Chemistry of naphthazarin derivatives. Transetherification selectivity of naphthazarin methoxy derivatives

Transetherification of naphthazarin methoxy derivatives in basic conditions occurs only with primary monohydric alcohols. 1,3-Butanediol due to the assistance of the hydroxy group at the C¹ atom gives rise to a mixture of transetherification products at the primary and secondary hydroxy groups in a ratio 3: 1. The reaction with methyl α-D-glucopyranoside affords predominantly methyl 6-O-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-α-D-glucopyranoside, previously unknown water-soluble naphthoquinone-carbohydrate conjugate.     

Reactions of methylcopper and chiral organocuprates with 1-nitro-2-phenylethene and of lithium dimethylcuprate with methyl 3(nitrophenyl)propenoates

Organocopper compounds like methylcopper, lithium dimethylcuprate, chiral lithium methyl-(S)-2(1-dimethylaminoethyl)-phenylcuprate and lithium menthoxy(methyl)cuprate react with 1-nitro-2-phenylethene to give the conjugate addition product 1-nitro-2-phenylpropane in moderate yields. In the reaction with lithium methyl-(S)-2(1-dimethylaminoethyl)phenylcuprate 2% asymmetric induction was obtained. The reaction between lithium dimethylcuprate and methyl 3(4-nitrophenyl)propenoate gave the corresponding azoxy compound and no conjugate addition product, while methyl 3(3-nitrophenyl)propenoate gave some conjugate addition.     

Concise and highly selective asymmetric synthesis of acosamine from sorbic acid

Diastereoselective conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl sorbate and subsequent chemo- and diastereoselective ammonium-directed olefinic oxidation of the resultant conjugate addition product {tert-butyl (3S,αR)-3-[N-benzyl-N-(α-methylbenzyl)amino]hex-4-ene} have been used as the key steps in a concise and highly selective asymmetric synthesis of the 2,3,6-trideoxy-3-aminohexose l-acosamine. This sequence of two chemical operations allows rapid assembly of the molecular architecture and facilitates the de novo asymmetric synthesis of methyl N,O-diacetyl-α-l-acosaminide in only 7 steps from commercially available sorbic acid in 15% overall yield.     

Silafunctional compounds in organic synthesis. 28. Conjugate addition of a hydroxymethyl anion synthon to α,β-enones

The title reaction has been achieved by a sequence of the copper-catalyzed conjugate addition of the (allyldimethylsilyl)methyl Grignard reagent, fluorodeallylation and the H₂O₂-oxidation of the carbon-silicon bond therein.     

Direct vinylation of glucose derivatives with acetylene

Vinyl ethers, promising chiral carbohydrate synthons, have been synthesized by the addition of glucose acetals (1,2:5,6-di-O-isopropylidene-α-d-glucofuranose, methyl 4,6-O-benzylidene-α-d-glucopyranoside, 1,2-O-cyclohexylidene-α-d-glucofuranose, methyl α-d-glucopyranoside) to acetylene under atmospheric and elevated pressures in an autoclave in the presence of superbase catalytic systems (KOH-DMSO, t-BuOK-DMSO). The complete vinylation of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose and methyl α-d-glucopyranoside has been realized under elevated pressure of acetylene in the system KOH-THF as well.     

Synthesis of the repeating trisaccharide unit of the cell wall lipopolysaccharide of Escherichia coli type 8

NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-α-d-mannopyranoside with phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-d-mannopyranoside furnished the corresponding disaccharide derivative in excellent yield and α-selectivity. Zémplen deacetylation of the same followed by reaction with BSP/Tf₂O-preactivated phenyl 4,6-O-benzylidene-2,3-di-O-benzyl-1-thio-α-d-mannopyranoside generated methyl 4,6-O-benzylidene-2,3-di-O-benzyl-β-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranoside in very good yield and excellent β-selectivity. Pd/C catalyzed hydrogenation of the latter finally afforded the repeating trisaccharide of Escherichia coli 8 O-antigen as its methyl glycoside.     

Enantioseparation of Methyl 2-Hydroxypropionate with Two Peracylated β-Cyclodextrin Derivatives as CGC Chiral Stationary Phases

Two peracylated β-cyclodextrin derivatives, 2,3,6-tri-O-valeryl-β-cyclodextrin and 2,3,6-tri-O-octanoyl-β-cyclodextrin, were synthesized and used as capillary gas chromatography (CGC) chiral stationary phases. The two peracylated β-cyclodextrin derivatives showed enantioseparation abilities to some chiral compounds tested, such as enantiomers of methyl 2-chloropropionate, 5-hydroxy-4, 4-dimethyl-dihydrofuran-2-one, and methyl 2-hydroxypropionate. As CGC chiral stationary phases, the two peracylated β-cyclodextrin derivatives showed excellent enantioseparation abilities to methyl 2-hydroxypropionate (i.e., methyl lactate). On 2,3,6-tri-O-valeryl-β-cyclodextrin, the enantiomer separation factor and resolution of methyl lactate were 1.21 and 6.08, respectively, and on 2,3,6-tri-O-octanoyl-β-cyclodextrin, 1.22 and 5.49, respectively. The enantioseparation results of methyl lactate on the two peracylated β-cyclodextrin derivatives were better than on most reported β-cyclodextrin derivatives, including a commercial chiral column of permethylated β-cyclodextrin tested in this study. Results suggest that CGC methods using 2,3,6-tri-O-valeryl-β-cyclodextrin or 2,3,6-tri-O-octanoyl-β-cyclodextrin as chiral stationary phase could be used for enantioseparation and evaluating the enantiomeric optical purity of methyl lactate.     

Asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine,jaspine B (pachastrissamine) and its C(2)-epimer

The highly diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to a γ-silyloxy-α,β-unsaturated ester and in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine has been used as the key step in the asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine, jaspine B (pachastrissamine) and its C(2)-epimer.     

Fluorsilylsubstituierte N,N- und N,O-bis(trimethylsilyl)-hydroxylamine

Fluoro- und aminofluoro-silanes react with the lithium salt of N,O-bis(trimethylsilyl)hydroxylamine under LiF elimination and substitution. Alkyl- and amino-fluorosilanes give O-fluorosilyl-N,N-bis(trimethylsilyl)hydroxylamines, arylfluorosilanes give N-fluorosilyl-N,O-bis(trimethylsilyl)hydroxylamines. By the further reaction of O-difluorosilyl-N,N-bis(trimethylsilyl)hydroxylamine with the lithiated hydroxylamine, O,O′-fluoromethylsilyldi[N,N-bis(trimethylsilyl)hydroxylamine] is formed. On heating N-difluorophenylsilyl-N,O-bis(trimethylsilyl)hydroxylamine di[fluorophenylsilyl(methyl)amino]pentamethylsiloxane is formed by methyl group migration. The NMR and mass spectra of the compounds are reported.     

One-pot synthesis of N-substituted (3-oxobutanyl)carbamates from primary amines using modified zeolite Hβ at room temperature

The one-pot synthesis of N-substituted (3-oxobutanyl)carbamates via the tandem condensation of primary amines with methyl chloroformate, followed by the conjugate addition of the resulting carbamate with methyl vinyl ketone in the presence of Sn⁴⁺ modified zeolite Hβ (Hβ-SnA) at room temperature is described.     

Regio- and stereoselective syntheses of l-pentose derivatives from l-arabinose

Novel l-arabinose, l-ribose, 2-deoxy-l-ribose and 2-fluoro-2-deoxy-l-arabinose derivatives were synthesized from readily available l-arabinose. Different synthetic routes to methyl 3,5-di-O-acylated-l-arabino(ribo)furanosides as valued intermediates for the preparation of C-2 functionalized l-pentoses were investigated via regioselective transformations of 1,2-di-O-acetyl-3,5-di-O-pivaloyl-l-arabinofuranose, and selective acylation of methyl l-arabinofuranoside with 4-chlorobenzoyl or pivaloyl chloride. Short three-five-step syntheses of methyl 2-deoxy-α-l-ribofuranoside, its 3,5-di-O-acyl derivatives, valuable precursors for preparation of antiviral 2′-deoxy-l-nucleosides, were accomplished via simple and efficient reduction of methyl 2-O-mesyl-l-arabinofuranoside with L-Selectride or tandem reaction involving a complex hydride 2-deoxygenation/acylation of intermediate 2-deoxysugar. A new synthesis of 2′-deoxy-2′-fluoro-β-l-arabinofuranosyl thymine (l-FMAU) was performed using a mild fluorination of protected l-ribofuranoside and a novel sequence of conversions for the preparation of 2-deoxy-2-fluoro-l-arabinofuranoside derivatives.     

Synthesis of mono-, di- and trisulfated Lewis x trisaccharides

3′-Sulfated and 3′,6′-disulfated Lewis x trisaccharides have been prepared through selective sulfation of methyl 2-acetamido-6-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-3-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-β-D-glucopyranoside, followed by catalytic hydrogenolysis. In a similar manner, 3′,6-disulfated and 3′,6,6′-trisulfated Lewis x trisaccharides have been selectively obtained from methyl 2-acetamido-2-deoxy-4-O-β-D-galactopyranosyl-3-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-β-D-glucopyranoside.     

Reliable evaluation of molecular structure of methyl 3-O-nitro-α-d-glucopyranoside and its intermediates by means of solid-state NMR spectroscopy and DFT optimization in the absence of appropriate crystallographic data

In this paper the comparative structural analysis of a series of compounds (methyl α-d-glucopyranoside, methyl 4,6-O-ethylidene-α-d-glucopyranoside (2), methyl 2,3-di-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside and methyl 3-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside) by way of synthesis leading to methyl 3-O-nitro-α-d-glucopyranoside (5) is reported. The title compound (5) is a novel d-glucosidic mononitrate having potential biological activity against cardiovascular diseases. The structural analysis was supported by single-crystal X-ray diffraction (XRD), ¹³C CP/MAS NMR spectroscopy and DFT calculations. In the case of 2 and 5, XRD analysis could not be performed due to the fact that 2 is highly hygroscopic and 5 forms improper crystals. However, the molecular structures of 2 and 5 were obtained on the basis of experimental (existing XRD data for similar compounds) and theoretical (DFT optimization) approaches. This showed of very good agreement with the ¹³C CP/MAS NMR spectral data.     

Doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to enantiopure ε-O-protected α,β-unsaturated esters derived from d-ribose

Enantiopure ε-O-silyloxy- and ε-O-benzyloxy-α,β-unsaturated esters derived from d-ribose, each containing a cis-dioxolane unit, display excellent (⩾95:5 dr) levels of diastereofacial directing ability upon conjugate addition of achiral lithium N-benzyl-N-isopropylamide. In contrast to the corresponding enantiopure ε-O-silyloxy-α,β-unsaturated ester derived from l-tartaric acid, which contains a trans-dioxolane unit, the conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to its cis-configured counterpart result in doubly diastereoselective ‘matched’ and ‘mismatched’ reaction pairings in which the inherent reagent control serves to augment or oppose, respectively, the established substrate diastereocontrol.     

Conjugate addition of hydroxylamino derivatives to alkylidene malonates in the presence of chiral Lewis acids

The conjugate addition of O-benzylhydroxylamine and N,O-bis(trimethylsilyl)hydroxylamine to alkylidene and arylidene malonates in the presence of Lewis acids affords the corresponding β-hydroxylamino derivatives in good yields. The use of Cu(OTf)₂ in the presence of chiral bisoxazoline ligands opens the possibility of performing this reaction in a catalytic and enantioselective way.     

Convenient use of ortho-formylphenyl thioglycoside for regioselective conjugation with glycosyl acceptors towards regioselective 1,2-cis-glycosylation

A facile methodology is proposed for regioselective conjugation between glycosyl donors and acceptors towards the development of regioselective 1,2-cis-glycosylation method. ortho-Formylphenyl 1-thio-β-d-galactopyranoside was regioselectively tethered to methyl α-d-glucopyranoside under acidic condition to furnish an 4,6-O-arylidene acetal-linked conjugate. This conjugate can be readily converted to an ether-linked 4-O- or 6-O-derivative by regioselective cleavage of the acetal ring. In the glycosylation reaction, the ether-linked 4-OH conjugate was found to show excellent 1,2-cis selectivity via an intramolecular 1,9-transfer.     

The first synthesis of secondary sugar sulfonic acids by nucleophilic displacement reactions

The 4-deoxy-4-C-sulfonic acid and 6-deoxy-6-C-sulfonic acid derivatives of methyl α-d-gluco- and α-d-galactopyranosides were prepared by triflate-mediated nucleophilic displacement reactions, either with NaHSO₃ or with AcSK. The triflate esters of methyl 2,3,4-tri-O-benzyl- 1, methyl 2,3,6-tri-O-benzyl-α-d-glucopyranoside 9 and methyl 2,3,6-tri-O-benzyl-α-d-galactopyranoside 5 provided methyl 6-deoxy-6-C-sulfo-α-d-glucopyranoside 4, methyl 4-deoxy-4-C-sulfo-α-d-galactopyranoside 12 and α-d-glucopyranoside 8, respectively. The triflate derivative of methyl 2,3,4-tri-O-benzyl-α-d-galactopyranoside 13 gave methyl 3,6-anhydro-2,4-di-O-benzyl-α-d-galactopyranoside 14. Formation of the 3,6-anhydro derivative was prevented by using 3,4-O-isopropylidene acetal protection to obtain methyl 6-deoxy-6-C-sulfo-α-d-galactopyranoside 19. The aim of the research is to replace the sulfate esters by sulfonic acids in the repeating oligosaccharide units of glycosaminoglycans or in different oligosaccharide ligands.     

Conjugate addition of chiral lithium methyl[o(cyclohexyldimethylaminomethyl)phenyl]cuprate to methyl 3-phenyl-2-propenoate and 4-phenyl-3-buten-2-o

Chiral lithium methyl[o-(cyclohexyldimethylaminomethyl)phenyl]cuprate reacts with methyl 3-phenyl-2-propenoate and 4-phenyl-3-buten-2-one to give the conjugate addition products, viz. methyl 3-phenylbutanoate and 4-phenylpentan-2-one respectively. The reaction rates and chemical yields (30–60%) are lower than in corresponding reactions with lithium dimethylcuprate and lithium methyl[2-(1-dimethylaminoethyl)phenyl]cuprate respectively. Lithium halides in the reaction favour the formation of one enantiomer. The highest asymmetric induction obtained is 4.4%.     

Asymmetric total synthesis of botcinic acid and its derivatives: synthetic revision of the structure of botcinolides

The stereoselective total syntheses of botcinic acid, botcinic acid methyl ester, 3-O-acetylbotcinic acid methyl ester, botcineric acid, and botcinin E were achieved. The structures of these compounds have been unequivocally determined through their total synthesis, and they are identified with the revised structures of botcinolide, 4-O-methylbotcinolide, 3-O-acetyl-5-O-methylbotcinolide, homobotcinolide, and 2-epibotcinolide, respectively.     

α-Oxoketene dithioacetal mediated aromatic annulation: highly efficient and concise synthetic routes to potentially carcinogenic polycyclic aromatic hydrocarbons

Highly efficient regiospecific routes to potentially carcinogenic polycyclic aromatic hydrocarbons such as substituted benzo[c]phenanthrenes, benzo[c]fluorenes, 16,17-dihydro-11-methyl-15[H]cyclopenta[a]phenanthrene, 5-methyl-7,8,9,10-tetrahydrochrysene and 1,4-dimethylphenanthrene have been developed. The overall strategy involves our aromatic annulation protocol through base induced conjugate addition-elimination on the cyclic and acyclic α-oxoketene dithioacetals with the appropriate arylacetonitriles followed by acid induced cyclodehydration of the resulting conjugate adducts. Subsequent reductive dethiomethylation (Raney Ni) and dehydrogenation (DDQ) of the cyclized products affords the methyl substituted PAHs in high yields.