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Deoxy sugars represent an important class of carbohydrates, present in a large number of biomolecules involved in multiple biological processes. In various antibiotics, antimicrobials, and therapeutic agents the presence of deoxygenated units has been recognized as responsible for biological roles, such as adhesion or great affinity to receptors, or improved efficacy. The characterization of glycosidases and glycosyltranferases requires substrates, inhibitors and analogous compounds. Deoxygenated sugars are useful for carrying out specific studies for these enzymes. Deoxy sugars, analogs of natural substrates, may behave as substrates or inhibitors, or may not interact with the enzyme. They are also important for glycodiversification studies of bioactive natural products and glycobiological processes, which could contribute to discovering new therapeutic agents with greater efficacy by modification or replacement of sugar units. Deoxygenation of carbohydrates is, thus, of great interest and numerous efforts have been dedicated to the development of methods for the reduction of sugar hydroxyl groups. Given that carbohydrates are the most important renewable chemicals and are more oxidized than fossil raw materials, it is also important to have methods to selectively remove oxygen from certain atoms of these renewable raw materials. The different methods for removal of OH groups of carbohydrates and representative or recent applications of them are presented in this chapter. Glycosidic bonds in general, and 2-deoxy glycosidic linkages, are included. It is not the scope of this survey to cover all reports for each specific technique.

An automated continuous flow system capable of producing protected deoxy-sugar donors from commercial material is described. Four 2,6-dideoxy and two 3-amino-2,3,6-trideoxy sugars with orthogonal protecting groups were synthesized in 11-32 % overall yields in 74-131.5 minutes of total reaction time. Several of the reactions were able to be concatenated into a continuous process, avoiding the need for chromatographic purification of intermediates. The modular nature of the experimental setup allowed for reaction streams to be split into different lines for the parallel synthesis of multiple donors. Further, the continuous flow processes were fully automated and described through the design of an open-source Python-controlled automation platform., (© 2021 Wiley-VCH GmbH.)

An efficient three component coupling of aromatic aldehyde, deoxy sugar based alkyne (α-2-deoxy propargyl glycoside) and heterocyclic amine have been refluxed to synthesize stereoselective chiral propargylamines with good to excellent yield using only CuI catalyst along with bifunctional ligand l-proline. This method has proved to be applicable in wide range of substrates and found highly enantioselective with respect to earlier reported methods. In addition, l-proline was found as a chiral source which demonstrated that it could be developed as a highly enantioselective method for the construction of deoxy sugar based chiral propargylamines. The ligand l-proline was used for the first time in enantioselective A 3 -coupling reaction of α-2-deoxy propargyl glycosides involving substituted aromatic aldehyde and heterocyclic amines. Herein, we have synthesized 15 novel compounds based on A 3 -coupling reaction and structures of all the enantioselective compounds were characterised by TLC and NMR spectroscopy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An efficient divergent synthetic strategy that leverages the natural product spectinomycin to access uniquely functionalized monosaccharides is described. Stereoselective 2'- and 3'-reduction of key spectinomycin-derived intermediates enabled facile access to all eight possible 2,3-stereoisomers of 4,6-dideoxyhexoses as well as representative 3,4,6-trideoxysugars and 3,4,6-trideoxy-3-aminohexoses. In addition, the method was applied to the synthesis of two functionalized sugars commonly associated with macrolide antibiotics-the 3- O -alkyl-4,6-dideoxysugar d-chalcose and the 3- N -alkyl-3,4,6-trideoxysugar d-desosamine.

Rhamnan and rhamnan sulfate are naturally occurring carbohydrates that have important biological functions and possible therapeutic applications, but studies are limited to the microheterogeneous mixtures from natural sources. This work reports the first synthesis of any sulfated rhamnan fragments and successful automation of the process with a recently developed automated solution-phase approach using N-iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf) promotor and levulinoyl ester deprotection conditions. The automated solution-phase activation/deprotection approach was initially able to create alpha 1 → 2, 1 → 3 type rhamnan di- and trisaccharide in moderate yields. Once these targets were achieved, a process to use SO 3 •pyridine complex in DMF for sulfation compatible with an automated solution-phase liquid handling system was developed and successfully applied to carbohydrate sulfation to create two rhamnan sulfate fragments with differing monosulfation patterns., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Control of glycoside bond stereochemistry is the central challenge in the synthesis of oligosaccharides. 2-Deoxyglycosides, which lack a C2 substituent to guide stereoselectivity, are among the most difficult classes of glycoside bond constructions. Here we present a method to synthesize 2-deoxysaccharides with specified glycoside bond stereochemistry using a nucleophilic carbohydrate residue and the synthetic equivalent of an alcohol electrophile. Because the configuration of the nucleophile can be precisely controlled, both α- and β-glycosides can be synthesized from the same starting material in nearly all cases examined. Stereoselectivities in these reactions are often greater than 50:1 and yields typically exceed 70%. This strategy is amenable to the stereocontrolled syntheses of trisaccharide diastereomers, and a tetrasaccharide. This method may be extensible to other classes of carbohydrates.

One critical part of the synthesis of heparinoid anticoagulants is the creation of the L-iduronic acid building block featured with unique conformational plasticity which is crucial for the anticoagulant activity. Herein, we studied whether a much more easily synthesizable sugar, the 6-deoxy-L-talose, built in a heparinoid oligosaccharide, could show a similar conformational plasticity, thereby can be a potential substituent of the L-idose. Three pentasaccharides related to the synthetic anticoagulant pentasaccharide idraparinux were prepared, in which the L-iduronate was replaced by a 6-deoxy-L-talopyranoside unit. The talo-configured building block was formed by C4 epimerisation of the commercially available L-rhamnose with high efficacy at both the monosaccharide and the disaccharide level. The detailed conformational analysis of these new derivatives, differing only in their methylation pattern, was performed and the conformationally relevant NMR parameters, such as proton-proton coupling constants and interproton distances were compared to the corresponding ones measured in idraparinux. The lack of anticoagulant activity of these novel heparin analogues could be explained by the biologically not favorable 1 C 4 chair conformation of their 6-deoxy-L-talopyranoside residues.

Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

A next-generation reagent-controlled approach for the synthesis of 2,6-dideoxy and 2,3,6-trideoxy sugar donors in good yield and high β-selectivity is reported. The use of p-toluenesulfonyl chloride and potassium hexamethyldisilazide (KHMDS) greatly simplifies deoxy-sugar glycoside construction, and can be used for gram-scale glycosylation reactions. The development of this approach and its application to the construction of β-linked deoxy-sugar oligosaccharides are described., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Routes for efficient synthesis of four (4"-, 2"-, 2'-, and 6-) monodeoxy analogs of the trisaccharide α-D-Glcp-(1 → 3)-α-D-Manp-(1 → 2)-α-D-ManpOMe have been developed. For the introduction of the 2'- and 2"-deoxy motifs the most efficient way was to use a 1,2-di-bromo-mannosyl donor in silver triflate-promoted couplings to construct the α-glycosidic linkage followed by reduction of the 2-bromo-function to a 2-deoxy motif at the di- or trisaccharide level. In contrast, the 4"- and 6-deoxy functions were introduced already at the monosaccharide stage. The most challenging part of the syntheses was the stereoselective formation of the non-reducing end cis-α-D-glucosidic linkages. The established α-directing effect of a 3-O-acetyl group in glucosyl donors was explored but the magnitude of the effect was variable and dependent on donor/acceptor structure and nature of promoter and an optimization had to be made for each individual glycosylation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

2-Deoxy sugars and their derivatives occur abundantly in many pharmaceutically important natural products. However, the construction of specific 2-deoxy-glycosidic bonds remains as a challenge. Herein, we report an efficient way to prepare 2-deoxy-α-glycosides by glycosylation of 2-iodo-glycosyl acetate and subsequent visible-light-mediated tin-free reductive deiodination. We have successfully applied the postglycosylational-deiodination strategy in the synthesis of more than 30 mono-, di-, tri-, tetra- and pentadeoxysaccharides with excellent stereoselectivity and efficiency. This method has also been applied to the synthesis of a 2-deoxy-tetrasaccharide containing four α-linkages., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A concise gram-scale synthesis of protected colitose thioglycosides for use in bacterial carbohydrate antigen synthesis is described. The synthesis proceeds in six steps and 59-70% overall yield from commercially available l-fucose, making it the most efficient route reported to date. Key steps include regioselective installation of a thiocarbonate using catalytic dioctyltin dichloride (10 mol%) and a tris(trimethylsilyl)silane-mediated radical deoxygenation.

Burkholderia pseudomallei and Burkholderia mallei are potential bioterrorism agents. They express the same capsular polysaccharide (CPS), a homopolymer featuring an unusual [→3)-2-O-acetyl-6-deoxy-β-D-manno-heptopyranosyl-(1→] as the repeating unit. This CPS is known to be one of the main targets of the adaptive immune response in humans and therefore represents a crucial subunit candidate for vaccine development. Herein, the stereoselective synthesis of mono- and disaccharidic fragments of the B. pseudomallei and B. mallei CPS repeating unit is reported. The synthesis of 6-deoxy-β-D-manno-heptosides was investigated using both inter- and intramolecular glycosylation strategies from thio-manno-heptose that was modified with 2-naphthylmethyl (NAP) at C2. We show here that NAP-mediated intramolecular aglycon delivery (IAD) represents a suitable approach for the stereocontrolled synthesis of 6-deoxy-β-D-manno-heptosides without the need for rigid 4,6-O-cyclic protection of the sugar skeleton. The IAD strategy is highly modular, as it can be applied to structurally diverse acceptors with complete control of stereoselectivity. Problematic hydrogenation of the acetylated disaccharides was overcome by using a microfluidic continuous flow reactor.

2-Deoxy-2-fluoroglycosides bearing dibenzyl phosphate and phosphonate aglycones were synthesised and tested as covalent inactivators of several retaining α- and β-glycosidases. β-d-Gluco-, -manno- and -galacto-configured benzyl-benzylphosphonate derivatives efficiently inactivated β-gluco-, β-manno- and β-galactosidases, while α-gluco- and α-manno-configured phosphate and phosphonate derivatives served instead as slow substrates.

2-Deoxyglycosides were synthesized in high α-selectivity by the direct addition of alcohols to D-glucal and D-galactal catalyzed by TMSI and PPh(3). The acid labile isopropylidene group is tolerated under this condition., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A low molecular weight fraction, designated LMWP, was prepared by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum and purified by anion-exchange and gel-permeation chromatography. Chemical and spectroscopic analyses showed that LMWP was mainly composed of rhamnose, and its molecular weight was about 33.6 kDa. The backbone of LMWP consists of 1,3-linked α-L-rhamnose units with partially sulfate groups at the C-2 position. Approximately 25% of 1,3-linked α-L-rhamnose units is substituted at C-2 by sulfated or non-sulfated 1,3-linked α-L-rhamnose and 1,2-linked α-L-rhamnose units. LMWP effectively prolonged clotting time as evaluated by the activated partial thromboplastin time assay and was a potent thrombin inhibitor mediated by heparin cofactor II. The investigation demonstrated that LMWP is a novel sulfated polysaccharide with anticoagulant activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A divergent, practical, and efficient de novo synthesis of fully functionalized L-colitose (3,6-dideoxy-L-galactose), 2-epi-colitose (3,6-dideoxy-L-talose), and L-rhodinose (2,3,6-trideoxy-L-galactose) building blocks has been achieved using inexpensive, commercially available (S)-ethyl lactate as the starting material. The routes center around a diastereoselective Cram-chelated allylation that provides a common homoallylic alcohol intermediate. Oxidation of this common intermediate finally resulted in the synthesis of the three monosaccharide building blocks.

The addition of 4 eq of chloral to osmundalactone (4S,5R)-4 gave quantitative formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane sulfonic acid to afford the intramolecular Micheal addition product (+)-(3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-δ-lactone in 78% overall yield from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D-digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl-osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic catalyst gave 3,4-trans-δ-lactone (-)-(3S,4R,5S)-20 in 28% yield and 3,4-cis-δ-lactone (-)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (-)-(3S,4R,5S)-20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall yield, while Dibal-H reduction of (-)-(3R,4R,5S)-21 followed by catalytic hydrogenation provided L-cymarose (7) in 85% overall yield.

A highly divergent synthesis of α-fuco-, α-6-deoxy-allo-, α-6-deoxy-altro-pyranosides has been achieved. This route utilizes a Wharton rearrangement as part of a new post-glycosylation transformation strategy., (This journal is © The Royal Society of Chemistry 2011)

Introduction: Several clinical studies have shown low or no expression of GLUT1 in breast cancer patients, which may account for the low clinical specificity and sensitivity of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) used in positron emission tomography (PET). Therefore, it has been proposed that other tumor characteristics such as the high expression of GLUT2 and GLUT5 in many breast tumors could be used to develop alternative strategies to detect breast cancer. Here we have studied the in vitro and in vivo radiopharmacological profile of 6-deoxy-6-[(18)F]fluoro-D-fructose (6-[(18)F]FDF) as a potential PET radiotracer to image GLUT5 expression in breast cancers., Methods: Uptake of 6-[(18)F]FDF was studied in murine EMT-6 and human MCF-7 breast cancer cells over 60 min and compared to [(18)F]FDG. Biodistribution of 6-[(18)F]FDF was determined in BALB/c mice. Tumor uptake was studied with dynamic small animal PET in EMT-6 tumor-bearing BALB/c mice and human xenograft MCF-7 tumor-bearing NIH-III mice in comparison to [(18)F]FDG. 6-[(18)F]FDF metabolism was investigated in mouse blood and urine., Results: 6-[(18)F]FDF is taken up by EMT-6 and MCF-7 breast tumor cells independent of extracellular glucose levels but dependent on the extracellular concentration of fructose. After 60 min, 30±4% (n=9) and 12±1% (n=7) ID/mg protein 6-[(18)F]FDF was found in EMT-6 and MCF-7 cells, respectively. 6-deoxy-6-fluoro-d-fructose had a 10-fold higher potency than fructose to inhibit 6-[(18)F]FDF uptake into EMT-6 cells. Biodistribution in normal mice revealed radioactivity uptake in bone and brain. Radioactivity was accumulated in EMT-6 tumors reaching 3.65±0.30% ID/g (n=3) at 5 min post injection and decreasing to 1.75±0.03% ID/g (n=3) at 120 min post injection. Dynamic small animal PET showed significantly lower radioactivity uptake after 15 min post injection in MCF-7 tumors [standard uptake value (SUV)=0.76±0.05; n=3] compared to EMT-6 tumors (SUV=1.23±0.09; n=3). Interestingly, [(18)F]FDG uptake was significantly different in MCF-7 tumors (SUV(15 min) 0.74±0.12 to SUV(120 min) 0.80±0.15; n=3) versus EMT-6 tumors (SUV(15 min) 1.01±0.33 to SUV(120 min) 1.80±0.25; n=3). 6-[(18)F]FDF was shown to be a substrate for recombinant human ketohexokinase, and it was metabolized rapidly in vivo., Conclusion: Based on the GLUT5 specific transport and phosphorylation by ketohexokinase, 6-[(18)F]FDF may represent a novel radiotracer for PET imaging of GLUT5 and ketohexokinase-expressing tumors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An efficient and convenient method for the synthesis of 2-deoxy-2-iodo-O-glycosides from tri-O-acetyl-D-glucal with various alcohols by using I₂-Cu(OAc)₂ is described. The 21 examples of corresponding glycosides were obtained in high yields, with good anomeric selectivity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The reaction of 2,3-anti-2-tert-butyldimethylsiloxy-3-substituted butanal derivative [anti-B, (±)-10 and (±)-16] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophiles [α-furyl anion, acetate anion, and indium (In)-assisted allyl anion] has been investigated to give selectively the anti-, anti-adduct D. This anti-stereoselection could be explained by the Felkin-Anh transition state model. Thus obtained anti-, anti-adducts (±)-17 and (±)-38 were formally converted to natural products, (±)-asperlin (2) and (±)-olivose (4), respectively. The major anti-, anti-adduct (±)-26 was converted to (±)-digitoxose (3), while the minor anti-, syn-adduct (±)-27 was also converted to (±)-olivose (4). The reaction of (±)-10 with tert-butyl acetate anion gave predominantly afforded the anti-, anti-adduct (±)-23, which was converted to (±)-1,5-dideoxyhexitol (25). Alternately, the reaction of 2,3-syn-2-tert-butyldimethylsiloxy-3-p-methoxyphenoxy butanal derivative [syn-B, (±)-14] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophile (In-assisted allyl anion) afforded a ca. 1 : 1 mixture of the syn-, anti-adduct E [(±)-32 or (±)-34] and syn-, syn-adduct F [(±)-33 or (±)-35]. After separation of this mixture, (±)-34 and (±)-35 were separately converted to (±)-oliose (5) and (±)-boivinose (6), respectively.

This tutorial review covers recent research from our laboratory towards the synthesis of amino sugars and related carbohydrate mimetics employing 1,2-oxazines as crucial intermediates. The synthesis of new dideoxyamino carbohydrate derivatives, C2-branched 4-amino sugars and their mimetics, as well as sialic acid analogues, has been developed during the last few years. The results demonstrate that alkoxyallenes are ideal and versatile components for the chain elongation of carbohydrate derivatives. Our routes starting from 3,6-dihydro-2H-1,2-oxazines are presented in conjunction with two related examples from the recent literature. Finally, we discuss possible future applications of the described compounds as anti-inflammatory agents.

Reactions of amines and carbon nucleophiles with 4-sulfonyl-hex-3-enopyranoside generate a range of C-3 amino- and C-3 branched-chain sugars, which are analogues of 3-amino-3,6-dideoxy sugars and 3-C-branched-chain-3,6-dideoxy sugars. The diastereoselectivity of addition reaction is nucleophile dependent; while both nitrogen and carbon nucleophiles added in cis-fashion, amines generated C3-C4 trans-diaxial products (gulo-derivatives), and carbon nucleophiles afforded C3-C4 trans-diequatorial products (gluco-analogues).

Glycosides of 2-deoxy-sugars, monosaccharides in which the hydroxyl group at C-2 is replaced with a hydrogen atom, occur widely in natural products and therefore have been the subject of intense synthetic activity. The report summarizes recent advances in this area, with a particular focus on work published since an earlier review on the topic, in 2000 (Marzabadi, C. H.; Franck, R. W. Tetrahedron2000, 56, 8385-8417).

A route to fluvirucinins B(2-5) (the common aglycon of fluvirucins B(2)-B(5), Sch 38518, and Sch 39185) is reported for the first time. A ring-closing metathesis (RCM) generated the C6-C7 double bond, which by catalytic hydrogenation (in toluene) gave the desired epimer with a 9:1 diastereoselection. Azide 8a and carboxylic acid 5 came from ethyl-branched fragments C9-C13 (CHO at C9) and C1-C5 via an asymmetric allylation of the former and a cross metathesis (CM) followed by a ketone methylenation (with 20 mol % of DMF as a sacrificial additive) of the latter.

FDG-based imaging with positron emission tomography (PET) has been widely used in the detection of cancer, but has not reached its full potential. In breast cancer, the glucose/fructose transporter GLUT2 and the fructose transporter GLUT5 are known to be overexpressed in transformed tissues, implicating that a fructose-based analogue would be a useful target for the improved imaging of breast cancer. We have successfully synthesized the fluorinated fructose compound, 6-deoxy-6-fluoro-D-fructose (6FDF) and examined its potential for transport and accumulation in breast cancer cells. Expression analysis of GLUT isoforms was performed on two GLUT5 expressing breast cancer cell lines using western blotting and immunocytochemistry. Uptake and inhibition studies were undertaken using [14C]-labelled hexoses. Transport inhibition studies showed dose dependent inhibition of fructose transport in both cell lines by the newly synthesized 6-deoxy-6-fluoro-D-fructose (6FDF). Also, near linear uptake over time of [14C]-labelled 6FDF was observed in both cell lines. It appears that 6FDF may have great promise for use in in vivo PET imaging of breast cancer. Ongoing work will confirm the efficacy of this compound in imaging in mouse models.

Efficient synthesis of the deoxysugar part of versipelostatin (VST) was achieved by direct and stereoselective glycosylation of the reduced VST aglycon. Activation of 2-deoxyglycosyl imidate with IBr under basic conditions enables alpha-selective glycosylation of beta-2-deoxylglycosides without anomerization. Comparison of the synthetic and natural VST products using NMR indicates that versipelostatin has a beta-D-digitoxose-(1,4)-alpha-L-oleandrose-(1,4)-beta-D-digitoxose trisaccharide. In addition, results of a biological assay indicate that the deoxyoligosaccharide unit of the synthetic glycoside was important for biological activity of the compound.

The cycloaddition reaction of acylketenes with vinyl ethers affords an extremely direct route to 2,6-dideoxysugars and their methyl ethers. The lithium enolate of commercial 2,6,6-trimethyldioxinone 3 was fluorinated in good yield to afford fluorinated dioxinone 8. An illustrative range of fluorinated 2,6-dideoxysugar derivatives was prepared via the acetyl ketene-vinyl ether cycloadduct. Electronic structure calculations were carried out to investigate the effect of the fluorine atom on ease of formation and subsequent reaction of the (fluoroacetyl)ketene reactive intermediate. A single fluorine atom lowers the barrier to fragmentation by ca. 7.5 kJ mol(-1), consistent with experimental findings, but has almost no effect on the barrier to rate determining vinyl ether addition, or to oxoketene dimerisation.

Many biologically active bacterial natural products contain highly modified deoxysugar residues that are often critical for the activity of the parent compounds. Most of these deoxysugars are secondary metabolites that are biosynthesized in the form of nucleotide diphosphate (NDP) sugars prior to their transfer to natural product aglycones by glycosyltransferases. Over the past decade, many biosynthetic pathways that lead to the formation of these unusual sugars have been unraveled, and the mechanisms of many key enzymatic transformations involved in these pathways have been elucidated. However, obtaining workable quantities of NDP-deoxysugars for in vitro studies is often a difficult task. This limitation has hindered an in-depth investigation of the substrate specificity of deoxysugar biosynthetic enzymes, many of which are promiscuous with respect to their NDP-sugar substrates and are, thus, potentially useful catalysts for natural product glycoengineering. Presented in this review are procedures for the enzymatic synthesis and purification of a variety of NDP-deoxysugars, including some early intermediates in NDP-deoxysugar biosynthetic pathways, and highly modified NDP-deoxysugars that are late intermediates in their respective biosynthetic pathways. The procedures described herein could be used as general guidelines for the development of specific protocols for the synthesis of other NDP-deoxysugars.

When 3-C-sulfonyl-pent-2-enofuranosides and 3-C-sulfonyl-hex-2-enofuranosides were reacted with primary and secondary amines, only the beta-anomeric methoxy group of the pent-2-enofuranoside did not cause any hindrance to incoming nitrogen nucleophiles. This resulted in the 'unusual' addition of amines, in which the diastereoselectivity of the reaction was overwhelmingly in favor of amino sugars of the D-arabino configuration. Selected products were desulfonylated to obtain a new class of beta-anomeric 2-amino-2,3-dideoxy-D-threo-pentofuranosides.

Synthesis of 2-deoxy-D-arabino/lyxo-hexopyranosyl disaccharides is reported. In these, the disaccharides contain 2-deoxy-arabino-hexopyranosyl and 2-deoxy-lyxo-hexopyranosyl sugars as either the reducing or the non-reducing or both the sugar units of the disaccharides. The activated 2-deoxy-1-thioglycosides served as the common precursors to prepare the 2-deoxy disaccharides with the above configurations.

Over-expressed GerB (dTDP-4-keto-6-deoxy-d-glucose aminotransferase) of Streptomyces sp. GERI-155 was used in the enzymatic synthesis of dTDP-4-amino-4,6-dideoxy-D-glucose (2) from dTDP-4-keto-6-deoxy-D-glucose (1). [Carbohydrate structure: see text]. Five enzymes including dTMP kinase (TMK), acetate kinase (ACK), dTDP-glucose synthase (TGS), dTDP-glucose 4,6-dehydratase (DH), and dTDP-4-keto-6-deoxy-d-glucose aminotransferase (GerB) were used to synthesize 2 on a large scale from glucose-1-phosphate and TMP. A conversion yield of up to 57% was obtained by HPLC peak integration given a reaction time of 270min. After purification by two successive preparative HPLC systems, the final product was identified by HPLC and then analyzed by (1)H, (13)C, (1)H-(1)H COSY NMR spectrometry.

The synthesis of either anomers of aryl 2-deoxy-D-glycopyranosides from 2-deoxy-1-thioglycosides is reported. The alpha-anomers form as the major product when thioglycosides react with differently substituted phenols and naphthols, in the presence of N-iodosuccinimide/triflic acid. On the other hand, reaction of the thioglycosides with bromine initially, followed by reaction with aryloxy anions lead to aryl 2-deoxy-beta-D-glycosides with high specificities.

A chemoenzymatic synthesis of deoxy sugar esters is described. The synthesis is based on the O-alkylation of carboxylic acid with 2-bromo-5-acetoxypentanal. The method allows treatment of hydroxy carboxylic acids without protection of alcoholic hydroxyl groups. Several stereoisomeric deoxy sugar esters were resolved (up to ee or de > 98%) using a lipase-catalyzed acetylation of hemiacetals that in certain cases afforded deoxy sugar derivatives in the form of aldehydes. The stereochemistry of the reactions was determined by the NMR spectra of mandelic acid derivatives.

A photoinduced electron-transfer (PET) reaction was used for the deoxygenation at C-2 of aldonolactones derivatized as 2-O-[3-(trifluoromethyl)benzoyl] or benzoyl esters. By irradiation of different D-galactono- and D-glucono-1,4-derivatives, with a 450W lamp, using 9-methylcarbazole as photosensitizer, the corresponding 2-deoxy-D-lyxo- and 2-deoxy-D-arabino-hexono-1,4-lactones were efficiently obtained.

Six (3,4,4',6',3'' or 6'')-monodeoxy analogues of the title trisaccharide (1-6) have been prepared utilising monodeoxy monosaccharide precursors. The reducing end deoxy derivatives were synthesised by N-iodosuccinimide/silver trifluoromethanesulfonate (NIS/AgOTf)-promoted couplings of a common disaccharide thioglycoside donor 10 to suitably protected monodeoxy acceptors 9 and 12, affording trisaccharides, which after deprotection yielded target structures 1 and 2. The non-reducing end deoxy derivatives could similarly be produced by halide-assisted glycosylations of a common disaccharide acceptor 17 with monodeoxy glycosyl bromide donors (obtained from thioglycosides 18 and 20) to yield, after removal of protecting groups, target trisaccharides 3 and 4. The analogues with the deoxy function in the middle mannose residue, were obtained through orthogonal halide-assisted coupling of tetrabenzyl-glucopyranosyl bromide to monodeoxy thioglycoside acceptors to give thioglycoside disaccharides, which subsequently were used as donors in NIS/AgOTf-promoted couplings to a common 2-hydroxy-mannose acceptor 15 to afford trisaccharides; deprotection yielded the final target compounds 5 and 6.

The synthesis of d- and l-glycero-alpha-manno-thioheptopyranosides, protected with 4,6-O-alkylidene-type acetals is described. In glycosylations carried out with preactivation with the 1-benzenesulfinylpiperidine/trifluoromethanesulfonic anhydride couple, both the D- and L-glycero series exhibit excellent beta-selectivity with a range of glycosyl acceptors. In contrast, a 4,7-O-alkylidene acetal was found not to afford beta-selectivity. With a 4,6-O-[1-cyano-2-(2-iodophenyl)ethylidene] acetal protected thioglycoside, excellent beta-selectivity was obtained in glycosylation reactions, and subsequent treatment with tributyltin hydride and azoisobutyronitrile brought about clean fragmentation to the 6-deoxy-glycero-beta-D-manno-heptopyranosides. This chemistry was applied to the stereocontrolled synthesis of methyl alpha-L-rhamno-pyranosyl-(1-->3)-D-glycero-beta-D-manno-heptopyranosyl-(1-->3)-6-deoxy-glycero-beta-D-manno-heptopyranosyl-(1-->4)-alpha-L-rhamno-pyranoside, a component of the lipopolysaccharide from Plesimonas shigelloides.

Replacement of specific hydroxyl groups by fluorine in carbohydrates is an ongoing challenge from chemical, biological, and pharmaceutical points of view. A rapid and efficient two-step, regio- and stereoselective synthesis of 2-deoxy-2-(R)-fluoro-beta-d-allose (2-(R)-fluoro-2-deoxy-beta-d-allose; 2-FDbetaA), a fluorinated analogue of the rare sugar, d-allose, is described. TAG (3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol or 3,4,6-tri-O-acetyl-d-glucal), was fluorinated in anhydrous HF with dilute F(2) in a Ne/He mixture or with CH(3)COOF at -60 degrees C. The fluorinated intermediate was hydrolyzed in 1N HCl and the hydrolysis product was purified by liquid chromatography and characterized by 1D (1)H, (13)C, and (19)F NMR spectroscopy as well as 2D NMR spectroscopy and mass spectrometry. In addition, (18)F-labeled 2-deoxy-2-(R)-fluoro-beta-d-allose (2-[(18)F]FDbetaA) was synthesized for the first time, with an overall decay-corrected radiochemical yield of 33+/-3% with respect to [(18)F]F(2), the highest radiochemical yield achieved to date for electrophilic fluorination of TAG. The rapid and high radiochemical yield synthesis of 2-[(18)F]FDbetaA has potential as a probe for the bioactivity of d-allose.

Sunlight-mediated photooxygenation of 3-O-acetyl and 3-O-methyl derivatives of 1,2-O-alkylidene-5(E)-eno-5,6,8-trideoxy-alpha-D-xylo-oct-1,4-furano-7-uloses (1a-e) in carbon tetrachloride solution gave stable 4,7-epidioxy derivatives in 4R (2a-e) and 4S (3a-e) configurations. The presence of an endo alkyl, on the 1,2-O-alkylidene group and its size, resulted in an increase of the yield of the 4S isomers. 3-O-acetyl derivatives yielded products as a mixture of C-7 anomers, whereas 3-O-methyl derivatives gave pure single stereoisomers.

[reaction: see text] A general procedure for the stereoselective synthesis of 2-deoxy-2-iodo-hexo- and -hepto-pyranosyl glycosides from furanoses is reported. The proposed methodology provides a new route for accessing 2-deoxy-oligosaccharides. The procedure involves three reactions: Wittig-Horner olefination to give alkenyl sulfanyl derivatives, electrophilic iodine-induced cyclization to give phenyl 2-deoxy-2-iodo-1-thio-hexo-glycosides, and glycosylation. Protected furanoses 1, 3, and 6-11, which include examples of the four possible isomeric configurations of furanoses, were reacted with diphenyl phenylsulfanylmethyl phosphine oxide to give the alkenyl sulfanyl derivatives 2, 4, and 12-16. The iodine-induced cyclization of these compounds afforded the phenyl 2-deoxy-2-iodo-1-thio-glycosides 18, 20, and 22-27 with practically complete regio- and stereoselectivity. Products of 6-endo cyclization, in which the iodine at C-2 was in a cis relationship with the alkoxy at C-3, were almost exclusively produced. Better yields were obtained for compounds with a ribo or xylo configuration than for compounds with other configurations. Compounds 18, 20, and 22-27 were found to be efficient glycosyl donors in the glycosylation of cholesterol and glucopyranoside 29a, affording the corresponding 2-deoxy-2-iodo-glycosides and 2-deoxy-2-iodo-oligosaccharides with good yields and stereoselectivities. The glycosydic bond in the major isomers was always trans to the iodine at C-2.

Hexopyranoside methyl alpha-D-mannoside (8) was homologated to yield 7-(acylamino)-2,6,7-trideoxy-heptopyranosides 19-26. A crucial reaction step is the radical cleavage of benzylidene derivative 10 to obtain bromide 11. Since nucleophilic substitution of 11 with KCN provided the bicyclic nitrile 13 instead of nitrile 14, ketone 11 was protected as the dimethyl acetal 15. Nucleophilic substitution of 15 with KCN, subsequent hydrogenation with H2/Raney Ni and acylation with various carboxylic acid derivatives yielded 7-(acylamino)heptopyranosides 19-22.

Both cis- and trans-2-substituted-1,2,3,6-tetrahydro-pyridin-3-ols have been prepared via an aldol condensation-ring-closing metathesis sequence. A stereodivergent synthesis of optionally functionalized deoxyimino sugars was achieved via asymmetric dihydroxylation or epoxidation/nucleophilic substitution of these tetrahydropyridines.

In the synthesis of vinyl sulfone-modified hex-5-enofuranosides, the E/Z ratios of the products are influenced by the stereoelectronic property of a group present at the C-3 position. This observation has been utilized to influence the diastereoselectivity of addition of amines to C-5 of vinyl sulfone- modified hex-5-enofuranosides, which are efficient Michael acceptors. The stereoelectronic effect of OMe attached to the beta-face of C-3 (gluco derivative) is sufficient to impose diastereoselectivity overwhelmingly in favor of l-ido-aminosugars when the Michael acceptor is reacted with both primary and secondary amines. 3-O-Benzylated gluco derivative is also effective in producing l-ido-aminosugars but only in reactions with primary amines. The selectivity is lost when an allo derivative with OBn at the alpha-face of C-3 is used. Selected products were desulfonated to establish this new approach as a general and versatile strategy for accessing 5-amino-5-deoxysugars.

Methyl 3-azido-2,3-dideoxy-alpha-D-xylo-, -alpha-D-lyxo-, and -beta-D-xylo-hexopyranosides were converted into 4-O-acetyl-3-azido-6-iodo-2,3,6-trideoxy analogues via 6-O-p-tolylsulfonyl compounds. The elimination of hydrogen iodide from 6-iodo glycosides yielded methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-beta-L-erythro-, -alpha-L-threo-, and -beta-L-threo-hex-5-enopyranosides. The configuration and conformation of all products are evaluated in depth on the basis of (1)H and (13)C NMR data. Factors determining conformational energy in 4-O-protected-3-azido-2,3,6,-trideoxy-hex-5-enopyranosides are discussed.

We report the synthesis of the first 2',3'-diamino substituted uridine derivative with xylo-configuration, its use as starting material for the synthesis of salen-type ligands and the first structurally characterised copper(II) complex thereof.

An efficient route to various sugar lactones has been developed. Key to the overall transformation is the sequential osmium-catalyzed dihydroxylation of 2,4-dienoates. The simplest (one-step/racemic) example of this reaction occurs when the dihydroxylation is performed with aqueous NMO in MeOH. When the first dihydroxylation is performed using the AD-mix procedure, an enantioselective variant results. When a matched AD-mix procedure is used for the second dihydroxylation, an exceedingly diastereo- and enantioselective synthesis of galacto-1,4-lactone results. [Reaction: see text]

The irreversible spread of new resistance mechanisms against existing therapeutical antibiotics has led to the development of technologies and strategies for the glycosylation engineering of novel antibiotics. Amino-, C-branched and O-methylated 6-deoxyhexoses play a favourite role in the biosynthesis of clinically important antibiotics like tylosin, erythromycin or oleandomycin and are essential for the antibiotic activity. They are transferred onto the aglycon by glycosyltransferases using dTDP-activated deoxyhexoses. The in vitro biochemical characterization of the biosynthetic enzymes and the glycosyltransferases are, however, hampered due to the poor synthetic access to dTDP-activated deoxysugars and their biosynthetic intermediates. The overcoming of the poor availability of dTDP-activated sugars was the target of several researchers to fulfil their distinct aims with these sugars which were mostly involved in the synthesis of different biological active compounds. Several completely different strategies were used in the past years to improve the availability of dTDP-activated deoxysugars, varying from complete enzymatic synthesis via syntheses using reaction technology for yield optimization to full organic synthesis or shortcuts like the decomposition of commercially available antibiotics and later chemical activation of the sugar moieties. This review gives a survey of the synthesis of dTDP-activated sugars by chemical and chemoenzymatic approaches and discusses the promiscuity of glycosyltransferases to evaluate the chances for applying them for the production of new bioactive compounds. It summarizes the most important enzymes in the field of synthesis using biosynthetic pathway enzymes and describes solutions for occurring challenges during application. Finally, this review will give a survey about the availability of dTDP-activated sugars in sufficient scale and will also point at important sugars which are still bottlenecks and difficult to synthesize and therefore should become a target for enhanced research efforts.