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Oxidation of the aldoses (Ald) d -glucose, d -allose, d -mannose, d -galactose, 6-deoxy- d -galactose ( d -fucose) and 2,6-dideoxy- d - ribo -hexose (digitoxose) by Cr VI yields the aldonic acid and Cr 3+ as final products when an excess of sugar over Cr VI is used. The redox reaction occurs through Cr VI →Cr III and Cr VI →Cr V →Cr III paths. The rate laws for the Cr VI and Cr V oxidation reactions are expressed by: −d[Cr VI ]/d t = k H [Ald][Cr VI ] and −d[Cr V ]/d t = k b K b [Ald][Cr V ]/(1+ K b [Ald]), where k H , k b and K b are the kinetic parameters independent of the [Ald] and [oxidant], and the relative aldoses reactivity with both Cr VI and Cr V is 2,6-dideoxy- d - ribo -hexose> d -galactose> d -allose> d -glucose≈6-deoxy- d -galactose, at 33 °C. Intermediate sugar alkoxide radicals could be trapped with 5,5-demethyl-1-pyrroline N -oxide (DMPO) and observed by electron paramagnetic resonance (EPR) as a multiline signal at g =2.003. Cr V is formed in a rapid step by the reaction of the sugar radical with Cr VI . The substrate is oxidised at a comparable rate by Cr VI and Cr V , especially at higher [Ald], and the reduction of Cr VI occurs concurrently with Cr V . The EPR spectra show that five- and six-coordinate oxochromate(V) intermediates are formed, with the aldose and/or the aldonic acid acting as bidentate ligands. Penta-coordinate Cr V species are present at any [H + ], whereas hexa-coordinate ones require stronger acid conditions.

6-Deoxy-6- C -sulfo- d -glucopyranose (sulfoquinovose) has been prepared and characterised as its brucinium and potassium salts. The bis-cyclohexylammonium salt of its aldonic acid, 6-deoxy-6- C -sulfo- d -gluconic acid, has also been obtained. Their oxidation by sodium periodate gives 2-sulfoacetaldehyde.

Treatment of a solution of 3-deoxy- d -glycero- d -galacto-non-2-ulosonic (KDN) in 11 N aqueous hydrochloric acid with an excess of ethanethiol gave in 52% yield the diethyl dithioacetal of the corresponding 1,4-lactone, which was further characterized as its peracetate. With 1,3-propanedithiol, only one thiol function reacted and the product, isolated in 18% yield as its peracetate, was a vinyl thioether of the α,β-unsaturated 1,4-lactone. The methyl ester methyl β-glycopyranoside derivative of KDN could be converted to the 8,9-isopropylidene ketal 7 (69%). Conditions were found which allow selective silylation at C-4 with tert-butylchlorodimethylsilane, giving the 4-O-tert-butylsilyl derivative in 91% yield Heating it with bis(tributyltin) oxide afforded the 1,7-lactone with inversion of the ring conformation. Lithium aluminium hydride reduction of 7 afforded the corresponding methyl non-2-ulopyranoside, which was converted to the 1,4-bis(silyl) ether. Bromination of 1,5-anhydro-2-deoxy- d -arabino-hex-1-enitol in aqueous solution at 0°C with N-bromophthalimide gave a mixture of bromodeoxy hexoses from which 2-bromo-2-deoxy- d -mannose was isolated in 60% yield by crystallization. Its incubation with pyruvate in the presence of sialyl aldolase gave 5-bromo-3,5-dideoxy- d -glycero- d -galacto-non-2-ulosonic acid 16 in 70% yield.

2,3,4,6-Tetra- O -benzyl- d -glucopyranose, 2,3,5-tri- O -allyl- d -ribofuranose, 2,3,5-tri- O -allyl- and -tri- O -benzyl- d -arabinofuranose, and 2-deoxy-3,5-di- O -allyl- d - erythro -pentofuranose were oxidized to their corresponding lactones 6–10 by dimethyl sulfoxide activated by oxalyl chloride, pyridinium dichromate in the presence of molecular sieves and acetic acid, and tetra- n -propylammonium tetra-oxoruthenate(VII) using 4-methylmorpholine N -oxide as cooxidant. With the latter reagent, analytically pure lactones were obtained in 83–98% yield. A multistep preparation of 3,4,6-tri- O -benzyl-2-deoxy- d - arabino -hexono-1,5-lactone ( 14 ) from 3,4,6-tri- O -benzyl-1,5-anhydro-2-deoxy- d - arabino -hex-1 enitol (65% overall yield) is described.

A series of 3-C-alkyl-2,3-dideoxy-5-O-trityl-D-erythro-pentono-1,4-lactones were detritylated. The resultant free-hydroxy compounds were converted to their respective 2-C-alkyl-2,3-dideoxy-alpha,beta-L-glycero-tetrurono-1,4-lactones (L-sugar numbering) in a one-vessel reaction sequence of (a) conversion of the lactones to their aldonic acid sodium salts, (b) cleavage of the resulting aldonates with sodium metaperiodate, and (c) acidification, followed by acetylation, to give the title compounds. The unsubstituted tetrurono-1,4-lactones were inhibitory toward L1210 leukemia cells at concentrations in the 10(-4) M range.

The anomeric d -fructopyranosyl and l -sorbopyranosyl cyanides have been prepared via reaction of the respective 2-O-acetyl-1,3,4,5-tetra-O-benzoyl derivatives with BF3-trimethylsilyl cyanide in nitromethane. Configurations of the products at the tertiary center were assigned on the basis of rotational comparisons, 1H NMR data, and, in the case of β- d -fructosyl cyanide, by an X-ray structural analysis. From the conformational preferences of the 2-epimers — the cyano group invariably adopts an axial disposition entailing the 5C2 conformation for the β- d -fructo and α- l -sorbo cyanides versus the alternative 2C5 form for the α- d -fructo and β- l -sorbo anomers — the anomeric effect of a cyano group may be assessed to be of the same order of magnitude as that exerted by an acyloxy function.

A new approach towards simple aldonic acid derivatives starting from the corresponding aldoses via the 2-acetamido-2-deoxy formazans resulted in the synthesis of 2-acetamido-2-deoxy- d -galactono-1,4-lactone (8), and its 6-deoxy (11) and 6-azido-6-deoxy (14) analogues on treatment with trifluoroacetic acid. The five-membered ring structure of the lactones and that of the intermediate lactone phenylhydrazone (7) was proved by 1H and 13C NMR studies, including deuterium-induced differential isotope shift (DIS) measurements. With sodium borohydride, lactones 8 and 11 were converted into 2-acetamido-2-deoxy- d -galactitol (15) and its 6-deoxy analogue (17), respectively.

Acyclic trans -2,3-unsaturated aldoheptonate derivatives ( 1–9 ) obtained from d -aldopentoses by Witting chain-extension served as dienophiles for a detailed comparative study of their asymmetric Diels-Alder cycloaddition with cyclopentadiene. Cycloaddition under uncatalyzed thermal conditions gave mixtures of the four possible stereoisomeric norbornene adducts. The endo:exo ratios and the diastereofacial selectivities in the formation of the adducts were determined by NMR spectroscopy and by chemical transformations. The quantitative distribution of adducts as a function of stereochemistry of the dienophile is discussed.

A convenient preparative route is described for 3-deoxyaldulosonic acids. Glycal precursors are oxidatively converted into 2-deoxyaldonolactones, which react with 1,3-dithian-2-yl anion to afford 1,3-propanediyl dithioacetals of higher 3-deoxyaldosuloses. Deprotection with mercuric salts in wet or dry alcohols gave high yields of the corresponding alkyl aldulosonates. Preparative reaction conditions were optimized and the anomeric configurations of the ketopyranose products were established by 13C NMR.

Reaction of methyl 2,6-anhydro-2,3-dideoxy- d -manno-2-octenoate 1 with 3-chloroperoxybenzoic acid gave the 2,3-anhydro derivative 2, which was converted into the per-O-acetylated anomeric methyl glycosides of d -glycero- d -galacto-2-octulopyranosylonic acid in good yield. Subsequent inversion of the configuration at C-3 and deprotection afforded sodium (methyl β- d -glycero- d -talo-2-octulopyranosid)onate. Alternatively, 2 was transformed into methyl (α- d -glycero- d -talo-2-octulopyranosyl bromide)onate derivatives. Reaction with methanol or allyl 2-acetamido-2-deoxy-3,4-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-β- d -glycopyranoside, promoted by silver triflate, gave good yields of the corresponding orthoester derivatives. Me3Si triflate-catalyzed orthoester rearrangement and removal of the protecting groups afforded sodium O-(methyl α- d -glycero- d -talo-2-octulopyranosid)onate and the disacchanide, allyl O-[sodium (α- d -glycero- d -talo-2-octulopyranosyl)onate]-(2 → 6)-2-acetamido-2-deoxy-β- d -glucopyranoside in high yield.

2-Amino-2,4-dideoxy-4-fluoro- and 2-amino-2,4,6-trideoxy-4, 6-difluoro-D-galactose, and 2-amino-2,4-dideoxy-4-fluoro- and 2-amino-4-deoxy-4, 4-difluoro-D-xylo-hexose were synthesized, as potential modifiers of tumor cell-surface glyco-conjugate, from benzyl 2-acetamido-3-O-benzyl-2-deoxy-4, 6-di-O-mesyl-alpha-D-glucopyranoside and benzyl 2-acetamido-3, 6-di-O-benzyl-2-deoxy-4-O-mesyl-alpha-D-glucopyranoside, which were converted into the corresponding 4,6-difluoro-2,4, 6-trideoxy and 2,4-dideoxy-4-fluoro derivatives. Benzyl 2-acetamido-2-deoxy-4-O-mesyl-alpha-D-galactopyranoside and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-xylo-hexo-4-ulopyra noside were treated with diethylaminosulfur trifluoride to give 2-amino-2,4-dideoxy-4-fluoro-D-glucose and 2-amino-2,4-dideoxy-4, 4-di-fluoro-D-xylo-hexose derivatives, respectively, to give after deprotection the target compounds. Several of the peracetylated sugar derivatives inhibited L1210 tumor-cell growth in vitro at concentrations of 1-5 10(-5) M. The peracetylated derivative of 2-amino-2,4-dideoxy-4-fluoro-D-galactose inhibited protein and glycoconjugate biosynthesis, and also exhibited antitumor activity in mice with L1210 leukemia.

Enantiospecific syntheses of methyl 2,3,4-trideoxy-α- d - and -β- d -glycero-hexopyranoside (10 and 11) methyl α- d - and β- d -amicetopyranoside (24 and 25), (2S)-1,2-hexanediol (36), (2S)-1,2,6-hexanetriol (37), and some derivatives thereof from d -glucono-1,5-lactone are described.

Crystallization of C 30 H 34 O 11 N 2 in space group P2 1 with lattice parameters a=845.4, b=43.83.3, c=989.5A, β=114.82°, the final R value is 0.062.

The degradation of l -ascorbic acid in aqueous solutions by ultrasound and ionising radiation was more extensive in the presence than in the absence of air. The primary products were l -erythro-2,3-hexodiulosonic acid, cis- and trans- l -glycero-4-hexulos-2-enonic acid; the secondary products were 2-pentulosonic acid, 4-pentulos-2-enonic acid, tetronic acid, and glyceric acid; and the tertiary product was tetraric acid. The formation of products with less than six carbon atoms was especially effective during irradiation in the presence of air. A mechanism for the degradation of l -ascorbic acid by sonolysis and radiolysis is proposed.

N-Octylamides of diastereomeric gluconic and gulonic acids form molecular aggregates of extremely different curvature, namely helical micellar rods with a diameter of 4 nm and planar bilayers. In the crystal structure of the gulonamide compound, symmetric “tail-to-tail” bilayer sheets are observed, whereas the gluconamide derivative (whose crystal structure was determined previously) forms an unusual “head-to-tail” arrangement. These differences are unexpected because both diastereomers contain one pair each of syn- and anti-oriented hydroxyl groups in 1,3-positions of the extended aldonic acid chains. The experimental results are explained by the occurrence of hydrogen-bond patterns between hydroxyl groups, either within one crystal sheet or hydrophobic bilayer (gluconamide) or between the end groups of neighboring sheets (gulonamide).

Application of the Keck C -allylation of organic halides to 2-bromo-2-deoxy- d -arabinolactone resulted in the formation of mixtures of 2- C -allyl lactones. The stereochemical preferences observed were dictated by the nature of vicinal and remotely placed substituents in the lactone.

2,4-O-Benzylidene-L-xylose was converted via a Wittig reaction into Z-2,4-O-benzylidene-5,6-dideoxy-6-C-(2,4-dichlorophenyl)-D-xylo-hex-5-++ +enitol (17), which, on hydrogenation, gave 5,6-dideoxy-6-C-(2,4-dichlorophenyl)-D-xylo- hexitol (33). tert-Butyldimethylsililation of the primary hydroxyl group of 33, followed by 4-methoxybenzylation, and desilylation afforded 5,6-dideoxy-6-C-(2,4-dichlorophenyl)-2,3,4-tri-O-(4-methoxybenzyl)-D-xyl o- hexitol (54). A Mitsunobu-type reaction of 54 replaced HO-1 by cyanide to give, after hydrolysis and hydrogenolysis, 2,6,7-trideoxy-7-C-(2,4- dichlorophenyl)-D-xylo-heptono-1,4-lactone (55). Mesylation of 33 and then acetylation gave 2,3,4-tri-O-acetyl-5,6-dideoxy- 6-C-(2,4-dichlorophenyl)-1-O-methanesulfonyl-D-xylo-hexitol (63), which was converted via its 1-thiobenzoate into bis[1,5,6-trideoxy-6-C-(2,4-dichlorophenyl)-D-xylo-hexitol] 1,1'-disulfide (65). Acetylation of 65, followed by permanganate oxidation and deacetylation, afforded sodium 6-(2,4-dichlorophenyl)-D-xylo- 2,3,4-trihydroxy-hexanesulfonate (67). Both 57 (obtained from 55 by hydrolysis with NaOH) and 67 are weak inhibitors of HMG-CoA reductase.

In recent years, methods for the preparation of C-glycosyl compounds have become increasingly important in synthetic organic chemistry. These compounds are useful as subunits for the synthesis of biological active products’ and as potential enzyme inhibitors’. Significant attention has been focused on the development of new routes to prepare functionalized C-glycosyl compounds that are synthetic precursors of more complex C-glycosyl compounds. The starting materials can be furanose or pyranose carbohydrates, the main problem being the stereoselective introduction of a functionalized carbon atom at C-l. A widely used procedure to obtain carbon-carbon bonding at the anomeric position of carbohydrates was first reported by Zhdanov ef al. 3 This two-step procedure involves the formation of an unsaturated, open-chain intermediate, followed by a cyclization leading to the expected C-glycosyl compound. The first step is a Wittig reaction with protected furanose and pyranose hemiacetals. When stabilized ylides are used4, subsequent cyclization of the unsaturated intermediate may occur by treatment with bases or, sometimes, spontaneously. But when the Wittig reaction takes place with unstabilized ylides, the cyclization can be obtained by the iodoor mercuro-cyclization process’. It should be noted that C-glycosyl compounds can be synthesized in the same way when phosphonates are used instead of phosphorane$. Lastly, although stereoselective routes exist for both C-aand /I-glycosyl compounds, they mainly lack a general application. Stereoselectivity indeed depends on carbohydrate structures, ylides, and solvents. In the case of 2,3,4,6-tetra-O-benzyl-a,/?-D-glucopyranose (l), Nicotra et al.’ have observed an abnormal reaction of (carbethoxymethylene)triphenylphosphorane leading solely to a diene. The same elimination by Wittig reaction was observed for 3,4,6-tri-O-acetyl-2-O-benzyl-a&D-glucopyranose and partial elimination for 2,3,4,6-tetra-U-acetyl-a&D-glucopyranose. These abnormal reactions led Allevi et af.6 to use a Wittig-Horner reaction with 1 and sodium triethylphosphonoacetate

New pyrazoline acyclonucleosides have been prepared by 1,3-dipolar cycloaddition reactions of diazoalkanes to derivatives of d-galacto-oct-2-enonate and d-galacto-non-3-enulose. The reactions were highly regio- and stereo-selective, and single isomers were obtained in good yields. A tautomeric equilibrium between the 1- and 2-pyrazoline structures was observed for some of the isomers in solution.

Treatment of d -glucono-1,5- or d -mannono-1,4-lactone with anhydrous hydrogen fluoride catalysed by formic or acetic acid yields 3,6-anhydro- d -glucono- and - d -mannono-1,4-lactone, respectively. Similarly, d -mannitol is converted into 1,4-anhydro- d -mannitol and subsequently into the 1,4:3,6-dianhydride, whereas d -glucitol forms exclusively the 3,6-anhydride and, on further reaction, 1,4:3,6-dianhydro- d -glucitol. d -Glucose and 2-acetamido-2-deoxy- d -glucose are also converted into the corresponding 3,6-anhydrides by reaction with hydrogen fluoride and formic acid. 13 C-N.m.r. spectroscopy indicates that the reactions involve intermediate dioxolanylium ions.

Syntheses of 2-deoxy- d - arabino -hexitol ( 1 ), d -rhamnitol ( 2 ), 1,2-dideoxy- d - arabino -hexitol ( 3 ), 2,3-dideoxy- d - erythro -hexitol ( 4 ), and some derivatives thereof are described. These compounds were obtained by reductive sequences on various compounds formed from methyl 3,4:5,6-di- O -isopropylidene- d -gluconate ( 9 ).

Synthese de 3-[per-O-acetyl-L-galacto-(ou D-gluco-) pentitolyl]-6-phenyl-(ou 6-benzyl) 1,2,4-Triazolo [3,4-a] phtalazine et de 3-[per-O-acetyl-D-glycero-D-gulohexitolyl] 1,2,4-Triazolo [3,4-a] phtalazine a partir de la reaction d'1-hydrazino (ou 1-chloro) phtalazine (pouvant etre benzyle ou phenyle) avec soit les chlorures, hydrazides ou lactones d'acides aldoniques

Reactions between Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) and d -xylose, d -glucose, and d -galactose gave mainly 3,6-anhydro-1,4-lactones together with α,β-unsaturated-1,4-lactones. The preparation of 3,6-anhydro-1,4-lactones having the d - xylo , d - gluco , and d - galacto configurations is described.

The crude product of deamination of the commercially available L-homoserine was acetylated and the 2-O-acetyl-3-deoxy-L-glycero-tetronolactone (18) formed was used to N-acylate methyl perosaminide (methyl 4-amino-4,6-dideoxy-alpha-D-mannopyranoside, 12) and its 2,3-O-isopropylidene derivative. The major product isolated from the reaction was the crystalline methyl 4-(4-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-alpha-D-+ ++mannopyranoside (1, 70-75%) resulting from acetyl group migration in the initially formed 2'-O-acetyl derivative. O-Deacetylation of 1 gave the title amide 2. Compound 2, obtained crystalline for the first time, was fully characterized, and its crystal structure was determined. Deoxytetronamido derivatives diastereomeric with 1 and 2, respectively, were obtained by the acylation of 12 with 2-O-acetyl-3-deoxy-D-glycero-tetronolactone (prepared from D-homoserine), and subsequent deacetylation. Structures of several byproducts of the reaction of 12 with 18 have been deduced from their spectral characteristics. Since these byproducts were various O-acetyl derivatives of 2, the title compound could be obtained in approximately 90% yield by deacetylating (Zemplen) the crude mixture of N-acylation products, followed by chromatography.

The diethyl dithioacetals of d -altrose, d -idose,, and d -talose were used to synthesise the respective O-benzyl aldehydo-sugars as intermediates for the synthesis of 3-deoxy- d -glycero- d -gluco / manno-3-deoxy- d -glycero- l -gulo / ido-, and 3-deoxy- d -glycero- l -allo / altro-octonate derivatives, respectively. After reduction and deprotection, the respective 3-deoxyoctitols were obtained. For the synthesis of 3-deoxy- d -glycero- l -galacto / talo-octitol, 2,3:5,6-di-O-isopropylidene- d -gulono-1,4-lactone was transformed by reduction and selective oxidation of C-1 to the aldehydo- d -gulose, from which the 3-deoxy- d -glycero- l -galacto / talo-octonate was synthesised. Carboxyl- and carbonyl-reduction and deprotection gave the 3-deoxyoctitol. The 3-deoxyoctitols were characterised by GLC and GLC-MS in the acetylated and methylated form. The data presented here and the data published earlier [T. Krulle, O. Holst, H. Brade, and R.R. Schmidt, Carbohydr. Res., 247 (1993) 145–158] showed that methylated 3-deoxy- d -glycero- d -galacto / talo-octitol can be distinguished by GLC from the other 3-deoxy- d -octitols and thus allows the identification of the manno configuration of 3-deoxy- d -manno-octulosonic acid (Kdo) in natural products such as the lipopolysaccharides of different Gram-negative bacteria, where Kdo is a generally occurring constituent.

A series of 3- C -alkyl- (and 3- C -phenyl-) 2,3-dideoxy- d - erythro -pentono-1,4-lactones, compounds which are important in the synthesis of modified nucleosides and antibiotic sugars, were synthesized from d -ribonolactone. By a route that proceeded via 5- O -protected d -ribonolactone, 5- O -protected 2,3-dideoxy- d - glycero -pent-2-enono-1,4-lactones were synthesized and reacted with R 2 CuLi or a complex PhSCu(RMgBr) n to give respectively the 3- C -alkyl or 3- C -phenyl compounds. Details of the preparation of the O -protected intermediates, as well as the selection of the organometallic reagents, are provided.

Each of the four d -aldopentoses (1–4) reacts in the unprotected form with Ph3PCHCO2Me (5) in THF to give stereoslectively the coresponding trans-α,β-unsaturated C7 Wittig adducts, isolated as the corresponding 4,5,6,7-tetraacetates (7–10) or 4,5:6,7-di-O-isopropylidene derivatives (11–14). Concurrently formed are also bicyclic, 1,4-lactone derivatives, isolated as their 5,7-diacetates (15–18) or 5,7-O-isopropylidene derivatives (19), arising through intramolecular Michael addition from the initial acyclic adducts. Formation of the cyclized products is suppressed by incorporation of Cu(OAc)2 in the reaction mixture, permitting preparative isolation of the hept-3-enonate derivatives 7–10, useful as dienophiles in Diels-Alder carbocyclizations with chirality transfer. Optimized yields were 25% ( d -ribo), 50% ( d -arabino), 49% ( d -xylo), and 61% ( d -lyxo). Under Cu(OAc)2-catalyzed conditions, the formation of small proportions of 3,7-anhydroheptonic acid esters (21 and 23) was observed in the d -arabino and d -xylo series, but not with the other two pentoses.

Sequential reaction of 2,3,4,6-tetra-O-benzyl-D-glucopyranose (7) with butyllithium and 2-[2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D- arabinonoyl]thio-3-nitropyridine (6) at -78 degrees gave 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl 2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D-arabinonate+ ++ (8; 71%, alpha:beta greater than 50:1). Ester carbonyl methylenylation, desilylation, and iodoetherification in the presence of silica gave 3,4,6-tri-O-benzyl-1-deoxy-1-iodo-(2,3,4,6-tetra-O-benzyl-alpha-D- glucopyranosyl)-beta-D-fructofuranoside (15; 44%, alpha:beta greater than 50:1). This neopentylic iodide 15 was converted into sucrose (1;80%) by free-radical substitution using TEMPO (24) followed by sodium-ammonia reduction, acetylation, and Zemplén methanolysis.

Polyamides, polyesters, and polyurethanes have several biomedical applications (surgical sutures, membranes, superficial coverings, and drug-delivery systems). As a first step in the synthesis of polyamides from sugar derivatives, we now report the preparation of derivatives of 6-amino-6-deoxy-o-gluconic acid that are precursors of bifunctional monomers for linear polycondensations. Various 6-amino-6-deoxy-D-aldonic acids and some of their derivatives have been described’. 6-Amino-6-deoxy-2,3,4,5-tetra-O-methyl-o-gluconic acid (1) has been prepared2 (14% overall yield) in six steps from 6-azido-6-deoxy-1,2-O-isopropylidene-a-o-glucofuranose. A more convenient synthesis starts from methyl a-D-glucopyranoside (7), selective 6-tosylation of which followed by treatment with sodium azide in N,N-dimethylformamide gave S3. The azido group was not reduced to an ammo group until the last step because of its stability towards acidic and weakly basic conditions, and also against oxidation4. Treatment of 8 with methyl iodide-potassium hydroxide in methyl sulphoxide gave the tri-O-methyl derivative 9, acid hydrolysis of which followed by oxidation5 with acetic anhydride-methyl sulphoxide gave 6-azido-6-deoxy-2,3,4-tri-O-methyl-p-glucono1,Slactone (11). Opening of the lactone ring in 11 and methylation of HO-5 was carried out with methyl iodide-potassium hydroxide-tetrahydrofuran to give 6-azido-6-deoxy2,3,4,5-tetra-0-methyl-D-gluconic acid (2, 97%), characterised as the methyl ester 3. Hydrogenation of 2 in hydrochloric acid gave 6-amino-6-deoxy-2,3,4,5-tetra-Omethyl-D-gluconic acid (1, 30% from 71, which was transformed into the N-(tertbutoxycarbonyl) pentachlorophenyl (5) and p-nitrophenyl (6) esters suitable for polymerisation after removal of the N-protecting groups.

Evidence for the anomeric configurations and attachment sites of 3-deoxy-D-lyxo-2-heptulosaric acid (DHA) and apiosyl residues has been obtained through the characterization of two oligoglycosyl fragments isolated from rhamnogalacturonan II (RG-II). One of the oligoglycosyl fragments, a pentaglycosyl aldonic acid generated by Smith degradation of RG-II, was composed of four D-galactopyranosyluronic acid residues, a DHA residue, and a threonic acid residue (derived from a D-galactopyranosyluronic acid residue). The structural analysis of the pentaglycosyl aldonic acid established the beta-D-configuration for the DHA residue. Furthermore, it established that a previously identified diglycosyl side chain, 5-O-(beta-L-arabinofuranosyl)-DHA was directly attached to O-3 of a D-galactopyranosyluronic acid residue in the backbone of RG-II. The second oligoglycosyl fragment, a peralkylated diglycosyl hex-1-enitol, was generated by hex-5-enose degradation of permethylated and carboxyl-reduced RG-II. The structure of the peralkylated diglycosyl hex-1-enitol, beta-L-Rhap-(1----3')-beta-D-Apif-(1----5)-hex-1-enitol++ +, was determined by a combination of glycosyl-linkage composition analysis and n.m.r. spectroscopy. The n.m.r. data indicated the beta-configuration for the D-apiosyl residue. The isolation and characterization of the diglycosyl hex-1-enitol also established that a previously identified heptaglycosyl side chain was directly attached to O-2 of a D-galactopyranosyluronic acid in the backbone of RG-II.

The title compounds, required for the identification of structural features of the Bordetella pertussis endotoxin, have been synthesised by condensation of benzyl 3-O-benzyl-2-deoxy-beta-L-erythro-pentopyranoside with 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl bromide and with 4,6-di-O-acetyl-2,3-O-carbonyl-alpha-D-mannopyranosyl bromide, respectively, thus affording the fully protected alpha- and beta-linked disaccharides 7 and 12. Hypoiodite oxidation of the reducing disaccharides 9 and 14, obtained by conventional deprotection of 7 and 12, yielded the title compounds.

2,3-Didehydro-2-deoxy- N -trifluroacetylneuraminic acid (5-trifluoroacetyl-Neu2en) ( 3 ) has been synthesised from Neu5Ac2en ( 1 ) by hydrazinolysis, to give Neu2en ( 2 ), followed by N -trifluoroacetylation. 2,3-Didehydro-2,3-dideoxy- d - glycero - d - galacto -2-nonulopyranosonic acid (Kdn2en, 8 ) and 5-azido-2,3-didehydro-2,3,5-trideoxy- d - glycero - d - galacto -2-nonulopyranosonic acid (5-azido-5-deoxy-Kdn2en, 9 ) have been prepared from the acetylated methyl esters of Kdn ( 4 ) and 5-azido-5-deoxy-Kdn ( 5 ) via Zemplen saponification. The behaviour of the above 2,3-didehydro-2-deoxysialic acids towards Vibrio cholerae sialidase has been investigated

Methyl D-pentofuranosides were prepared by Fischer glycosidation of the aldopentoses D-arabinose, D-lyxose, D-ribose, D-xylose, and 2-deoxy-D-erythro-pentose, and oxidized with O2 over a platinum oxide catalyst to give the corresponding methyl D-pentofuranosiduronic acids. After purification by anion-exchange chromatography, these glycosides were hydrolyzed to give the corresponding D-penturonic acids [D-arabinuronic acid (1), D-lyxuronic acid (2), D-riburonic acid (3), D-xyluronic acid (4), and 2-deoxy-D-erythro-penturonic acid (5)] in 80% yield based on the starting pentofuranoside. 1-13C-Substituted D-aldopentoses were used to prepare D-(1-13C)penturonic acids. Aqueous solutions of the 1-13C-substituted penturonic acids, studied over a range of pH values by 13C-n.m.r. spectroscopy, were found to contain alpha- and beta-furanoses, acyclic aldehyde and hydrate, and/or hydrated 2,5-lactone. The ratio of D-riburonic acid anomers was most sensitive to solution pH (alpha/beta = 0.49 and 1.2 at pH 1.9 and 4.9, respectively). The values of the 1H and 13C chemical shifts, and 1H-1H. 13C-1H, and 13C-13C spin-coupling constants, were determined by 1H-(300, 500, and 620 MHz) and 13C-(75 MHz) n.m.r. spectroscopy with the aid of 2-D 13C-1H chemical shift correlation maps, 2-D 1H-1H COSY data, and 13C substitution, and were compared to those determined previously for structurally-related furanose rings. Isomerization of the penturonic acids at pH 5.0 and 50 degrees gave the corresponding 4-pentulosonic acids.

The synthesis of the enantiomers of 6-epicastanospermine and of 1,6-diepicastanospermine from the enantiomeric gulonolactones is reported and the structure of the former is established as (1 S ,6 R ,7 R ,8 R ,8a R )-1,6,7,8-tetrahydroxyoctahydroindolizine. The inhibitory activities of the diastereomers against the amyloglucosidase-catalysed hydrolysis of p -nitrophenyl α- d -glucopyranoside were investigated, and the effects of 6-epicastanospermine and of 1,6-diepicastanospermine on 14 human liver glycosidases are reported.

1,5-Anhydro-3- O -benzyl-2,6-dideoxy-4- O -(3,4-di- O -benzyl-2,6-dideoxy-β- d - arabino -hexopyranosyl)- d - arabino -hex-1-enitol ( 17 ), which corresponds to the BC fragment of various orthosomycins, was prepared from phenyl 2,3-di- O -benzyl-6-deoxy-4- O -(3,4-di- O -benzyl-2,6-dideoxy-β- d - arabino -hexopyranosyl)-1-thio-β- d -glucopyranoside ( 16 ) by reductive lithiation. The synthesis of 16 involved a stereoselective coupling of phenyl 2,3-di- O -benzyl-6-deoxy-1-thio-β- d -glucopyranoside ( 9 ) and 1,2-di- O -acetyl-3,4-di- O -benzyl-6-deoxy-β- d -glucopyranose ( 14 ) followed by deoxygenation at C-2′. Glycosylation of methyl 2- O -benzyl-6-deoxy-4- O -methyl-β- d -galactopyranoside ( 25 ) with 3,4,6-tri- O -acetyl-2-deoxy-2-phthalimido-β- d -glucopyranosyl trichloroacetimidate, followed by deamination at C-2′, led stereospecifically to methyl 2- O -benzyl-6-deoxy-4- O -methyl-3- O -(3,4,6-tri- O -acetyl-2-deoxy-β- d - arabino -hexopyranosyl)-β- d -galactopyranoside ( 26 ). The 2-deoxy unit of 26 was then modified by consecutive axial introduction of a C-Me group at position 3′, protection of HO-3′, and deoxygenation at C-6′, in order to obtain methyl 3- O -(3- O -benzoyl-2,6-dideoxy-3- C -methyl-β- d - arabino -hexopyranosyl)-2- O -benzyl-6-deoxy-4- O -methyl-β- d - galactopyranoside ( 39 ), which corresponds to the DE fragment of orthosomycins. A glycosyloxyselenation-oxidation-elimination sequence was performed on 39 and either 1,5-anhydro-3,4-di- O -benzyl-2,6-dideoxy- d - arabino -hex-1-enitol ( 40 ) or 1,5-anhydro-3- O -benzyl-2,6-dideoxy-4- O -(3,4-di- O -benzyl-2,6-dideoxy-β- d - arabino -hexopyranosyl)- d - arabino - hex-1-enitol ( 17 ) to give the CDE tri- and BCDE tetrasaccharide fragments, respectively. Each fragment contained the spiro-ortholactone junction with an ( R ) configuration at the anomeric carbon atom of the C-unit.

Selective C-8 modifications of 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid ("2,3-dideoxy-beta-D-manno-2-octulosonic acid", 1a) were effected via the protected 8-hydroxy derivatives 2d and 2e. Swern oxidation of 2d and 2e gave the aldehydes 3a and 3b, respectively. Compounds 3a and 3b were converted into the oxime 13b and the O-methyloxime 13c derivatives, respectively. Methodology was developed for selective cleavage of the protecting groups of 13b and 13c to give the deprotected oxime 12m and the deprotected O-methyloxime 12n, respectively. Side chain-extended products were prepared from the aldehyde 3a utilizing Wittig methodology. The branched chain allylic amine 12p was prepared from 3a in a sequence the keys steps of which were preparation of the methyl ketone 19a using LiCuMe2, followed by Swern oxidation, methylenation of 19a using CH2I2-Zn-TiCl4 to give the alkene 19b, followed by Wohl-Ziegler bromination of 19b to give the allylic bromide 19c, and conversion of the latter to the allylic azide 19d. A number of the analogs showed significant activities vs CMP-Kdo synthetase. The most active of these was the side-chain extended alkene 12d, which proved second in activity only to the 9-amino analog (1c).

Kraft pulping of pine wood and treatment of guaran with alkali gave several O-α- d -galactopyranosylsaccharinic acids or related compounds, which were analysed by capillary g.l.c.-m.s. Of these compounds, twelve were identified and eight were new. The degradation of galactomannans by alkali is discussed.

The first synthesis of 2,5-anhydro-5-thio-D-allononitrile starting with L-lyxose, via a trifluoromethanesulfonic ester intermediate, has been accomplished. Methods have been developed to achieve a large-scale synthesis of 3,4,5,7-tetra-O-acetyl-2,6-anhydro-D-glycero-D-talo-heptononitrile (5). An improved procedure has been developed to synthesize 2,5-anhydro-3,4,6-tri-O-benzoyl-D-gulononitrile (9). The structures of 5 and the thioamide derivative from 9, 2,5-anhydro-3,4,6-tri-O-benzoyl-D-gulonothioamide, were confirmed by X-ray crystallographic analysis.

Trifluoroacetolysis of d -glucuronic acid and methyl α- d -glucopyranosiduronic acid resulted in an initial phase of degradation followed by stabilisation of the compounds as their 6,3-lactones. The methyl ester of methyl 4-O-methyl-α- d -glucopyranosiduronic acid was largely stable towards trifluoroacetolysis. Aldonic acids substituted at O-3 or O-6 were stable towards trifluoroacetolysis because of the formation of γ-lactones. Aldonic acids substituted at O-4, and incapable of forming γ-lactones, were converted into the trifluoroacetylated enol of 3-deoxy-2-hexulosonic acid. Treatment of the 3-deoxy-2-hexulosonic acid with mild base eliminated the substituent at O-4.

d -Glucono-1,5-lactone reacts with aroylhydrazines to give the corresponding 1-aroyl-2- d -gluconylhydrazines. Condensative cyclization of these compounds using triethyl orthoformate gave the corresponding 5-aryl-2-ethoxy-3- d -gluconyl-2,3-dihydro-1,3,4-oxadiazoles.

Electrophile-mediated cyclization of 3,4,6-tri- O -benzyl-1,2-dideoxy- d - arabino -hex-1-enitol with N -bromosuccinimide yielded primarily 2,5-anhydro-3,4,6-tri- O -benzyl-1-bromo-1-deoxy- d -glucitol ( 10 ). This apparently kinetically controlled reaction was of key importance in the successful synthesis of a phosphonate analog of β- d -arabinose 1,5-bisphosphate ( 1 ), namely, 2,5-anhydro-1-deoxy-1-phosphono- d -glucitol 6-phosphate ( 4 ), whith high stereoselectivity. By contrast, condensation of the sodium salt of tetraethyl methylenediphosphonate and 2,3,5-tri- O -benzyl- d -arabinose ( 7 ) gave a phosphonate compound slightly enriched in the 2,5-anhydro- d -mannitol (α) isomer. In the Wittig—Michael reaction of stabilized phosphoranes with 7 , the α isomer preponderated. Since equilibration of methyl 3,6-anhydro-4,5,7-tri- O -benzyl-2-deoxy- d - glycero - d - galacto - ( 33 ) and - d - gulo -heptonate ( 34 ) (5:1) resulted in a 1:1 α:β ratio, the preference for the 2,5-anhydro- d -mannitol (α) isomer probably reflects a kinetic bias. The carbomethoxy anomers were converted independently into the α and β carboxylate isosteres ( 5 and 6 , respectively) of d -arabinose 1,5-diphosphate. Empirical force field calculations (MMP2) and n.m.r. experiments were conducted on the pairs of diastereomers 9 and 10 , and 33 and 34 . The calculations predict that the α and β anomers of each pair have similar energies, differing by only 2.1 kJ/mol. Compounds 4, 5 , and 6 were evaluated for biological activity.

d -Glucose, d -mannose, and d -galactose gave in two steps the corresponding per-O-acetyl-2,6-anhydro-1-deoxy-1-nitroheptitols. Treatment with phosphorus trichloride in pyridine gave directly the corresponding 3,4,5,7-tetra-O-acetyl-2,6-anhydroheptononitriles (“glycopyranosyl cyanides”). The same treatment was applied to the 3,4,5-tri-O-acetyl-2,6-anhydro-1-deoxy-1-nitrohexitols, prepared from d -xylose, d -lyxose, l -arabinose, and d -ribose, and led to the corresponding 3,4,5-tri-O-acetyl-2,6,-anhydrohexononitriles in yields ranging from 65 to 80%. No anomerization was observed, thus allowing the preparation, in high yields, of cynanides having even the 1,2-cis configuration. The anhydronitriles were compared with other known examples of this class of compounds and conformational equilibria in solution determined by 1H-n.m.r. spectroscopy. A significant anomeric effect of the cyano group is doubtful. Instead, a stabilizing effect by the 1,3-diaxial arrangement of a cyano group and an acetoxy substituent seems to be present.

The 2,3:4,5- ( 8 ) and 2,4:3,5-di- O -isopropylidene ( 10 ) derivatives of d -mannitol have been prepared from 1,6-di- O -benzoyl- d -mannitol and their structures established by 13 C-n.m.r. spectroscopy. The 1,3-dioxane rings in 10 adopt a skew conformation and the sugar carbon chain in 8 is bent around the C-3-C-4 bond, as found by i.r. data and molecular mechanics calculations. Oxidation of 8 with pyridinium dichromate gave 2,3:4,5-di- O -isopropylidene- d -mannono-1,6-lactone ( 12 ).