We herein report C2-cyanomethyl (CNMe) ether as a strong stereodirecting group on trichloroacetimidate glycosyl donors for the synthesis of 1,2-trans-β-O-glycosides. The developed donors bearing various arming and disarming protections along with C2-CNMe ether delivered the glycosides in short reaction time, moderate to good yields and high to excellent stereoselectivities. Gluco- and galacto- configured donors were found compatible with an array of alcohols having varied reactivities. The orthogonality of the CNMe ether protection with silyl ether group has been further explored for sequential glycosylations.     

Do Glycosyl Sulfonium Ions Engage in Neighbouring‐Group Participation? A Study of Oxathiane Glycosyl Donors and the Basis for their Stereoselectivity

Neighbouring‐group participation has long been used to control the synthesis of 1,2‐trans‐glycosides. More recently there has been a growing interest in the development of similar strategies for the synthesis of 1,2‐cis‐glycosides, in particular the use of auxiliary groups that generate sulfonium ion intermediates. However, there has been some debate over the role of sulfonium ion intermediates in these reactions: do sulfonium ions actually engage in neighbouring‐group participation, or are they a resting state of the system prior to reaction through an oxacarbenium ion intermediate? Herein, we describe the reactivities and stereoselectivities of a family of bicyclic thioglycosides in which an oxathiane ring is fused to the sugar to form a trans‐decalin‐like structure. A methyl sulfonium ion derived from one such glycosyl donor is so stable that it can be crystallised from ethanol, yet it reacts with complete stereoselectivity at high temperature. The importance of a ketal group in the oxathiane ring for maintaining this high stereoselectivity is investigated using a combination of experiment and ab initio calculations. The data are discussed in terms of S_N1 and S_N2 type mechanisms. Trends in stereoselectivity across a series of compounds are more consistent with selective addition to oxacarbenium ions rather than a shift between S_N1 and S_N2 mechanisms.     

Synthesis of C‐Glycosyl Phosphate and Phosphonate,Analogues of N‐Acetyl‐α‐d‐Glucosamine 1‐Phosphate

Synthesis of α‐C‐ethylene phosphate and phosphonate as well as α‐C‐methylene phosphate analogues of N‐acetyl‐α‐d‐glucosamine 1‐phosphate is reported starting from the common perbenzylated 2‐acetamido‐2‐deoxy‐α‐C‐allyl glucoside. Anomerisation of the corresponding amino α‐C‐glucosyl aldehyde to the β‐aldehyde was observed. Thus, both amino α‐ and β‐C‐glucosyl methanol were obtained after reduction.     

N‐Glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea Derivatives: Potential Anti‐TB Therapeutic Agents

Thiocarlide (THC; N,N′‐bis[p‐(isoamyloxy)phenyl]‐thiourea; also known as Isoxyl^®) has been used in the past as an anti‐tuberculosis agent. In an effort to improve the therapeutic value of THC, several N‐glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea derivatives were synthesized by coupling an aniline derivative and glycosyl isothiocyanates. The minimum inhibitory concentration (MIC) values of the new products against M. tuberculosis were determined.     

Large‐scale Synthesis of Per‐O‐acetylated Saccharides and Their Sequential Transformation to Glycosyl Bromides and Thioglycosides

This work describes a large‐scale synthesis of per‐O‐acetylated mono‐ and disaccharides using a stoichiometric amount of acetic anhydride in the presence of LiClO₄ under solvent‐free conditions. The peracetylated saccharides underwent subsequent anomeric bromination and thioglycosidation in one‐pot to yield synthetically valuable building blocks.     

Reductive Amination of Glycosyl Aldoses: Synthesis of N‐Glycosylated β‐Glycosyl Amino Alcohols and their Enzyme Inhibitory Effect

Abstract

Reductive amination of glycosyl aldehydes (1a–c, 2) with glycosyl amino esters (3a–c, 4) in the presence of sodium borohydride gave diglycosylated amino esters (5–15) in good yield. N‐Glycosyl‐glycosylated amino esters were reduced to the respective diglycosyl amino alcohols (16–26) with LiAlH₄ in good yield. All the synthesized compounds were studied for their inhibitory effect, if any, against hepatic glucose‐6‐phosphatase, glycogen phosphorylase, and intestinal brush border membrane α‐glucosidase; among these compounds 7, 21, and 25 have shown marked inhibition on these enzymes, respectively.     

Preparation of 2‐Amino‐1,3‐butadienes as N‐Pyridine Derivatives

2‐Amino‐1,3‐butadienes as pyridine derivatives have been prepared from corresponding dihydrothiazolo[3,2‐a]pyridinium salts in reactions with a strong base. The pyridinium salts were prepared from pyridine‐2(1H)‐thiones and trans‐1,4‐dibromo‐2‐butene by a vicinal and chemoselective formation of 3‐vinyldihydrothiazolo[3,2‐a]pyridinium salts. A strong base was used for selective proton removal from the vinyl‐substituted 3‐position. A subsequent ring opening provided 2‐substituted 1,3‐butadienes with the azine appended at the annular nitrogen. Simple S‐alkylation yielded a corresponding azinium salt, thereby introducing electrophilic character to the 1,3‐butadiene system. Hydrolysis of the sulfide function provided the corresponding pyridin-2(1H)‐one attached to the 1,3‐butadiene in the 2‐position.     

A Practical One‐Pot Synthesis of New S‐Glycosyl Amino Acid Building Blocks for Combinatorial Neoglycopeptide Synthesis

S‐Glycosyl L‐aspartic acid building blocks were synthesized starting from 1‐thiosugars by reaction with 5‐aminopentanol and suitably protected L‐aspartic acid pentafluorophenyl ester in a one‐pot procedure under Mitsunobu conditions using 1,1′‐azodicarbonyl dipiperidine and trimethyl phosphine. The method allowed for the preparation of S‐glycosyl amino acid building blocks in one step without protection of the amino function for the Mitsunobu condensation. Alternatively, the title compounds were prepared by a stepwise approach via 5‐aminopentyl 1‐thioglycosides.     

An Exceptionally Simple Chemical Synthesis of O‐Glycosylated d‐Glucosamine Derivatives by Heyns Rearrangement of the Corresponding O‐Glycosyl Fructoses

2‐N‐Acetyl‐4‐O‐(β‐d‐galactopyranosyl)‐d‐glucosamine (N‐acetyl‐d‐lactosamine), a very important building block of biologically relevant oligosaccharides such as sialyl Lewis^x, is easily accessible via the Heyns rearrangement of the corresponding O‐glycosylated ketohexose, d‐lactulose. This approach can also be extended to other glucosamine derivatives employing suitable O‐glycosylated ketoses many of which are commercially available. For example, nigerosamine (3‐O‐α‐d‐glucopyranosyl‐d‐glucosamine) was prepared from turanose (3‐O‐α‐d‐glucopyranosyl‐d‐fructose). In combination with a recently introduced vinylogous amide type N‐protecting group, [1,3‐dimethyl‐2, 4, 6 (1H, 3H, 5H)‐trioxopyrimidine‐5‐ylidene] methyl (DTPM), this access is clearly superior to other routes and eminently suitable for scaling up.     

Per-O-Benzylated Ethyl 5-N-Acetyl-α-thiosialoside as a Glycosyl Donor for α-Silylation

Abstract

Per-O-benzylated ethyl 5-N-acetyl-α-thiosialoside 1 was synthesized and its reactivity as a sialyl donor was investigated. It was demonstrated that the reactions of 1 with various primary and secondary alcohol acceptors, including monosaccharides, gave good to excellent yields (53-92%) and acceptable to excellent α-selectivity (α:β?=?2?～?10:1) , showing its promise for application to sialoglycan synthesis.     

High Sensitive and Selective Spectrophotometric Determination of Aluminium after Collection on a Membrane Filter Using 2,3‐Dichloro‐6‐(3‐carboxy‐2‐hydroxy‐1‐naphthylazo)quinoxaline and Zephiramine

Abstract

A high sensitive and selective spectrophotometric method for the determination of aluminium(III) using 2,3‐dichloro‐6‐(3‐carboxy‐2‐hydroxy‐1‐naphthylazo)quinoxaline (DCHNAQ) and zephiramine (zeph) is described. The formed ion pair precipitate between zephiramine and perchlorate ions is effective for the enrichment of aluminium(III) on a membrane filter as its ternary complex with DCHNAQ and zephiramine. The solid–state absorbance of the complex on the membrane filter is measured at 655 nm against a blank thin layer and the difference is calculated. The colour system obeys Beer's law from 5.0–150 ng ml^?1 of aluminium. The detection and quantification limits were calculated. The relative standard deviation for 60 ng of aluminium(III) in 20‐ml sample volume amounts 0.84% (n=10). A ligand buffer solution, composed of transcyclohexane‐1,2‐diaminetetraacetic acid with an excess of zinc(II), is effective for masking interferences from foreign ions, particularly iron(III). The proposed method was applied successfully to tap and environmental water, biological (human blood, urine, and gallstone), and soil samples.     

2‐Benzothiazolemethanol as Precursor of 2‐Aryl‐1‐(2‐benzothiazolyl)‐1‐ethanones

Abstract

2‐Benzothiazolemethanol was found to react with substituted benzaldehydes in the presence of excess chlorotrimethylsilane yielding the title ketones after aqueous work up.     

Synthesis of β-Glucosides with 3-O-Picoloyl-Protected Glycosyl Donors in the Presence of Excess Triflic Acid: A Mechanistic Study

Our previous study showed that picoloylated donors are capable of providing excellent facial stereoselectivity through the H-bond-mediated aglycone delivery (HAD) pathway. Presented herein is a detailed mechanistic study of stereoselective glycosylation with 3-O-picoloylated glucosyl donors. While reactions of glycosyl donors equipped with the 3-O-benzoyl group are typically non-stereoselective because these reactions proceed via the oxacarbenium intermediate, 3-O-picoloylated donors are capable of providing enhanced, but somewhat relaxed, β-stereoselectivity by the HAD pathway. In an attempt to refine this reaction, we noticed that glycosylations are highly β-stereoselective in the presence of NIS and stoichiometric TfOH. The HAD pathway is highly unlikely because the picoloyl nitrogen is protonated under these reaction conditions. The protonation and glycosylation were studied by low-temperature NMR, and the intermediacy of the glycosyl triflate has been observed. This article is dedicated to broadening the scope of this reaction in application to a variety of substrates and targets.     

Modified One‐Pot Protocol for the Preparation of Thioglycosides from Unprotected Aldoses via S‐Glycosyl Isothiouronium Salts*

An efficient one‐pot protocol for the direct preparation of thioglycosides starting from unprotected reducing sugars via S‐glycosyl isothiouronium salts is reported. In this one‐pot methodology, BF₃ · OEt₂ has been used as a general catalyst for both per‐O‐acetylation of sugars and conversion of sugar per‐O‐acetates into S‐glycosyl isothiouronium salts, which was allowed to react with alkylating agents in the presence of a base to furnish thioglycosides in excellent yield.     

Oxidative Conversion of 3‐Alkoxyfurans to 2‐Hydroxy‐3(2H)‐furanones and 2‐Hydroxy‐2‐butene‐1,4‐diones with 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) or Phenyltrimethylammonium Tribromide (PTAB) in t‐BuOH

2‐Alkoxy‐1,3,4‐triphenylfurans were oxidized to 3‐alkoxy‐2,4,5‐triphenyl‐ 2‐butene‐1,4‐diones with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) in t‐BuOH. In contrast, various 3‐alkoxy‐2,4,5‐triphenylfurans were directly converted to 2‐hydroxy‐3(2H)‐furanone with phenyltrimethylammonium tribromide (PTAB) in t‐BuOH. The oxidative ring opening of 3‐alkoxy‐2,5‐diphenylfurans to cis‐2‐hydroxy‐2‐butene‐1,4‐dione was also accomplished with PTAB in t‐BuOH under the same reaction conditions.     

Application of Ball Milling Technology to Carbohydrate Reactions‐II. Solvent‐Free Mechanochemical Synthesis of Glycosyl Azides‡

Glycosyl azides have been prepared from a range of readily available glycosyl halides by a solvent‐free mechanochemical procedure employing a planetary ball mill in good to excellent yields.