Synthesis of O-α-L-Fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D-glucopyranose. The H-Blood Group Specific Trisaccharide

Abstract

Different reaction conditions were investigated for the preparation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (5). Compound 5 on reaction with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded the 4-O-substituted 2-acetamido-2-deoxy-β-D-glucopyranosyl derivative which, on O-deacetylation, gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-glucopyranoside (8). The trimethylsilyl (Me₃Si) derivative of 8, on treatment with pyridineacetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having an O-acetyl group selectively introduced at the primary position and Me₃Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol to afford benzyl 2-acetamido-4-O-(6-O-acetyl-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which on isopropylidenation gave the desired, key intermediate benzyl 2-acetamido-4-O-(6-O-acetyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (12). Reaction of 12 with 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide under catalysis by bromide ion afforded the trisaccharlde derivative from which the title trisaccharide was obtained by systematic removal of the protective groups. The structures of the final trisaccharide and of various intermediates were established by ¹H and ¹³C NMR spectroscopy.     

Synthesis and Reactivity of Benzyl 2-O-Trifluoromethyl-Sulfonyl- and Benzyl 3-O-Trifluoromethylsulfonyl-β-D-Ribofuranoside - The first Evidence of Trifluoromethyl-Sulfonyl (Triflyl) Migration in Carbohydrates

Abstract

Benzyl 2,5-di-O-(tert-bstvldimethvl)silvl-3-O-triflvl-β-D-ribofsranoside (13) underwent triflyl migration upon O-desilylation with triethylammonium hydrogen fluoride in tetrahydrofuran affording benzyl 2-O-triflyl-β-D-ribo-furanoside (7) in ca. 5% yield, together with three other products, benzyl 3-O-triflyl-β-D-ribofuranoside (17), benzyl 2-O-(tert-butyldimethyl)silvl-3-O-triflyl-β-D-ribo-furanoside (18) and benzyl 3-deoxy-β-D-glvceropento-furanos-2-uloside (16). In order to confirm the triflyl migration, a series of reactions were performed.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

An Improved Method for the Synthesis of 3.6-Di-O-Methyl-D-Glucose: Preparation of the Neo-Glycoprotein Containing 3,6-Di-O-Methyl-β-D-Glucopyranosyl-Groups

Abstract

3,6-Di-O-methyl-D-glucose, the non-reducing terminal sugar of the phenolic glycolipid-I, elaborated by Mycobacterium leprae, has been synthesized by a simple procedure and in high yield. 3-O-Methyl-D-glucose was converted to the corresponding benzyl glycoside and then tosylated to give benzyl 3-O-methyl-6-O-tosyl-β-D-glucopyranoside. Displacement of tosyl group with sodium methoxide followed by debenzylation afforded 3,6-di-O-methyl-D-glucose in high yield. Condensation of the acetobromo derivative of 3,6-di-O-methyl-D-glucose with 8-ethoxycarbonyloctanol gave 8-ethoxycarbonyloctyl 2,4-di-O-acety 1–3, 6-di-O-methy 1-β-D-glucopyranoside. This was then deacetylated, converted to hydrazide, and finally coupled to bovine serum albumin via the acyl azide intermediate. The neo-glycoprotein containing the 3,6-di-O-methyl-β-D-glucopyranosyl group is useful for serodiagnosis of leprosy.     

Synthesis of the Oligosaccharide Moieties of Musettamycin,Marcellomycin and Aclacinomycin A,Antitumor Antibiotics

Abstract

Condensation of benzyl 2,3,6-trideoxy-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (5) with 4-O-acetyl-3-O-benzyl-2,6-dideoxy-α-L-lyxo-hexopyranosyl bromide (10) carried out under Koenigs-Knorr conditions gave 12. Total deprotection of 12 and N-dimethylation at C-3 led to 17 while selective removal of the 4-O-acetyl group led to 13, a synthetic intermediate for preparing 24 and 33. Condensation of 13 with di-O-acetyl-L-fucal (18) or 4-O-acetyl-L-amicetal (25) in the presence of N-iodosuccinimide followed by hydrogenolysis of the C-2-I bond gave 20 and 27 respectively. The trisaccharide 24 then was obtained from 20 by the same sequence of reactions used to convert 12 into 17. After deacetylation and oxidation, this set of reactions also transformed 27 into 33.     

Synthetic Application of Partially Protected Fructopyranoses

Partial deacetonation of 1-O-benzoyl-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose (2) yielded the related 2,3-O-isopropylidene derivative (3) that was subsequently transformed into the corresponding 1-O-benzoyl-4,5-O-dibutylstannylene-2,3-O-isopropylidene-β-D-fructopyranose (4). Reaction of 4 with benzyl bromide proceeded with high regioselectivity to afford 1-O-benzoyl-5-O-benzyl-2/3-O-isopropylidene-β-D-fruc-topyranose (5) together with a small quantity of the 4-O-benzyl derivative (6). Oxidation of 5 gave the 4-oxo derivative (10) which was reduced to yield a mixture of 5 and its 4-epimer (11). Debenzylation of 11, followed by a debenzoylation reaction produced 2,3-O-isopropylidene-β-O-tagatopyranose (13). Aceto-nation of 13 yielded 1,2:3,4-di-O-isopropylidene-α-D-tagatofuranose (14). Structures and configurations of the above compounds were established on the basis of their analytical and spectroscopic data.     

Synthesis of Fluorinated Dienylic Stannanes Via the Wadsworth-Emmons Reaction

Geminal difluorination of dithiolane 9 affords bis benzyl ether 4b which is converted to beta-fluoroenals 3Z/3E. Reaction of these enals with the stannylmethyl Wadsworth-Emmons reagent 2 produces dienyl esters 14Z/14E which are converted to highly functionalized dienylic stannanes 1Z and 1E.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

Darstellung Von β-D-Olivosyl(1→3)-D-olivosiden Aus Mithramycin

Abstract

The benzyl glycoside 4 obtained from 2-bromo-2-deoxy-α-0-quinovosyl bromide 1, readily accessible by the dibromomethyl methyl ether reaction of 2, is deformylated to give the monohydroxy compound 5 which is used in glycosidation reactions. Treatment of 3 with dibromomethyl methyl ether results in the formation of the labile β-furanosyl bromide 7 and the cyrstalline pyranosyl bromide 8 in a ratio of 1:2, both of which are further characterized by their methyl glycosides 10 and 11, respectively. Action of dibromomethyl methyl ether at room temperature on the benzyl ether 6, conventionally prepared from 3, is shown to proceed initially to the glycosyl bromide 9. Compound 9 is cleaved to the 4-formyl-blocked pyranosyl bromide 12, and only after prolonged reaction time gives the pyranosyl halide 8. The glycosidation of the glycosyl bromide 1 with benzyl-4–0-benzyl-α-D-olivoside 13 in the presence of silver carbonate and silicate is a sluggish reaction and gives rather low yields of the β-and the α, l-3-linked disaccharides 15 and 16 in the ratio 3–4:1. With silver triflate the yield is improved to the 61% and the ratio 6:1 in favour of 15.

Further transformations lead to both the syrupy olivosyl olivosides 17. and 18. In a more favourable reaction sequence 1 is condensed with the alcohol component 5 and silver triflate as promoter and yields the crystalline β-(19) and the α, 1→3-linked disaccharides (20) in 92% and a ratio of 6.5: 1. By subsequent transformations the protected title tetradeoxy disaccharide 21 is obtained.     

Efficient Synthesis of E-Stilbenes

A convenient, high yield, method for the synthesis of E-stilbenes (2a-f and 3) is described starting from benzyl bromides (1a-f) using LDA.     

Nonreducing-Sugar Subunit Analogs of Bacterial Lipid a Carrying the Ester-Bound (3R)-3-(Acyloxy)Tetradecanoyl Group

Abstract

In order to elucidate further the relationship between the composition of the fatty acyl groups in the nonreducing-sugar subunit of bacterial lipid A and its biological activity, 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-4-O-phosphono-D-glucose [GLA-63(R, R) and GLA-64(R, R)], and 3-O-[(3R)-3-(acyloxy)tetradecanoyl]-2-deoxy-4-O-phosphono-2-tetradecanamido-D-glucose [GLA-67(R), GLA-68(R) and GLA-69(R)] have been synthesized. Benzyl 2-[(3R)-3-(benzyloxymethoxy)tetradecanamido]-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (5) and benzyl 2-deoxy-4,6-O-isopropylidene-2-tetradecanamido-β-D-glucopyranoside (6) were each esterified with (3R)-3-dodecanoyloxytetradecanoic acid (1), (3R)-3-tetradecanoyloxytetradecanoic acid (2) or (3R)-3-hexadecanoyloxy-tetradecanoic acid (3), to give 7-11, which were then transformed, by the sequence of deisopropylidenation, 6-O-tritylation and 4-O-phosphorylation, into a series of desired compounds.     

An Allylic Rearrangement Arising from Reaction of Fluoride Ion and A 3-Chloro, 4,5-Unsaturated Uronate Derivative

Reaction of methyl [benzyl 2-[(benzyloxycarbonyl)-amino]-3-chloro-2,3,4-trideoxy-β-L-threo-hex-4-enopyrano-sid]uronate,3,4-trideoxy-β-L-threo-hex-4-enopyranosidjuronate (7) with silver fluoride gave the 5-fluoro, 3,4-unsaturated uronate derivative 8, which, on treatment with methanolic ammonia, afforded the corresponding 5-meth-oxy, uronamide 9. The structures of 8 and 9 were confirmed by spectral data and by x-ray crystallographic analysis of 8. ¹H NMR spectroscopy parameters for 9 and its diastercomen 11 have been used to probe the conformational preferences in solution.     

Synthesis of 4-O-(α-L-Rhamnopyranosyl-D-Glucopyranuronic Acid

Abstract

Two approaches were used for the synthesis of 4-O-(α-l-rhamno-pyranosyl)-d-glucopyranuronic acid (1). Rhamnosylation of benzyl 6-O-allyl-2,3-di-O-benzyl-β-d-glucopyranoside (7), followed by deallylation, oxidation to uronic acid, and deblocking afforded 1. Alternatively, rhamnosylation of suitably protected d-glucuronic acid derivatives (25 and 26) gave the protected pseudoaldoBiouronic acid derivatives (19 and 30), which were deprotected. Rhamnosylations were performed in high stereoselectivity without neighbouring-group assistance using 2,3,4-tri-O-benzyl-1-O-trichloroacetimidoyl-α-l-rharnnopyranose (27) with tri-fluoromethanesulfonic acid catalysis.     

Synthesis of a Pentasaccharide Corresponding to the Antithrombin III Binding Fragment of Heparin

The synthesis of a protected pentasaccharide 27b corresponding to the antithrombin III binding region of heparin is presented. This pentasaccharide was prepared from two disaccharides (12c and 23) and a monosaccharide (1). The glucuronic acid containing disaccharide 12c was prepared from easily available monomers 6 and 7. Oxidation to the uronic acid was performed in the disaccharide stage. L-Idose derivative 16, prepared via a new route, was coupled with 1,6-anhydro derivative 17, oxidized and transformed into disaccharide 23. Coupling of 12c and 23 to tetrasaccharide 24a has been investigated. Better yields were obtained without collidine, the reason for which is explained. Coupling of 24b and 1 afforded the pentasaccharide 27b, protected with acetyl at the positions to be sulphated, benzyl at the other hydroxyl functions and azide at the 2-position of the glucosamine residues. Conversion of 27b into the sulphated pentasaccharide Ib can be performed according to published procedures.     

WEAK [BUT ATTRACTIVE] INTERACTION BETWEEN ALIPHATIC AND AROMATIC GROUPS/ CH…π COMPLEXATION/ ITS IMPLICATION IN CHEMISTRY AND BIOLOGY

Abstract

Evidence has been presented that Bu ^t group in l-phenylethyl t-butyl sulphide, sulphoxides, sulphone, carbinols (1) as well as in benzyl t-butyl sulphoxide (2) prefers to orient itself anti to Me and gauche to Ph group.     

An Unusual Behavior of Methyl or Benzyl 3-Azido-5-O-Benzoyl-3,6-Di-Deoxy-α-L-Talofuranoside with (Dimethylamino)Sulfur Trifluoride; Migration of the Alkoxyl Group from the C-1 to the C-2 Position

The reaction of methyl or benzyl 3-azido-5-0-benzoyl-3,6-di-deoxy-α-L-talofuranoside with (diethylamino)sulfur trifluoride (DAST) in toluene at 60°C resulted in the formation of 3-azido-5-0-benzoyl-3,6-dideoxy-2-0-methyl (or 2-0-benzyl)-3β-L-galactofuranosyl fluoride in good yield. In this reaction the alkoxyl group at C-1 migrated to the C-2 position and a fluorine atom entered into the C-1 position. The furanosyl fluoride was converted, via reduction of the azido group followed by N-trifluoroacetylation, acetolysis, and O-deacetylation, into 3,6-dideoxy-2-0-methyl-3-trifluoroacet-amido-L-galactopyranose (2-methoxy-Daunosamine derivative).     

A Facile Synthesis of Prumycin

Abstract

Benzyl 2,3-anhydro-4-azido-4-deoxy-α-L-ribopyranoside (7), an intermediate for the synthesis of Prumycin was synthesized in 72% yield in seven steps from D-arabinose. Ammonolysis of 7 followed by N-protection with the benzyloxycarbonyl group gave benzyl 4-azido-2-(benzyloxycarbonyl)amino-2,4-dideoxy-α-L-arabinopyranoside (8), which was easily converted to Prumycin.     

Spontaneous Aromatization of Diels-Alder Adducts in the Reaction of Alkatrienyl Phosphonates with Alkyl Esters of Acetylencarboxylic Acids

Abstract

The subject of this study was the Diels-Alder reaction involving dialkyl (3-methylpenta-1,2,4-trienyl)phosphonates1a-d, dialkyl(5-methyl-hexa-1,3,4-trienyl)phosphonates 2a-b, and dienophiles (esters of acetylencarboxylic acids) 3a-c, at 65–90°C, in chloroform or with no solvent. The reaction between 1a-d and 3a-b led to the benzyl phosphonates 4a-h, while with 3c it proceeds to a mixture of 5a-d (90%) and 6a-d (10%), which are dialkyl esters of the 3-carboalkoxy(or 2-carboalkoxy)-6-methyl-benzyl phosphonic acid. The intermediate Diels-Alder adducts (A) are not even spectroscopically observable, i.e. in the course of the reaction a 1,5-sigmatropic isomerization occurs, accompanied by aromatization of (A). The isomerization is spontaneous: at ambient temperature 1a-d and 3a-b react slowly and form aromatic compounds:     

Selective α-D-Galactosylation of Benzyl 4,6-O-Benzyhdene-β-D-Galacto-Pyranoside with 2,3,4,6-Tetra-O-Benzyl-α-D-Galactopyranosyl Bromide Under Catalysis by Halide Ion

Abstract

Selective glycosylation of benzyl 4,6-O-benzylidene-β-D-galacto-pyranoside (1) with 1.5 mole equivalent of 2,3,4,6-tetra-O-binzyl-α-D-galactopyranosyl bromide (2) catalyzed by halide ion gave the (1→2)-α-(5) and (l→3)-α-D-linked disaccharide (7) derivatives in 22 and 40% yields, respectively. The D-galactose unit at the reducing end of 2-O-α-D-galactopyranosyl-D-galactose [11) at equilibrium in D₂O was shown By ¹³C NMR spectroscopy to exist in the pyranose and furanose forms in the ratio of ～2:1.     

Reaction of Mercaptoacetate and Halides Containing Activated Methylenes with Thiocarbamoylimidates: A Novel Approach to the Synthesis of Aminothiazole Derivatives

The reaction of N-thiocarbamoylimidates 1 with methyl thioglycolate leads to the formation of 4-arylamino-5-methoxycarbonylthiazoles 2. The condensation of the same imidates 1 on ethyl bromoacetate, benzyl bromide and chloroacetonitrile provides the corresponding 2-arylaminothiazoles 4.