Aglycon Delivery Research Articles

Synthesis of Docosasaccharide Arabinan Motif of Mycobacterial Cell Wall

Mycobacterial arabinan is a common constituent of both arabinogalactan (AG) and lipoarabinomannan (LAM). In this study, synthesis of β-Araf containing common arabinan docosasaccharide motif (22 Araf monomer units) of mycobacterial cell wall was achieved. Our synthetic strategy toward arabinan involves (1) the stereoselective β-arabinofuranosylation using both 3,5-O-TIPDS-protected and NAP-protected arabinofuranosyl donors for straightforward intermolecular glycosylation and intramolecular aglycon delivery (IAD), respectively, and (2) the convergent fragment coupling with branched fragments at the linear sequence using thioglycoside donor obtained from the corresponding acetonide at the reducing terminal of each fragment through a three-step procedure. Because the acetonide at the reducing terminal of all fragments would be converted to thioglycoside as the glycosyl donor, and mainly Bn ether protections were used, our strategy will be readily applicable to the synthesis of more complex arabinan, arabinogalactan, and arabinomycolate derived from mycobacterial CWS.

ChemInform Abstract: Recent Advances in Stereoselective Glycosylation Through Intramolecular Aglycon Delivery

AbstractReview: about 100 refs.

ChemInform Abstract: Highly Optimized β-Mannosylation via p-Methoxybenzyl Assisted Intramolecular Aglycon Delivery.

ChemInform Abstract: Highly Optimized β-Mannosylation via p-Methoxybenzyl Assisted Intramolecular Aglycon Delivery.

ChemInform Abstract: Stereoselective cis Glycosylation of 2-O-Allyl Protected Glycosyl Donors by Intramolecular Aglycon Delivery (IAD).

2-O-Allyl protected glycosyl donors may be glycosylated stereoselectively via a three step sequence involving double bond isomerization, N-iodosuccinimide mediated tethering to a glycosyl acceptor and subsequent intramolecular glycosylation (intramolecular aglycon delivery, IAD).

Recent advances in stereoselective glycosylation through intramolecular aglycon delivery

Methodology toward the stereoselective 1,2-cis glycoside linkage using intramolecular aglycon delivery (IAD) has been extensively developed. In the last two decades, progress has been made using various mixed acetal linkages and a number of glycosyl donor moieties to develop novel IAD strategies, mainly based on formation of acetal linkages. This account summarizes the newest naphthylmethyl (NAP) ether-mediated IAD as well as all the types of mediations for stereospecific construction of various 1,2-cis linkages, not only for beta-mannopyranoside, but also for other linkages almost without exception, including beta-L-rhamnoside.

ChemInform Abstract: Ketone Hydrosilylation with Sugar Silanes Followed by Intramolecular Aglycone Delivery: An Orthogonal Glycosylation Strategy.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ketone Hydrosilylation with Sugar Silanes Followed by Intramolecular Aglycone Delivery: An Orthogonal Glycosylation Strategy

Gettin' a little sugar-no alcohol required: A procedure for the direct glycosylation of ketones without a hydroxy intermediate enables the site-selective glycosylation of hydroxyketones at the ketone or the alcohol functionality without the use of protecting groups on the aglycone (see scheme). Site selectivity is controlled by the catalyst structure in hydrosilylation and dehydrogenative silylation reactions with sugar silanes. Bn=benzyl.

Ketone Hydrosilylation with Sugar Silanes Followed by Intramolecular Aglycone Delivery: An Orthogonal Glycosylation Strategy

AbstractSüßer Anhang nach Wunsch: Ein Verfahren zur direkten Glycosylierung von Ketonen ohne Hydroxyintermediate ermöglicht die ortsselektive Glycosylierung von Hydroxyketonen an der Keton‐ oder der Alkoholeinheit, ohne dass Schutzgruppen am Aglycon notwendig sind (siehe Schema). Die Ortsselektivität wird in den Hydrosilylierungen und dehydrierenden Silylierungen mit Zuckersilanen durch die Katalysatorstruktur bestimmt. Bn=Benzyl.magnified image

Synthesis of prospective disaccharide ligands for Escherichia coli O157 verotoxin

The synthesis of new potential ligands for Escherichia coli 0157 verotoxin is reported, based on disaccharide fragments of the tetrasaccharide glycan portion of Gb 4 glycolipid. Intramolecular aglycone delivery was employed for the high-yielding and stereoselective production of the azidopropyl-tethered α-galactoside building block.

NAP Ether Mediated Intramolecular Aglycon Delivery: A Unified Strategy for 1,2‐cis‐Glycosylation (Eur. J. Org. Chem. 25/2008)

AbstractThe cover picture shows shows the general outline for 2‐naphthylmethyl (NAP) ether mediated intramolecular aglycon delivery (NAP‐IAD). The initial formation of the mixed acetal (MA) from the NAP ether protected glycosyl donor (D) having the manno‐ or gluco‐configuration at the C2 position and the glycosyl acceptor (A), followed by stereoselective intramolecular glycosylation, afforded the desired 1,2‐cis glycoside in high yield. Stereospecific constructions of various 1,2‐cis linkages, such as β‐mannopyrano‐, β‐arabinofurano‐ and α‐glucopyranosides, were achieved through NAP‐IAD. Details are discussed in the article by A. Ishiwata, Y. Munemura and Y. Ito on p. 4250 ff.

Stereoselective Synthesis of β-l-Rhamnopyranosides

Stereoselective construction of 1,2-cis-beta-L-rhamnopyranoside was achieved by our effective methodology using naphthylmethyl (NAP) ether-mediated intramolecular aglycon delivery (IAD). The complete stereoselective synthesis of the bacterial extracellular polysaccharide, alpha-L-Rhap-(1-->3)-beta-L-Rhap-(1-->4)Glcp from Sphaerotilus natans, was successfully accomplished, clearly demonstrating that the NAP-IAD methodology is highly versatile.

Glycosylation Methods in Oligosaccharide Synthesis. Part 1

A review dealing with the general aspects of oligosaccharide synthesis including the recent advances in protecting group strategies and anomeric control for stereoselective glycosylations, focusing on the formation of 1,2-cis-glycosides, are presented. Recent examples of the intramolecular aglycon delivery approach and of the remote effect on the stereochemistry of the new glycosidic bond are considered. In this part, updated examples of the use of glycosyl halides, thioglycosides, sulfoxides and phenylselenides as glycosylating agents for oligosaccharide synthesis are also discussed.

Synthetic Studies toward Mycobacterium tuberculosis Sulfolipid-I

Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. Here we describe the synthesis of a SL-I analogue bearing unnatural lipid substituents. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. The route developed for the model compound can be readily extended to the synthesis of native SL-I as well as additional analogues for use in the investigation of SL-I's functions.

Probing osmotic effects on invertase with L-(-)-sucrose.

L-(-)-sucrose was efficiently synthesized using intramolecular aglycon delivery and used to elucidate osmotic effects on the activity of invertase, which catalyzes the hydrolysis of D-(+)-sucrose. The osmotic effect imposed by L-sucrose was responsible for more than 30% of the activity loss ascribed otherwise to "substrate inhibition."

Propargyl mediated intramolecular aglycon delivery (IAD): applications to the synthesis of core N-glycan oligosaccharides

The use of propargyl mediated intramolecular aglycon delivery (IAD) for the synthesis of the key Manβ(1→4)GlcNAc linkage of N-glycan oligosaccharides, including the core N-glycan pentasaccharide, is investigated. Isomerisation of a 2- O-progargyl group of manno thioglycoside donors to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of protected GlcNAc acceptors, and subsequent intramolecular glycosylation occurs with complete control of anomeric stereochemistry to form the Manβ(1→4)GlcNAc linkage. A variety of linear and convergent approaches (1+2, 3+1, 3+2) to the core pentasaccharide are investigated as means of probing the generality and limitations of this type of intramolecular aglycon delivery for the formation of β-mannoside linkages in complex oligosaccharides.

β-Mannosylation of N-acetyl glucosamine by propargyl mediated intramolecular aglycon delivery (IAD): synthesis of the N-glycan core pentasaccharide

An efficient and completely stereocontrolled synthesis of the N-glycan Manβ(1–4)GlcNAc disaccharide is achieved by propargyl mediated intramolecular aglycon delivery (IAD). Isomerisation of the 2- O-progargyl group of a manno thioglycoside to an allene is followed by iodonium ion mediated mixed acetal formation with the 4-OH of a protected GlcNAc derivative, and subsequent intramolecular glycosylation with complete control of anomeric stereochemistry. Access to this key disaccharide intermediate allows completion of the total synthesis of the core N-glycan pentasaccharide.

Comprehensive synthesis of ER related high-mannose-type sugar chains by convergent strategy

Systematic synthesis of high-mannose-type sugar chains of asparagine-linked glycoproteins is described. To construct the target sugar chains, we employed the convergent route, using three oligosaccharide components, the common hexasaccharide, branched tri-, tetra- and pentasaccharides, and mono-, di-, and triglucosyl fragments. Construction of the β-mannoside linkage was performed using p-methoxybenzyl-assisted intramolecular aglycon delivery. The hexasaccharide fragment was coupled with the branched mannooligosaccharide donors such as M5, M4B, M4C, and M3 to give undecasaccharide (M9), decasaccharide (M8B and M8C), and nonasaccharide (M7), respectively. Incorporation of mono-, di-, and triglucosyl fragments toward them gave tetradecasaccharide (G3M9), tridecasaccharide (G2M9), dodecasaccharide (G1M9), undecasaccharide (G1M8B and G1M8C), and decasaccharide (G1M7), respectively.

Synthesis of the Glc 3Man N-glycan tetrasaccharide by iterative allyl IAD

The synthesis of the tetrasaccharide α- d-Glc p-(1→2)-α- d-Glc p-(1→3)-α- d-Glc p-(1→3)-α- d-Man p-OMe, corresponding to the terminal tetrasaccharide portion of the glucose terminated arm of the N-glycan tetradecasaccharide, was achieved with complete stereocontrol by the use of iterative allyl protecting group mediated intramolecular aglycon delivery (allyl IAD) demonstrating the utility of intramolecular glycosylation for the stereocontrolled construction of multiple glycosidic linkages during the synthesis of an oligosaccharide.

Allyl protecting group mediated intramolecular aglycon delivery: optimisation of mixed acetal formation and mechanistic investigation

An efficient protocol for the formation of α-iodo mixed acetals, the first step of allyl-mediated IAD, by reaction of allyl-derived enol ethers and alcohols, using I 2, AgOTf and di- tert-butyl methylpyridine as a novel source of I +, is reported. This reagent combination is capable of tethering glycosyl donors to the secondary alcohol groups of a variety of glycosyl acceptors including mono-, di- and trisaccharides. Mechanistic studies confirm the intramolecular nature of the glycosylation reaction, whilst the attempted use of diol glycosyl acceptors reveals limitations of both regio- and stereoselectivity in the glycosylation step.

Stereospecific synthesis of 1,2-cis glycosides by vinyl-mediated IAD.

[reaction: see text] Stereospecific 1,2-cis glycosylation of 2-O-vinyl thioglycosides, synthesized from the corresponding alcohols by Ir-catalyzed transvinylation with vinyl acetate, is achieved by iodine-mediated tethering of a range of primary and secondary carbohydrate acceptors, followed by intramolecular aglycon delivery (IAD). The use of such an intramolecular glycosylation strategy furnishes the desired alpha-gluco and beta-manno disaccharides in an entirely stereoselective manner.