Synthesis of O-unprotected glycosyl selenoureas. A new access to bicyclic sugar isoureas

β-d-Gluco and mannopyranosyl selenoureas have been prepared by coupling of the corresponding glycosylamines with phenyl isoselenocyanate in aqueous pyridine. Alkyl and aryl isoselenocyanates, and 1,4-phenylene diisoselenocyanate have been obtained from the corresponding formamides with an excess of triphosgene, black selenium and triethylamine. Treatment of the O-unprotected β-d-glucopyranosyl selenourea with aqueous oxygen peroxide afforded a 1,2-trans-fused bicyclic isourea.     

Simple and efficient synthesis of O-unprotected glycosyl thiourea and isourea derivatives from glycosylamines

Practical, facile and high-yielding one-pot syntheses of different O-unprotected glycopyranosyl thioureas and thioureido bolaamphiphiles (two-step synthesis) and of 2-amino-4,5-dihydro-(1,2-dideoxy-β-d-glucopyranoso)[1,2-d]oxazoles (three-step synthesis) from glycopyranosylamines are reported. The method involves the preparation of O-unprotected β-d-gluco (and d-galacto)pyranosyl isothiocyanates which are in equilibrium with the corresponding 1,2-cyclic thiocarbamates, coupling with amines to afford glycosyl thioureas and treatment with yellow mercury (II) oxide to give trans-fused bicyclic isoureas. A d-gluco trehazolin analogue is prepared in this way. In situ transformation of N,N-dialkyl, N′-glucopyranosyl thioureas into the corresponding ureas is also reported.     

A facile and one-pot synthesis of N-Fmoc/Bsmoc/Boc/Z-protected ureidopeptides and peptidyl ureas employing diphenylphosphoryl azide [DPPA]

Diphenylphosphoryl azide (DPPA) mediated one-pot synthesis of N^α-Fmoc/Bsmoc/Boc/Z-protected ureidopeptides and peptidyl ureas as well as phenyl/succinimidyl (N^α-urethane protected) methyl carbamates starting from N^α-protected amino acids is reported. The formation of an azide, its rearrangement and coupling with an amino component is accomplished in a sequence of one-pot operations. The protocol has incorporated urea linkages in a sterically hindered peptide.     

Iron(III) triflate-catalyzed one-pot synthesis of acetal-type protected cyanohydrins from carbonyl compounds

A variety of cyanohydrin THP ethers were readily prepared from carbonyl compounds with trimethylsilyl cyanide and tetrahydropyran-2-yl acetate under the influence of a catalytic amount of iron(III) triflate in a convenient one-pot procedure. This method was also effective to prepare O-protected cyanohydrins by various acetal-type protective groups.     

One-pot N-dealkylation and acid-catalyzed rearrangement of morphinans into aporphines

The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na₂WO₄ as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.     

Spectrophotometric determination of aromatic primary amines and nitrite by flow injection analysis

Aromatic primary amines are determined by injection into dilute hydrochloric acid carrier which merges sequentially with 4-N-methylaminophenol and dichromate. The purple-red color formed by oxidative coupling of amines with 4-N-methylaminophenol is measured at 530 nm. In contrast to the manual procedure, the flow-injection procedure avoided errors arising from the instability of the coupling intermediate, oxidation of the amine, and too great an excess of the oxidant. The method improves the selectivity for certain amines in the presence of those which are sterically hindered or have an electron-deficient aromatic nucleus. Nitrite is determined by diazotization of sulfanilamide and quantifying the residual sulfanilamide by oxidative coupling. The sample thourghout for the assay of amines (0.05–20 μg ml^?1 NH₂-N) and nitrite (1–10 μg ml^?1 NO₂^--N) was 120 h^?1. A system for the consecutive determination of aromatic primary amines and nitrite is decribed.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

Stereoselective synthesis of 3-amino-4,5-dihydroxyaldehydes—a novel preparation of N-acetyl-l-daunosamine

A general route for the stereoselective synthesis of 3-amino-4,5-dihydroxyaldehydes, with almost any desired configuration at the three stereogenic centers, is described by applying a combination of enzymatic and chemical steps. l-Daunosamine 1, for example, the glycosidic fragment of many important anthracycline antibiotics has been prepared by this route starting from O-allyl-l-lactaldehyde (S)-6a. (R)-Hydroxynitrile lyase (HNL) catalyzed addition of HCN to (S)-6a yields the 2,3-dihydroxynitrile (2S,3S)-7a with high stereoselectivity (91% de) in 75% yield. The addition of allyl Grignard to the O-protected 2,3-dihydroxynitrile (2S,3S)-9a and subsequent hydrogenation of the imino intermediate leads to 4-amino-2,3-dihydroxy-1-heptene (4S,5S,6S)-12a, which after ozonization and deprotection gives N-acetylated l-daunosamine 14a in a total yield of 15% referring to (S)-6a. The general applicability of this chemoenzymatic multistep procedure is demonstrated in the stereoselective synthesis of the unnatural aminodeoxy sugar (2S,3S,4S)-14b, starting from isovaleraldehyde 3.     

Atom transfer radical cyclization of O-allyl-2,2-dichlorohemiacetal acetates: an expedient method to dichloro-γ-lactones

3-Alkyl-3-chloro-4-chloromethyl-γ-lactones were synthesized in acceptable yields, exploiting the CuCl-N,N,N′,N″,N″-pentamethyldiethylenetriamine catalyzed atom transfer radical cyclization (ATRC) of O-allyl-2,2-dichlorohemiacetal acetates, starting materials easily prepared from 2,2-dichloroaldehydes. The oxidation of the intermediate dichloro-2-acetoxytetrahydrofurans was completed in a two-step, one-pot procedure: hydrolysis to γ-lactol and final oxidation to lactone with Jones' reagent.     

Construction of chiral cyclopropane-fused tetrahydroquinolines: enantioselective organocatalytic Michael/alkylation domino reaction and one-pot aza-cyclization

An asymmetric two-step approach toward the synthesis of chiral cyclopropane-fused tetrahydroquinolines is described. In this synthesis, an asymmetric organocatalytic Michael/alkylation domino reaction of dialkyl bromomalonates with o-N-protected aminophenyl α,β-unsaturated aldehydes allows the process to proceed efficiently to afford the corresponding 2-formylcyclopropane products in good yields and with high enantioselectivities (up to 97% ee). In addition, a one-pot procedure for the DBU-mediated aza-cyclization of the 2-formylcyclopropane adducts was applied for the formation of chiral cyclopropane-fused tetrahydroquinolines.     

Regioselective alkylation of guanine derivatives in the synthesis of peptide nucleic acid monomers

A method for the synthesis of 6-O-benzyl- and 6-O-benzyl-2-N-benzyloxycarbonyl-protected guanine derivatives starting from 2-amino-6-chloropurin is described. A regioselective alkylation of these N(9)-protected guanine derivatives gave the corresponding α-monomers of chiral peptide nucleic acids, the L-glutamic acid derivatives. It was shown that these compound do not inhibit (in the concentrations <20 µmol L^–1) the topoisomerase I activity.     

The Heck-Matsuda arylation of 2-hetero-substituted acrylates

The Heck-Matsuda arylation of 2-aza and 2-oxo-substituted acrylates is described. Several reaction conditions were evaluated including the influence of solvents, temperature, catalysts, and stoichiometry. While the oxygenated system was successfully arylated in benzonitrile with Pd₂(dba)₃ as catalyst, the aza-acrylate furnished methoxylated products. The methoxylated products were subjected to an elimination/reduction protocol to obtain the corresponding N,O-protected phenylalanine derivatives. A one-pot procedure for the preparation of phenylalanine derivatives from 2-aza-substituted acrylates is presented.     

Towards cyclic,conformationally constrained,fluorine-containing β-amino acid derivatives from d-glucose

Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside derivatives, including the 4,6-O-benzylidene derivative and their 3-C-(N-protected aminomethyl) reduction products, as well as the phenyl 3-C-cyano-3-ethoxycarbonyl-1-thio-α-d-(and β-d-)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6-O-benzylidene-3-C-cyano-3-deoxy-3-ethoxycarbonyl-β-d-glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α-d-manno-configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6-O-benzylidene-3-C-(N-protected aminomethyl)-β-d-glucopyranoside, which led to the 2-O-methyl-α-d-mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.     

Synthesis and Reactions of 2,3,4,6-Tetra-O-Acetyl-1-S-(N-Acylaminoacyl)-1-Thio-β-D-Glucopyranoses

Abstract

Fully acetylated 1-thio-β-D-glucopyranosyl esters of N-protected amino acids (4–13) were prepared in high yields by condensation of 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (1) with a pentachlorophenyl esters of N-protected amino acids (2) in the presence of imidazole, or bN-protected amino acids (3) in the presence of DCC + imidazole. High tendency of the S-acyl aglycon group in 4–13 to undergo S → O and S → N migrations was demonstrated in reactions with several alcohols and amines.     

Chiron based synthesis of isocoumarins: reactivity of α-substituted carboxylic acids

The asymmetric synthesis of a novel (S)-isocoumarin has been attempted in a single step by the coupling of homophthalic acid with (S)-N-protected amino acids and α-chloroacids at high temperature by exploiting a chiral pool methodology. The coupling of homophthalic acid with N-protected (S)-amino acids gave exclusion of the carboxyl/alkyl group. However, coupling of homophthalic acid with α-chloroacids afforded asymmetric isocoumarins in high yield.     

A new convenient method for the synthesis of cardiolipin

A novel dichlorophosphate coupling method is developed for the synthesis of the title compound. O-Chlorophenyl dichlorophosphate can be used as a mild phosphorylating reagent to effectively couple with optically active 1,2-O-diacyl-sn-glycerol and 2-O-protected glycerol to assemble cardiolipin bearing different fatty acid chains.     

The Preparation of Acylselenourea and Selenocarbamate Using Isoselenocyanate

Acyl isoselenocyanates were prepared by a reaction of acyl chloride with KSeCN. The acyl isoselenocyanates formed in situ were ready for further reaction without concentration. N-Acyl selenoureas were obtained by a reaction of acyl isoselenocyanates with amines. The reaction of acyl isoselenocyanates with nucleophiles gave the corresponding selenocarbamate. All the compounds were well characterized by using spectral data, such as ¹³C and ⁷⁷Se NMR and X-ray diffraction.     

Simple approach to 1-O-protected (R)- and (S)-glycerols from l- and d-arabinose for glycerol nucleic acids (GNA) monomers research

5-O-Protected (-Tr, -Sitert-BuPh₂) d- and l-arabinofuranoses easily available in multigram quantities were converted to (S)- and (R)-1-O-protected glycerols, respectively, via oxidation (NaIO₄) and reduction (NaBH₄). Sources of chirality in the targets are the C4 atoms in the substrates. This stereospecific procedure permits a very simple access to both enantiomeric 1-O-protected glycerols for GNA monomers work.     

A novel solid-phase synthesis of di- and trisubstituted N-acyl ureas

A novel, mild method for the synthesis of di- and trisubstituted N-acyl ureas on solid support is described. Addition of carboxylic acids to a resin-bound carbimidoyl chloride gave, initially, an O-acyl isourea which subsequently rearranged to the corresponding N-acyl urea. Trisubstituted N-acyl ureas were assembled on a Wang resin from a wide range of Fmoc amino acids, secondary amines and carboxylic acids. Acid mediated cleavage yielded the products in good yields and excellent purities. In addition, the regioselective synthesis of disubstituted N-acyl ureas is demonstrated with four examples.     

Alkylation and aldol reactions of acyl derivatives of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates α-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH₄ to give enantiopure α-alkoxy-, α-substituted-β-alkoxy- and α,β-dialkoxyaldehydes in good yield.