Iterative Glycosylation Research Articles

Synthesis of N,N’-Diacetyl-β-Chitobiosyl N-Glycooxazoline

The synthesis of N,N’-diacetyl-β-chitobiosyl N-glycooxazoline 2 was investigated. A routine method was used to prepare the N-benzyloxycarbonyl (Cbz) protected trichloroacetimidate donors 11 and 13. The synthesis was carried through using polystyrene as solid-phase support and o-nitrobenzyl ether tether as linker. The target compound 2 was efficiently obtained by iterative glycosylations, catalytic hydrogenation, acetylation, deacetylation, and photolysis.

ChemInform Abstract: In situ Formation of β‐Glycosyl Imidinium Triflate from Participating Thioglycosyl Donors: Elaboration to Disarmed—Armed Iterative Glycosylation

Abstract16 examples for disaccharides, 3 examples for trisaccharides

High-Efficiency Synthesis of N,N ’ -Diacetyl-β-Chitobiosyl Allosamizoline

The high-efficiency synthesis of N,N’-diacetyl-β-chitobiosyl allosamizoline 2 was investigated. The Nbenzyloxycarbonyl (Cbz) protected trichloroacetimidate donors 11 and 13 were synthesized by routine method. The solidphase synthesis was performed using polystyrene as support and o-nitrobenzyl ether tether as linker. The target allosamidin analogue 2 was efficiently obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, deacetylation, and photolysis, respectively. Keywords: N, N’-Diacetyl-β-chitobiosyl allosamizoline, Synthesis, Trichloroacetimidate donors, o-nitrobenzyl ether, Photolysis, pseudotrisaccharide allosamidin, 5-hydroxy-2-nitrobenzaldehyde, polystyrene resin, saccharide

High-Efficiency Synthesis of N,N ’ -Diacetyl-β-Chitobiosyl Allosamizoline

The high-efficiency synthesis of N,N’-diacetyl-β-chitobiosyl allosamizoline 2 was investigated. The Nbenzyloxycarbonyl (Cbz) protected trichloroacetimidate donors 11 and 13 were synthesized by routine method. The solidphase synthesis was performed using polystyrene as support and o-nitrobenzyl ether tether as linker. The target allosamidin analogue 2 was efficiently obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, deacetylation, and photolysis, respectively.

ChemInform Abstract: Recent Progress on Synthesis and Activities of Allosamidin and Its Analogues

AbstractReview: 39 refs.

An Efficient Synthesis of Allosamidin

The solid-phase synthesis of allosamidin was investigated. After two N-benzyloxycarbonyl (Cbz)-protected trichloroacet­imidate donors were synthesized, the solid-phase synthesis was performed using polystyrene as support and an o-nitrobenzyl ether tether as linker. The target allosamidin was efficiently obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, deacetylation, and photolysis.

Synthesis of the Tetrasaccharide Motif and Its Structural Analog Corresponding to the Lipopolysaccharide of Escherichia coli O75

BackgroundExtraintestinal pathogenic E. coli are mostly responsible for a diverse spectrum of invasive human and animal infections leading to the urinary tract infections. Bacterial lipopolysaccharides are responsible for their pathogenicity and their interactions with host immune responses. In spite of several breakthroughs in the development of therapeutics to combat urinary tract infections and related diseases, the emergence of multidrug-resistant bacterial strains is a serious concern. Lipopolysaccharides are attractive targets for the development of long-term therapeutic agents to eradicate the infections. Since the natural sources cannot provide the required amount of oligosaccharides, development of chemical synthetic strategies for their synthesis is relevant to gain access to a reservoir of oligosaccharides and their close analogs.MethodologyTwo tetrasaccharide derivatives were synthesized from a single disaccharide intermediate. β-d-mannoside moiety was prepared from β-d-glucoside moiety following oxidation–reduction methodology. A [2+2] stereoselective block glycosylation strategy has been adopted for the preparation of tetrasaccharide derivative. α-d-Glucosamine moiety was prepared from α-d-mannosidic moiety following triflate formation at C-2 and SN 2 substitution. A one-pot iterative glycosylation exploiting the orthogonal property of thioglycoside was carried out during the synthesis of tetrasaccharide analog.ResultsSynthesis of the tetrasaccharide motif (1) and its structural analog (2) corresponding to the lipopolysaccharide of Escherichia coli O75 was successfully achieved in excellent yield. Most of the reactions are clean and high yielding. Both compounds 1 and 2 were synthesized as their 4-methoxyphenyl glycoside, which can act as a temporary anomeric protecting group for further use of these tetrasaccharides in the preparation of glycoconjugates.

Recent Progress on Synthesis and Activities of Allosamidin and Its Analogues

The pseudotrisaccharide allosamidin 1 is a potent family-18 chitinase inhibitor, and it demonstrates biological activities against insects and fungi. Recent development for the synthesis and activities of compound 1 and its analogues was reviewed. Huang et al. described the solid-phase synthesis of allosamidin 1 and its analogues, which were obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively. It indicated that di-N-acetyl-β-chitobiosyl allosamizoline was strongly against insect chitinase from Bombyx mori. Withers and his coworkers have synthesized chitobiose and chitotriose thiazolines, which exhibit chitinase inhibition activity.

In situ formation of β-glycosyl imidinium triflate from participating thioglycosyl donors: elaboration to disarmed–armed iterative glycosylation

β-Glycosyl imidinium triflate is generated from participating thioglycoside donors for disarmed-armed iterative glycosylations and one-pot oligosaccharide synthesis.

Chitinase Inhibitor Allosamidin and Its Analogues: An Update

The pseudotrisaccharide allosamidin 1 is a potent family-18 chitinase inhibitor, and it demonstrates biological activities against insects, fungi, and the Plasmodium falciparum life cycle. Compound 1 contains two N-acetylhexosamine residues with the unusual D-allo-configuration and a novel aminocyclitol (i.e. allosamizoline 2), joined by two β-(1→4) glycosidic bonds. Many traditional syntheses of compounds 1-2 and their analogues have been reported. Herein, recent development for the synthesis of compounds 1-2 and their analogues was reviewed. Donohoe and Rosas approach to allosamizoline 2 involves a key-step ring-closing metathesis (RCM) to form the cyclopentene core followed by halocyclization to form the oxazoline unit. Rojas et al. reported that rhodium-catalyzed oxidative cyclization of glucal 3-carbamates led to oxazolidinone-protected mannosamine derivatives. Huang et al. described the solid-phase synthesis of allosamidin 1 and its analogues. The compound 1 and its analogues were obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively. Withers and his co-workers research shows that chitobiose and chitotriose thiazolines exhibit chitinase inhibition activity. In a word, the goal is to investigate the novel methods for the synthesis of allosamidin and its analogues, which is convenient for the discovery of allosamidin analogues with high activity. Keywords: Allosamidin, allosamizoline, analogues, synthesis, recent development, Plasmodium falciparum, ring-closing metathesis (RCM), iterative glycosylation reactions, acetylation, catalytic hydrogenation, deacetylation, chitinase inhibition activity, allosamidin analogues, pseudotrisaccharide, aminocyclopentitol moiety

Solid-Phase Synthesis of Di-N-Acetyl-β-Chitobiosyl Allosamizoline

The solid-phase synthesis of di-N-acetyl-β-chitobiosyl allosamizoline 2 was reported. After the 6-O-benzyl allosamizoline 16, NHCbz trichloroacetimidate donors 7, and 14 were synthesized; solid-phase synthesis was performed using the Wang resin as support. The target di-N-acetyl-β-chitobiosyl allosamizoline 2 was obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively. Keywords: Allosamidin analogue, di-N-acetyl-β-chitobiosyl allosamizoline, glycosylation reactions, solid-phase synthesis, trichloroacetimidate donors, wang resin, antifungal agents, Acetylation, Regioselective, diisopropylcarbodiimide

Solid-Phase Synthesis of Di-N-Acetyl-β-Chitobiosyl NAG-Thiazoline

The solid-phase synthesis of di-N-acetyl-β-chitobiosyl NAG (N-acetyl D-glucosamine)-thiazoline 3 was reported. After the 6-O-benzyl NAG-thiazoline 9, NHCbz trichloroacetimidate donors 14, and 21 were synthesized, and solid-phase synthesis was performed using the Wang resin as support. The target di-N-acetyl-β-chitobiosyl NAGthiazoline 3 was obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively. Keywords: Di-N-acetyl-β-chitobiosyl NAG-thiazoline, Allosamidin analogue, Solid-phase synthesis, Trichloroacetimidate donors, Wang resin, Glycosylation reactions, chitinase, pseudodisaccharide, Streptomyces, thiazoline triacetate 6, Acetylation, TBDMS group, Wang-chlorinated resin, trichloroacetimidate, TMSOTf-promoted glycosylation

Convergent synthesis of the pentasaccharide repeating unit of the O-antigen of Shigella boydii type 14

An efficient synthesis of the pentasaccharide repeating unit of the O-antigen of Shigella boydii type 14 is reported. A one-pot, two step iterative glycosylation and [3+2] block synthetic strategy have been adopted for the construction of the pentasaccharide derivative 11, which was then transformed into target compound 1 after a series of functional group transformations. The primary hydroxyl group has been selectively oxidized to a carboxylic acid functionality without affecting the secondary hydroxyl groups. HClO 4–SiO 2 has been used as a solid acid substitute in all glycosylation and functional group transformations. The yields were excellent in all glycosylation steps.

High-Efficiency Synthesis of Chitooligosaccharides

The solid-phase synthesis of chitooligosaccharides is described. After the NHCbz trichloroacetimidate donors 6 and 14 were synthesized; solid-phase synthesis was performed using the Wang resin as support. The illustrated tetra-Nacetyl- chitotetraose 1 was obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively.

Solid-Phase Synthesis of Allosamidin

The solid-phase synthesis of allosamidin is described. After the NHCbz trichloroacetimidate donors were synthesized, solid-phase synthesis was performed using the Wang resin as support. The target allosamidin was obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively.

Probing the Aglycon Promiscuity of an Engineered Glycosyltransferase

Sugars appended to pharmaceutically important natural products influence key pharmacological properties and/or molecular mechanism of action.[1] However, studies designed to systematically understand and/or exploit the role of carbohydrates in drug discovery are often limited by the availability of practical synthetic and/or biosynthetic tools.[2] Among the contemporary options to address this limitation,[3–4] chemoenzymatic glycorandomization utilizes a set of flexible enzymes consisting of an anomeric kinase, sugar-1-phosphate nucleotidylytransferase, and natural product glycosyltransferase (GT).[4–6] While chemoenzymatic glycorandomization has been successfully applied to alter the natural sugar moieties of numerous natural products,[4–8] the process remains primarily restricted by enzyme specificity and availability of suitable GTs for the target of interest. Thus, although there is precedent for improving non-glycosylated therapeutics via glycoconjugation, including colchicine,[9] mitomycin,[10] podophyllotoxin,[11] rapamycin,[12] isophosphoramide mustards,[13] or taxol,[14] such targets remain beyond chemoenzymatic strategies. Recent studies on OleD, the oleandomycin (1) GT from Streptomyces antibioticus (Scheme 1a), revealed an enhanced triple mutant (A242V/S132F/P67T, referred to herein as ‘ASP’) that displayed marked improvement in proficiency and substrate promiscuity.[4] To probe the synthetic utility of this enhanced catalyst and expand upon previous reports of acceptor promiscuity for wild-type (WT) OleD,[15] we report a comparison of the aglycon specificities of the WT and ‘ASP’ OleD variants toward 137 drug-like acceptors. This study highlights the ability of OleD variants to glucosylate a total of 71 diverse acceptors, catalyze iterative glycosylation with numerous substrates, and establishes OleD as the first multifunctional GT capable of generating O-, S- and N-glycosides.

Synthesis of the Antigenic Tetrasaccharide Side Chain from the Major Glycoprotein of Bacillus anthracis Exosporium

A synthesis of the pentenyl glycoside of the tetrasaccharide side chain from the major glycoprotein of Bacillus anthracis by a [3 + 1] approach is described. The construction of the 1,2-trans-glycosidic linkage in the terminal anthrose moiety was achieved through the application of known alpha-nitrilium ion-mediated beta-selective glycosylation methodology. An iterative glycosylation strategy was used for the assembly of the trirhamnan building block. A new route to the anthrose saccharide was developed from D-galactose.

Glycosylation under Thermodynamic Control: Synthesis of the Di‐ and the Hexasaccharide Fragments of the O‐SP of Vibrio Cholerae O:1 Serotype Ogawa from Fully Functionalized Building Blocks

AbstractThe known 5‐(methoxycarbonyl)pentyl α‐glycoside of the hexasaccharide of the O‐SP of Vibrio cholerae O:1, serotype Ogawa 31 was newly prepared from side‐chain‐equipped disaccharide building blocks. The intermediate tetrasaccharide 25 was prepared from the disaccharide glycosyl acceptor 11 and the (1→2)‐linked disaccharide thioglycoside glycosyl donor 8, having a (non‐participating) saccharide moiety at C‐2 in the downstream end. When performed conventionally (at room or at sub 0 C temperatures), glycosylations with 11, carried out without anchimeric assistance, showed poor stereoselectivity but the formation of the 1,2‐trans‐glycosidic linkage could be markedly improved through thermodynamic control. This synthetic strategy towards 31 was more efficient than the step‐wise approach, which was based on iterative glycosylation of 11 with 5 followed by delevulinoylation. Thermodynamic control improved considerably the yields of glycosylation of tetrasaccharide glycosyl acceptor 26 with disaccharide donor 18, to give the fully protected hexasaccharide 28, and also a similar reaction of the thioglycoside 18 with methyl 5‐hydroxyhexanoate, to afford the linker‐equipped disaccharide 19. Sequential deacetylation and debenzylation of the hexasaccharide 28, and deprotection of one of its intermediates, 19, gave the target hexasaccharide 31, and the wanted disaccharide 22, respectively.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Highly Efficient Synthesis of Oligo‐N‐acetylglucosamines by Iterative Glycosylation of Di‐ and Tetrachlorophthaloyl‐protected Thioglucosamines.

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, please click on HTML or PDF.

Thioglycosides in Sequential Glycosylation Strategies

AbstractFor Abstract see ChemInform Abstract in Full Text.