Anion exchange separation of tin,antimony and tellurium

Tracer quantities of tin(IV), antimony(V) and tellurium(IV) are separated on Dowex-1 anion exchange resin in 0.1M oxalic acid. followed by 1M sulfuric acid.     

Non-hydrolytic chemoselective cleavage of Ugi tertiary amides: A mild access to N-substituted α-amino acid amides

N-Substituted α-amino acid amides can be easily obtained in two steps using the four-component Ugi reaction followed by chemoselective cleavage of the resulting tertiary amide. The use of the sacrificial acid, 2-hydroxymethylbenzoic acid is associated to shorter reaction times, higher yields, and safer and greener reaction conditions compared to strategies based on trifluoroacetic acid, a toxic and environmental hazardous reagent. The optimized procedure was easily scaled up to gram amounts.     

Synthesis of (S)-2-Boc-Amino-8-(R)-(tert-butyldimethylsilanyloxy) decanoic acid, a Precursor to the Unusual Amino Acid Residue of the Anticancer Agent Microsporin B

(S)-2-Boc-Amino-8-(R)-(tert-butyldimethylsilanyloxy)decanoic acid, the Boc-protected precursor of an unusual amino acid residue for the synthesis of microsporin B, was synthesized. The key steps include a Suzuki coupling followed by asymmetric homogeneous hydrogenation.     

A synthesis of levetiracetam based on (S)-N-phenylpantolactam as a chiral auxiliary

The synthesis of levetiracetam and its enantiomer by deracemization of (±)-2-bromobutyric acid using either (S)- or (R)-N-phenylpantolactam as chiral auxiliaries, followed by S_N2 substitution of the bromine atom by a 2-oxopyrrolidin-1-yl group and amidation of the carboxylic acid, is described.     

Total synthesis of janadolide

The first total synthesis of janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, is described. The synthesis of an unsaturated hydroxycarboxylic acid was effected via the lithiation of vinyl iodide followed by addition to a Weinreb amide with a tert-butyl group and stereoselective 1,2-reduction. The cyclic structure was constructed by macrolactamization at the amide bond between the proline moiety and fatty acid moiety.     

Carbon-carbon bond formation via a tandem cationic 2-aza-Cope rearrangement-Lewis acid promoted Petasis reaction

Potassium alkynyltrifluoroborates and potassium (2-phenyl)vinyltrifluoroborates react with N-3-butenyl-(2,2-dichloro-1-propylidene)amine in the presence of BF₃·Et₂O as a Lewis acid to synthesize rearranged Mannich products. The reaction starts with a cationic 2-aza-Cope rearrangement of the imine, followed by the Lewis acid promoted borono-Mannich-type reaction on the rearranged imine to result in a new class of functionalized N-homoallylamines.     

Synthesis and application in SPPS of a stable amino acid isostere of palmitoyl cysteine

(S)-2-Amino-4-(2-pentadecyl-1,3-dioxolan-2-yl)-butanoic acid, 11, Pdiob, a synthetic analogue C-isostere of palmitoylated cysteine, has been prepared starting from tetrabenzyl glutamic acid. The less hindered benzyl carboxylate ester was transformed into the corresponding β-ketophosphonate and subjected to a Horner-Wadsworth-Emmons reaction followed by hydrogenation/hydrogenolysis. This product was used for the preparation on solid phase and under microwave dielectric heating of a highly lipidated peptide that can be considered as an acid stable analogue of the C-terminus of the H-Ras heptapeptides 180-186.     

Synthesis of new 2,5-diamino-1,3-thiazole and 2-thiohydantoin derivatives by condensation of N-(2-Aryl-1-chloro-2-oxoethyl) carboxamides with thioureas

N-(2-Aryl-1-chloro-2-oxoethyl) carboxamides react under mild conditions with thiourea, N-alkyl-and N-arylthioureas, and various N,N′-disubstituted thioureas, following the Hantzsch reaction scheme. The reactions are selective, and the resulting 2,5-diamino-1,3-thiazole derivatives undergo recyclization acid followed by hydrolysis to give substituted 2-thiohydantoins on heating with hydrochloric acid in ethanol.     

Synthesis of amino acid conjugates of glycyrrhizic acid using <Emphasis Type="Italic">N</Emphasis>-hydroxyphthalimide and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>'-dicyclohexylcarbodiimide

Synthesis of amino acid conjugates of glycyrrhizic acid with the use of N-hydroxyphthalimide, N,N'-dicyclohexylcarbodiimide, and tert-butyl esters of L-amino acids (valine, isoleucine, phenylalanine, and methionine) was performed followed by deprotection with trifluoroacetic acid. The target amino acid conjugates were isolated by column chromatography on silica gel in 40–45% yield. The structure of the prepared compounds was confirmed by IR and ¹³C NMR spectroscopy.     

Production of enantiopure β-amino-γ-hydroxyesters from benzoic acid by a selective formal aminohydroxylation

The enantioselective preparation of three protected β-amino-γ-hydroxyesters from benzoic acid is described. The employed synthetic methodology involves the ipso, ortho cis-dihydroxylation of benzoic acid by the mutant strain Ralstonia eutropha B9, followed by a selective halonium induced beta lactamization. Modification of this novel β-lactam structure by the appropriate sequence of reactions allows for the selective preparation of the aforementioned β-amino-γ-hydroxyesters in a diastereodivergent manner. The overall transformation results in a selective formal aminohydroxylation of the diene moiety of the initial cis-cyclohexadienediol. The synthesized products are important building blocks and will allow for the selective preparation of aminoacids, inosamines and alkaloids from benzoic acid.     

Alkynes to (E)-enolates using tandem catalysis: stereoselective anti-aldol and syn-[3,3]-rearrangement reactions

A new tandem catalysis strategy that transforms alkyne derivatives to (E)-enol-equivalents followed by stereoselective anti-selective aldol coupling or syn-selective [3,3]-rearrangement transformations is reported. The mechanism is thought to proceed through an interchanging series of Lewis acid and Brønsted acid catalyzed reactions via the intermediacy of a ketiminum ion species.     

Dilactams. Synthesis of nonsymmetrical dibenzodiazocinediones

We report the first examples of nonsymmetrical dibenzodiazocinediones, mono-, di-, tri- and tetra-substituted in the aromatic rings including a benzo pyridino diazocine, by a new short method without the requirement of protection. The procedure involves conversion of an anthranilic acid to its sulfinamide lactone followed by direct heating with a different N-alkylanthranilic acid.     

An easy and stereoselective synthesis of N-Boc-dolaproine via the Baylis-Hillman reaction

In this communication we report a stereoselective total synthesis of N-Boc-dolaproine (Dap), an amino acid residue of the antineoplastic pentapeptide Dolastatin 10. Our strategy is based on a Baylis-Hillman reaction between N-Boc-prolinal and methyl acrylate, followed by a diastereoselective double bond hydrogenation and hydrolysis of the ester function.     

Enantioselective synthesis of natural biologically active ivaide A: 1,3-di-(R)-β-hydroxy-glyceride glycerol

The natural 1,3-di-β-hydroxy-glyceride glycerol ivaide A 1 from Ajuga iva has been synthesised by diacylation of dihydroxyacetone with 3-hydroxyhexadecanoic acid, followed by reduction to the corresponding glycerol derivative. The enantiomerically pure (R)-β-hydroxyhexadecanoic ester intermediate 6 was obtained by a coupling reaction of an ethylacetoacetate dianion and the corresponding bromoalkyl, followed by the known reduction of the resulting β-ketoester 5 by fermenting baker's yeast.     

The determination of zirconium in its binary alloys with niobium and tantalum

A procedure is presented for the determination of zirconium in the presence of niobium or tantalum. The bulk of the niobium or tantalum is first removed by extracting with hexone from a 10M hyclrofluoric acid, 6M sulphuric acid solution of the sample. The zirconium is then. separated from any unextractcd earth, acid element by precipitation with ammonium hydroxide followed by the addition of hydrogen peroxide. Under these conditions, both the niobium and tantalum form soluble peroxy complexes whereas the zirconium is completely precipitated from solution. After the separation of the precipitate by filtration, it is re-dissolved in hydrochloric acid and the zirconium concentration is finally determined by titration with ethylenediaminetetraacetic acid.     

A study of oxidation of benzidine, o,o′-tolidine,and o,o′-dianisidine

The oxidation of benzidine, o,o′-tolidine, and o,o′-dianisidine by the acetate complex of trivalent cobalt was studied chiefly in glacial acetic acid medium, considering the possible formation of semiquinone and quinonediimine compounds. The effect of uv light on the solutions of these compounds in glacial acetic acid and in benzene was followed spectrophotometrically and chromatographically and compared with the effect of Co(III) acetate. Certain possibilities explaining the course of the studied reactions are discussed.     

Isolation of 3,4-dihydroxyphenylacetic acid produced from p-hydroxyphenylacetic acid by immobilized plant cells of Mucuna pruriens and its identification by liquid chromatography/mass spectrometry

A cell suspension culture originating from a Mucuna pruriens (L.) DC f. utilis (Wall ex Wight) Back cultivar was immobilized in calcium alginate. Biotransformation of p- hydroxyphenylacetic acid to 3,4-dihydroxyphenylacetic acid was done in a bubble-jar containing a suitable incubation medium. To obtain a sample suitable for combined liquid chromatography/mass spectrometry (l.c./m.s.), electrolytes, proteins and carbohydrates were removed from the medium by chromatography on Sephadex G-10 and Affigel-601 columns. Product formation and isolation were followed by high-performance liquid chromatography with electrochemical and u.v. detection, and by continuous u.v. detection. The identity of 3,4-dihydroxyphenylacetic acid was confirmed by l.c./m.s., which also detected an impurity or by-product not observed by electrochemical or u.v. detection.     

The mechanism of the sonochemical degradation of benzoic acid in aqueous solutions

The sonolytic degradation of benzoic acid in aqueous solution was investigated at an ultrasonic frequency of 355 kHz. The degradation rate was found to be dependent upon the solution pH and the surface activity of the solute. The degradation rate was favoured at a solution pH lower than the pK _a of benzoic acid. At pH < pK _a, HPLC, GC and ESMS analysis showed that benzoic acid could be degraded both inside the bubble by pyrolysis and at the bubble/solution interface by the reaction with OH radicals. At higher pH (> pK _a) benzoic acid could only react with OH radicals in the bulk solution. During the sonolytic degradation of benzoic acid, mono-hydroxy substituted intermediates were observed as initial products. Further OH radical attack on the mono-hydroxy intermediates led to the formation of di-hydroxy derivatives. Continuous hydroxylation of the intermediates led to ring opening followed by complete mineralization. Mineralization of benzoic acid occurred at a rate of < 40μM/h.     

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an ¹⁸O labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products.     

Proline derivatives incorporating hydrophobic long-chain derived from natural and synthetic fatty acids

The α-hydrophobic long chain-α-amino esters are prepared by α-hydroxylation of a series of fatty acid esters [derived from oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA) and docosahexaenoic acid (DHA)] followed by Mitsunobu reaction and hydrazinolysis of the phthalimide. These amino esters are mixed with aldehydes and electrophilic alkenes to give very good chemical yields and diastereoselectivities of prolinate derivatives incorporating a hydrophobic long chain at the α-position. This multicomponent 1,3-dipolar cycloaddition (1,3-DC) takes place at room temperature. The synthesis of the homologue hydrophobic chain of OA is performed by its oxidation to aldehyde/racemic N-tert-butylsulfinyl imine/Neff reaction. Final 1,3-DC with benzaldehyde and N-methylmaleimide affords homologue prolinate derivative in good yield.