Enantiopure Trioxadecalin Derived Liquid Crystals: Influence of the Nature of the Phenyl Substituent on the Mesogenic Properties

Reaction of pseudo‐glucal 1 with Grignard reagents derived from 1‐bromo‐4‐(trimethylsilyloxy)benzene, 1‐bromo‐4‐methoxybenzene, 1‐bromo‐4‐methoxymethoxybenzene, 1‐bromo‐4‐dimethylaminobenzene, in the presence of a catalytic amount of NiCl₂(dppe), gives the corresponding unsaturated β‐C‐aryl glycosides 2. Desilylation and hydrogenation of 2 leads to β‐C‐aryl glycosides 4, which can be used as chiral precursor compounds in the synthesis of chiral liquid crystals. Combination of 4 with arylaldehydes leads to compounds 5–7, whereas reaction with p‐alkoxysubstituted phenylboronic acids gives the trioxaboradecalins 8–11. The mesogenic properties of these compounds are strongly influenced by the nature of the substituent on the phenyl ring in the molecule.     

Preparation and characterization of phenyl carbamate derivative β-cyclodextrin bonded phase for chiral HPLC

A partially substituted β-cyclodextrin chiral stationary phase was prepared by the reaction of phenyl isocyanate. The enantiomers of a series of O,O-diethyl(p-methylbenzenesulfonamido)-aryl(or alkyl)-methylphosphonates were studied on the prepared phenyl carbamate derivative β-cyclodextrin bonded phase and a commercial (S)-(+)-1–(1-naphthyl) ethylcarbamate derivative β-cyclodextrin bonded phase on normal phase chromatographic condition. Results show that the prepared phenyl carbamate derivative β-cyclodextrin bonded phase has better enantiomeric selectivity to the series of compounds. A chiral recognition mechanism was suggested for the separation of these novel organic phosphorus enantiomers.     

Thiosugars Iii. Stereoselective Approach to β-(1→2)-2,3-Dideoxy-2-C-Acetamidomethyl-2-S-Thiodisaccharides From Levoglucosenone

ABSTRACT

β-(1→2)-2,3-Dideoxy-2-C-acetamidomethyl-2-S-thiodisaccharides were synthesized in four steps by a stereoselective base catalyzed Michael addition reaction of 1-thiosugars to α-nitroalkene 4a, a new chiral synthon from levoglucosenone. It was followed by the reduction of the nitro group with a sodium borohydride/cobalt chloride complex and the hydrolytic opening of the 1,6-anhydro ring.     

Chemical Synthesis of N-Aryl Glycosides

Along with the O- and C-aryl glycosides, N-aryl glycosides represent an important class of carbohydrate and heterocyclic aryl conjugates that possess diverse applications and implications of biological interest. However, most of the synthetic efforts have been directed toward the preparation of O- and C-aryl glycosides. This review focuses on the various strategies that have been employed to synthesize N-aryl glycosides, most of which developed in the past 20 years. Besides having their unique applications, these N-aryl glycosides can also be treated as the analogs of O- and C-aryl glycosides. Wide ranges of reaction conditions are discussed for the optimum conditions.     

Mono-Glycosylated 3-N-Alkylcatechols: Direct Synthesis from Glycosylacetates, 1H Nmr Analysis and Conformational Studies

ABSTRACT

The direct coupling of 3-n-alkyl catechols to the acetate or trichloroacetimidate derivatives of β-D- or α-D-glycosides (glucose, galactose, xylose, mannose and maltose) catalyzed by BF₃Ot₂ has been studied. β-Glycosides with an equatorial acetate group at position 2 formed exclusively β adducts with yields of 60–80%. α-Glycosides with an equatorial acetate group at position 2 formed β adducts, while β-glycosides with an axial acetate group formed α adducts when activated as trichloroacetimidates, with yields of 70–85%. This was applied to the coupling of 3-n-alkylcatechols of increasing chain length (up to C15) to sugar derivatives. The coupling position of glycosides on the catechol was determined either by differential NOE experiments and by the regioselective synthesis of 1-(O-β-D-glucopyranosyl)-3-pentadecylcatechol, a water soluble analogue of the poison ivy skin allergen. ¹H NMR of acetylated and deprotected compounds were investigated and the conformational preferences of the C₆ side chain determined using molecular modeling.     

Reaction of 2,3-O-Isopropylidene-D-Glyceraldehyde and Some Dialkyl and Diarylthiomethyl Sulfoxides: Stereochemical Aspects

Abstract

The reaction of 2,3-O-isopropylidene-D-glyceraldehyde with different dialkyl and diarylthiomethyl sulfoxides occurs with a high selectivity and produces the corresponding 1-alkyl(or l-aryl)-sulfynil-l-alkyl(or 1-aryl) thio-3,4-O-isopropylidene-D-tetroses as pure diastereoisomers. We have determined the absolute configuration of the three chiral centers formed in these reactions.     

Two new flavonol glycosides from Dimocarpus longan leaves

From the extracts of Dimocarpus longan Lour leaves, 2 unusual flavonol glycosides, quercetin 3-O-(3″-O-2?-methyl-2?-hydroxylethyl)-β-d-xyloside (1) and quercetin 3-O-(3″-O-2?-methyl-2?-hydroxylethyl)-α-l-rhamnopyranoside (2), as well as 10 known compounds including 2 flavonol glycosides, afzelin (3) and kaempferol-3-O-α-l-rhamnopyranoside (4), 2 flavans, ( ? )-epicatechin (5) and proanthocyanidin A-2 (6), 3 triterpenoids, friedelin (7), epifriedelanol (8) and β-amyrin (9), a peptide, N-benzoylphenylalanyl-N-benzoylphenylalaninate (10), and 2 sterols, β-sitosterol (11) and daucosterol (12) were isolated and identified by using combination of mass spectrometry and various 1D and 2D NMR techniques. This is the first report of flavonoid glycosides possessing a 2-methyl-2-hydroxylethoxyl group in sugar moiety from D. longan.     

Synthesis of new 6-Aroylpyrido[2,3-d]pyrimidines

The synthesis of 6-dimethylaminomethylenaminopyrimidin-4(3H)-ones 2 and its reaction with β-dimethyl-aminopropiophenone hydrochloride 3 is discussed in this work. The reaction of 6-aminopyrimidin-4(3H)-ones 1 with an excess of dimethylformamide dimethyl acetal gives rise to the formation of 6-dimethylaminomethyleneaminopyrimidines 2. The heating of equimolecular quantities of 2 and 3 in dimethylformamide leads to the 6-aroylpyrido[2,3-d]pyrimidines derivatives 4. The structures of compounds 2 and 4 were determined on the basis of nmr measurements.     

Two new glycosides isolated from Sapindus mukorossi fruits: effects on cell apoptosis and caspase-3 activation in human lung carcinoma cells

Two new glycosides (1, 2) and two saponins (3, 4) were isolated from the fruits of Sapindus mukorossi Gaertn. The two glycosides were designated as sapindoside G (1) and 4′′,4′′′′′-O-diacetylmukurozioside IIa (2). All four compounds exhibited inhibitory effects against A549 human lung adenocarcinoma cells with inhibition rates up to 69.2–83.3% at a concentration of 100 μg/mL. Flow cytometric analysis revealed that compounds 1–4 could suppress A549 cell growth by promoting cell apoptosis, which was related to the activation of caspase-3.     

Synthesis of 1,3-Bis[(3-aryl)-S-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes

1,3-bis[(3-aryl)-s-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes 2 were synthesized in high yields by the reaction of 3-aryl 4-amino-5-mercapto-1,2,4-triazole 1 with m-phthalic acid.     

HSAB-driven regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-substituted glycals with sulfur and oxygen nucleophiles: direct versus allylic substitution

A remarkable regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-acteoxymethyl glycals with thiophenols and phenols has been observed. The reaction with thiophenols led to preferential formation of a new class of compounds viz. 2-C-arylthiomethyl glycals via direct attack at the C-2 side chain primary carbon bearing the leaving group. In contrast, phenols were reported to afford predominantly 2-C-methylene-O-aryl glycosides via allylic attack at the anomeric carbon. The observed results correlate well with the HSAB principle proposed earlier for similar type of reactions with simple glycals. In addition, formation of an unusual bis-thioarylated product in presence of an excess of thiophenol is also reported.     

Haloacetylated enol ethers. 13. Synthesis of N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-1-buten-1-yl]-o-phenylenediamines and 2-trichloromethyl-4-aryl-3H-1,5-benzodiazepines

The synthesis and isolation of the intermediates N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-1-buten-1-yl]-o-phenylenediamines 2a-f and the corresponding 2-trichloromethyl-4-aryl-3H-1,5-benzodiazepines 3c-g or benzimidazoles 4a-b derivatives obtained from the intramolecular cyclization of 2a-f or from direct cyclo-condensation reaction of β-alkoxyvinyl trichloromethyl ketones 1a-g with o-phenylenediamine, is reported. Depending of the structure of the β-alkoxyvinyl trichloromethyl ketones or the N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-buten-1-yl]-o-phenylenediamines and the reactions conditions, benzimidazoles or 3H-1,5-benzodiazepines were obtained.     

Synthesis of C-Glycosyl Isoxazoles and Branched-Chain Enuloses From 2,3-O-Isopropylidene-D-Glyceraldehyde

Abstract

The synthesis of 5-glycosyl isoxazoles with 3-alkyl-, 3-aryl, 3,4-dialkyl, 3-aryl-4-alkyl or 3-alkyl-4-bromo substituents is reported. Deoxyenuloses were obtained from reaction of 2,3-O-isopropylidene-D-glyceraldehyde and several phosphorus ylides, which contain a carbonyl group, by a Wittig reaction. C-glycosyl α,β-unsaturated ketones were obtained, with the polyhydroxylate chain lengthened by two or three carbon atoms. In the second phase the ketones were transformed into the corresponding C-glycosyl α,β-unsaturated ketoximes, leading to the C-glycosyl isoxazoles, which were converted into the title compounds via removal of the isopropylidene group of suitably protected carbohydrates. The solubility of the synthetized C-glycosyl isoxazoles were modified by free hydroxyl groups in such a way that their behaviour against certain viruses and their potential antiviral activity could be studied.     

Alkylidenation of Sugar Lactones and Further Transformation to C-Glycosides

ABSTRACT

The Witting reaction of (carbethoxymethylene)triphenylphosphorane with perbenzylated sugar δ-lactones and their 2-acetamido-2-deoxy derivatives is described. It is shown that this olefination occurred readily with the galacto and gluco derivatives, leading stereoselectively to Z-C-glycosylidenes in good yields. However, the same reaction with the perbenzylated 2-deoxy-D-arabino-hexono-1,5-lactone and the mannonolactones worked poorly. Reduction over Pd/C followed by acetylation of the obtained C-glycosylidenes led stereoselectively to peracetylated β-C-glycosides and amino β-C-glycosides. The olefin function could also be reduced selectively by Raney nickel or NiCl₂/NaBH₄, affording the perbenzylated C-glycosides and amino β-C-glycosides. Other transformation of the enol ether function is also reported.     

Synthesis and Antimicrobial Evaluation of Novel N-Substituted β-Hydroxy Benzimidazole Sulfone Fluoroquinolones by Selective Oxidation Using Ticl4-H2O2

Abstract

The synthesis of N-substituted β-hydroxy benzimidazole sulfones containing 8-methoxy fluoroquinolone has been described and they were evaluated for antimicrobial activities. The compounds of N-substituted β-hydroxy benzimidazole sulfides (4a–e) and N-substituted β-hydroxy benzimidazole sulfones (5a–e) at C-7 of fluoroquinoline exhibited superior activity in vitro. 8-Methoxy fluoroquinolone carboxylic acid (1), reaction with piperizine in acetonitrile in presence of triethylamine under reflux gives 7-piperazinyl-8-methoxyfluoroquinolone (2). The latter is reacted with epichlorohydrine in presence of NaOH in acetone yielded N-substituted epoxide (3), which on treatment with 5-substituted-2-mercaptobenzimidazoles gives N-substituted β-hydroxy benzimidazole sulfides (4). Further, 4 on treatment with TiCl₄-H₂O₂ and in DCM yielded the corresponding N-substituted β-hydroxy benzimidazole sulfone (5).     

New cytotoxic lignan glycosides from Phyllanthus glaucus

During the process of exploring bioactive lead compounds from Phyllanthus species, two new glycosides including an arylnaphthalene lignan, diphyllin 4-O-α-l-arabinopyranosyl-(1 → 3)-α-l-arabinopyranoside (1), and a phenolic compound, 3,4,5-trimethoxybenzyl alcohol 7-O-α-l-arabinofuranosyl-(1 → 6)-β-d-glucopyranoside (2), were isolated from the methanol extract of the whole plants of Phyllanthus glaucus Wall. ex Müll. Arg. In addition, 31 known compounds, including 19 lignan derivatives (3–21), four phenylpropanoids (22–25), seven simple phenolics (26–32) and one monoterpenoid (33) were obtained. Their structures were determined on the basis of the HR-ESI-MS, 1D and 2D NMR spectroscopic analysis, and pre-column derivative/chiral HPLC analysis in case of 1 for the absolute configurations. All these compounds were obtained from P. glaucus for the first time. Moreover, the known lignan glycoside, phyllanthusmin C (5) showed in vitro cytotoxicities against HL-60, MCF-7 and SW480 cells with IC₅₀ values of 9.2 ± 0.2, 19.2 ± 1.7 and 20.5 ± 0.9, respectively.     

Antiangiogenic phenylpropanoid glycosides from Gynura cusimbua

A new phenylpropanoid glycoside, named α-L-rhamnopyranosyl-(1?2)-β-D-[4″-(8E)-7-(3,4-dihydroxyphenyl)-8-propenoate, 1″-O-(7S)-7-(3,4-dihydroxyphenyl)-7-methoxy-ethyl]-glucopyranoside (1), together with nine known compounds (2–10) were isolated from the active fraction (n-Butanol fraction) of Gynura cusimbua for the first time. The known compounds (2–10) were identified as phenylpropanoid glycosides on the basis of extensive spectral data and references. The antiangiogenic activities of compounds (1–10) were evaluated by MTT assay on HUVECs and wild-type zebrafish in vivo model assay. As a result, compounds 1, 6, 7, 8 and 10 exhibited certain antiangiogenic activities.     

Mechanism of cerium (IV) oxidation of glucose and cellulose

Cerium (IV) oxidations of model compounds for the hydroxylic functional groups of cellulose were conducted in 1.0M perchloric acid. Glucose, the model selected for the reducing end group, was oxidized 360 times faster than Schardinger β-dextrin, the model for anhydro-D -glucose repeating units. In the presence of a fourfold excess of glucose, stoichiometry indicated specific conversion to arabinose; the competitive oxidation of arabinose produced is insignificant. Specific C₁–C₂ bond cleavage was also indicated for 2-O-methyl-D -glucose, galactose, 2-O-methyl-D -galactose, and cellobiose. Anhydro-D -glucose units were oxidized predominantly by C₂–C₃ bond cleavage as shown by the identification of erythrose and glyoxal in hydrolyzates of cerium (IV) oxidized Schardinger β-dextrin and cellulose. Kinetic studies showed that chelate complexes were involved in oxidations of glucose, methyl β-D -glucopyranoside, 1,5-anhydro-D -glucitol, and Sahardinger β-dextrin. The oxidations of glucose derivatives which differed with respect to substituents on C₁ and C₂ demonstrated the importance of the hemiacetal group and the presence of oxygen on C₂. For example, the relative rates of oxidation at 15°C for methyl β-D -glucopyranoside, 1,5-anhydro-D -glucitol, 2-deoxy-D -glucose, glucose, and 2-O-methyl-D -glucose are 1:1:12:360:1860, respectively. The mechanism of glucose oxidation is thought to involve formation of a chelate complex, disproportionation of the complex to form a free radical at either C₁ or C₂ and further rapid oxidation to 4-O-formyl-D -arabinose which is hydrolyzed in the reaction medium. General implications of the experimental results pertaining to initiation of vinyl graft polymerization on cellulose are discussed.     

Synthesis of spiro[1,4-benzothiazine-2,2′-pyrans] starting from methyl β-D-arabino-2-hexulopyranosonate

Dedicated to Professor Klaus Burger on the occasion of his 60th birthday Methyl β-D -arabono-2-hexulopyranosonate 1 has via the novel glycosyl donor 3 been transformed into the thiophenyl glycosides 4 and 5. Catalytic hydrogenation of the nitro compound 4 in alkaline solution led to spontaneous cyclization and deprotection to form the cyclic hydroxamic acid 7. The related lactams 8 and 9 were obtained from amine 5. The spiro[1,4-benzothiazine-2,2′-pyrans] 7–9 are the first representatives of a novel class of heterocycles structurally related to bioactive natural products. As shown by the values for J_3′,4′ and J_4′,5′ the glycosides 4, 5 and 6 adopt a ⁵C₂ conformation of the pyranoid ring whereas the 1,4-benzothiazine system in 7–9 forces a conformational change into the ²C₅ conformation.     

THE SYNTHESIS OF SOME C-4 AND C-9 SUBSTITUTED DERIVATIVES OF KDN2EN METHYL ESTER

The synthesis of a number of C-4 and C-9 substituted derivatives of KDN2en methyl ester 2 is reported. 9-Deoxy-9-iodo, 9-azido-9-deoxy and 9-O-methyl derivatives of 2(compounds 5, 7and 9) were prepared from the corresponding 9-O-tosylate, methyl 2,6-anhydro-3-deoxy-9-O-p-toluenesulfonyl-D-glycero-D-galacto-non-2-enonate (3). These compounds have been fully characterised as the peracetates 6, 8 and 10. Treatment of 3 with KSAc gave the 9-thioacetyl derivative which was isolated as the peracetate 11. 4-C-Ethenyl-4-deoxy (14), 4-C-phenyl-4-deoxy (15) and 4-C-[1-(methoxycarbonyl)ethenyl]-4-deoxy (16) derivatives of 2were prepared via the palladium-catalysed coupling of the 4-epi-chloride, methyl 5,7,8,9-tetra-O-acetyl-2,6-anhydro-4-chloro-3,4-dideoxy-D-glycero-D-talo-non-2-enonate (12) with the appropriate organostannanes.