Karl Dax

Synthesis of deoxyfluoro sugars from carbohydrate precursors.

Results obtained over the past decade concerning the introduction of the fluorine atom into carbohydrate molecules, either by nucleophilic substitution or electrophilic addition reactions, are summarised. The first section mainly deals with the triflate/fluoride tandem sequence and the DAST-reaction. In the discussion, emphasis is given to the dependency of the reaction course on the stereochemical and protecting group features. Possible reaction pathways are direct substitution (with inversion or retention of configuration), rearrangement (combined with substitution and inversion of configuration at both of the centres involved) and elimination. Based on the assumption of cyclic transition states or transient intermediates (formed through participation of neighbouring groups), far-reaching mechanistic generalisations were made. On this basis, isolated examples from the literature, which are not in accordance with these generalisations, are specifically brought to attention. Results from the recently introduced reaction of safe and easy to handle N-F fluorinating agents with glycals are also reported. This approach allows the simple and stereoselective access to a series of 2-deoxy-2-fluoro aldopyranoses, as well as the synthesis of various C-1-substituted derivatives by an easy one-pot reaction. However, the same method applied to furanoid glycals is rather poor with respect to stereoselectivity. Finally, considerations on the importance of fluorine-specific reactions of the S(N)-type in related fields of organic synthesis are made.

A novel direct route to 2-deoxy-2-fluoro-aldoses and their corresponding derivatives

Abstract A new type of reactive N-(2-deoxy-2-fluoro-glycosyl) compound is formed by regioselective syn-addition of the electrophilic N-F reagent Selectfluor™ to glycals. By subsequent treatment with nucleophiles, 2-deoxy-2-fluoro-aldoses and various C-1-substituted derivatives thereof are easily accessible. Furthermore, the reaction with D-galactal and D-arabinal proceeds stereoselectively, thus allowing the synthesis of 2-deoxy-2-fluoro-D-galactose- and -D-arabinose-derivatives in multi-gram quantities.

Reaction of acetyl hypofluorite with pyranoid and furanoid glycals

Abstract The regiospecific syn -addition of acetyl hypofluorite to glycals derived from pentopyranoses led to mixtures of stereoisomers. Stereospecific reactions occurred with furanoid glycals, the direction of addition being governed by the nature of the substituent at C-3. Whereas a benzyloxy group caused attack from the opposite, less-hindered face of the double bond, a hydroxyl group induced addition from the same side. From these reactions, 2-deoxy-2-fluoro derivatives of β- d -arabino-, α- d -ribo-, β- d -lyxo-, and α- d -xylo-pyranose as well as β- d -manno-, α- d -gluco-, α- d -ribo-, and β- d -arabino-furanose were obtainedl their 1 H-, 13 C-, and 19 F-n.m.r. data are given.

Reactions of D-Glucofuranurono-6,3-Lactone⋆

Publisher Summary This chapter discusses the reactions of D-glucofuranurono-6,3-lactone as they have been the subject of extensive investigations. Fundamentally, D-glucofuranurono-6,3-lactone contains the 2,6-dioxabicyclo [3.3.0]octane structure. The chapterdescribes its properties. D-glucofuranurono-6,3-lactone halides exhibit certain properties, such as (1) thermodynamic and solvolytic stability decreases in the series: fluoride, chloride, bromide, (2) 2,5-Di-O-acetyl-D-glucofuranosylurono-6,3-lacton halides are less stable than their 2,5-di-O-benzoyl or their 2-O-acetyl-5-O-benzoyl counterparts, (3) β-D-Glucofuranosylurono-6,3-lactone chlorides are subject to alcoholysis, with formation of alkyl β-D-glucofuranosidurono-6,3-lactones; under the same conditions the α-D-anomers are nonreactive, (4) like methyl 2,3,4-tri-O-acetyl-β-D-glucopyranosyluronate chloride,2,5-di-O-acyl- β-D-glucofuranosylurono-6,3-lactone chloride are quite resistant to anomerization. Furthermore, the reaction of per-O-acylated D-glucosyl bromides and chlorides with alcohols by heterogeneous, or homogeneous, base catalysis is commonly used for the preparation of D-glucosides. By an SN2 type of mechanism under Koenigs-Knorr conditions, α-D-glucopyranosyl halides form β-D-glucopyranosides, which are also obtained from the “unstable” β -D-glucopyranosyl chlorides through neighboring group participation.

3-desoxyhex-2-enono-1,4-lactone aus D-hexofuran(osid)- urono-6,3-lactonen☆

Abstract The yield of 2- O -benzyl-3-deoxy- L - threo -hex-2-enono-1,4-lactone by reaction of 5- O -benzyl-1,2- O -isopropylidene-α- D -glucofuranurono-6,3-lactone with sodium borohydride was improved by variation of the aprotic dipolar solvent and temperature. The general validity of this elimination—reduction reaction was ascertained by conversion of eleven other D -hexofuran(osid)urono-6,3-lactones into various 3-deoxy-hex-2-enono-1,4-lactones by treatment with sodium borohydride in hexamethyl phosphoric triamide.

Studies on the Reaction of D-Glucal and its Derivatives with 1-Chloromethyl-4-Fluoro-1,4-Diazoniabicyclo[2.2.2]Octane Salts

ABSTRACT The reaction of D-glucal and its derivatives with the electrophilic N-F-fluorination reagents F-TEDA tetrafluoroborate and triflate was studied by means of 19F NMR spectroscopy. In all cases mixtures of 2-deoxy-2-fluoro-D-gluco- and -D-mannopyranose derivatives were formed, the ratio of which was dependent on the nature of the O-protecting groups. Concerning the products arising from the direct addition of reagents across the double bond, the D-gluco-configured compounds (13-20) generally showed higher hydrolysis rates than their D-manno-counterparts (21-28). Product separation was only achieved when single anomers (e.g., 2,4-dinitrophenyl glycosides 29e/37e and disaccharidic fluorides 35d/43d) or per-O-acetates (e.g. 29f/37f) were formed.

Acetyl Migration in Partially Acetylated D-Glucopyrano-Sides and Acylamidohexopyranosides

Abstract O-4-O-6 Acetyl migrations in partially O-acetylated 2- and 3-acylamidodeoxyhexopyranosides, including derivatives of kanamycin A, were found to be particularly suited to allow the regiospecific accessibility of their respective C-4 OH groups. Partially O-acetylated d-glucopyranosides, compared to the substrates above, showed slightly different aptitudes of migration. However, all O-4-O-6 migrations investigated proved to be irreversible under the conditions applied.

Simultaneous detection of different glycosidase activities by 19F NMR spectroscopy.

A fast method for the simultaneous detection of different glycosidolytic activities in commercially available enzyme preparations and crude culture filtrates was found in using, as substrate, a mixture of different glycosyl fluorides and 19F NMR spectroscopy as a screening technique. Accompanying studies regarding the hydrolytic stability of these fluorides in various buffer systems, as well as conditions of their long-term storage, were carried out. A simple procedure for the preparation of beta-D-mannopyranosyl fluoride in gram quantities is given.

Synthesis of fluorinated kanamycin A derivatives

Abstract Replacement of OH-5 and/or OH-6″ by fluoride in kanamycin A; no substitution of OH-4″ but inversion of configuration when using DAST.

The stereochemical course of the reaction mechanism of trehalose phosphorylase from Schizophyllum commune

Phosphorolysis of α,α‐trehalose catalyzed by trehalose phosphorylase from the basidiomycete Schizophyllum commune proceeds via net retention of anomeric configuration and yields α‐d‐glucose 1‐phosphate and α‐d‐glucose as the products. In reverse reaction, only the α‐anomers of d‐glucose 1‐phosphate and d‐glucose are utilized as glucosyl donor and acceptor, respectively, and give exclusively the α,α‐product. Trehalose phosphorylase converts α‐d‐glucose 1‐fluoride and phosphate into α‐d‐glucose 1‐phosphate, a reaction requiring the stereospecific protonation of the glucosyl fluoride by a Brønsted acid. The results are discussed with regard to a plausible reaction mechanism of fungal trehalose phosphorylase.