Synthesis of Novel 2‐Vinylcyclopropane Phosphonic Acids

2‐Vinylcyclopropane‐1‐phosphonic acid diesters 1a–d were synthesized by the reaction of trans‐1,4‐dibromo‐2‐butene with α‐substituted phosphonic acid diesters. Esterification of 1‐ethoxycarbonyl‐2‐vinylcyclopropane‐1‐carboxylic acid with dimethyl 2‐hydroxyethyl‐phosphonate gave the 2‐vinylcyclopropane phosphonic acid dimethylester 1e. The silylation of phosphonic acid diesters 1a–e by halotrimethylsilanes followed by solvolysis with methanol or water resulted in the formation of phosphonic acids 2a–e. In the case of steric hinderance of the phosphoryl group, monoesters 3c,d were also formed. Furthermore, ethyl carboxylate 1b could be chemoselectively cleaved by aqueous potassium hydroxide to carboxylic acid 4.     

Preparation of Bromoiodopropenoic Acids by Stereospecific Nucleophilic Substitution at Vinylic Carbon

The bromoiodopropenoic acids (E)‐2‐bromo‐3‐iodopropenoic acid 5 and (Z)‐2‐bromo‐3‐iodopropenoic acid 6 were prepared by stereospecific nucleophilic substitution of the corresponding vinylic bromides. The structure of the (Z)‐isomer was confirmed by X‐ray crystallography.     

Poly(3,5‐dichloroaniline) Doped with Different Sulfonic Acids

Poly(3,5‐dichloroaniline) was prepared by chemical oxidation in the presence of various sulfonic acids as doping agent, using potassium permanganate as oxidant. 1‐Naphtalene sulfonic acid, 2‐naphatalene sulphonic acid, 1,5‐naphtalene disulfonic acid, and p‐toluenesulfonic acid were the acids of choice. Infrared and UV‐Vis spectroscopy, utilized to characterize the polymers, revealed that the compounds exist in the emeraldine (conductive) oxidation state. The level of doping, conductivity, and morphology were determined as well. The presence of a sulfonic acid produces a morphological change, from granular to microtubule structures, which is responsible for the strong increase in the conductivity of the polymer.     

A Practical One‐Pot Synthesis of New S‐Glycosyl Amino Acid Building Blocks for Combinatorial Neoglycopeptide Synthesis

S‐Glycosyl L‐aspartic acid building blocks were synthesized starting from 1‐thiosugars by reaction with 5‐aminopentanol and suitably protected L‐aspartic acid pentafluorophenyl ester in a one‐pot procedure under Mitsunobu conditions using 1,1′‐azodicarbonyl dipiperidine and trimethyl phosphine. The method allowed for the preparation of S‐glycosyl amino acid building blocks in one step without protection of the amino function for the Mitsunobu condensation. Alternatively, the title compounds were prepared by a stepwise approach via 5‐aminopentyl 1‐thioglycosides.     

Synthesis of 3‐Methoxyoxetane δ‐Amino Acids with D‐lyxo,D‐ribo,and D‐arabino Configurations

Starting from 1,2‐isopropylidene‐d‐xylose (1), 3‐methoxyoxetane δ‐amino acids with d‐lyxo, d‐ribo, and d‐arabino configurations were synthesized. The early introduction of an azide function at C‐5 of 1 shortened the synthetic pathway. Ring contraction of the intermediate d‐xylono‐1,4‐lactone 6 via triflation and treatment with base led to the corresponding 3‐methoxyoxetane δ‐amino ester with d‐lyxo configuration 7. The analogous procedure for d‐ribono‐1,4‐lactone 16 furnished a mixture of d‐ribo and d‐arabino esters 17 and 18. Hydrolysis of the methyl esters 7, 17, and 18 to their corresponding δ‐amino acids was successful with LiOH in THF, in contrast to that of their 3‐hydroxy analog 11.      

Mild and Efficient Synthesis of Carboxylic Acid Anhydrides from Carboxylic Acids and Triazine Coupling Reagents

Abstract

Anhydrides of carboxylic acids were obtained in 53%–95% yield by treatment of appropriate carboxylic acids with 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine (CDMT) or 2,4‐dichloro‐6‐methoxy‐1,3,5‐triazine (DCMT) in the presence of N‐methylmorpholine. It has been proved that synthesis proceeds via triazine active esters 3a,b, which are able to acylate carboxylate anion but not less nucleophilic carboxylic acid.     

Lewis Acid‐Mediated Addition of Amino Acid‐Substituted α‐Allylsilanes to Aromatic Acetals

Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid‐activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2‐(N‐PG‐amino)‐3‐(trimethylsilyl)pent‐4‐enoate and methyl (E)‐2‐(N‐PG‐amino)‐3‐(trimethylsilyl)hex‐4‐enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl₄ was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl₄ was required to achieve high yields, whereas 2 equiv. of BF₃?OEt₂ were required for comparable outcomes. Excellent selectivity (>99% syn/anti) and high yield (up to 89%) were obtained with halo‐substituted aromatic acetals, while more electron‐rich electrophiles led to both lower yields and diastereoselectivities.     

A Closer Look at the Hydroiodination of Propiolic Acid

The crystal structures of cis‐3‐iodoacrylic acid (1), trans‐3‐iodoacrylic acid (2), trans‐3‐iodoacrylic acid methyl ester (3), 3,3‐diiodopropanoic acid (4), and trans‐2,3‐diiodoacrylic acid (5) are reported. Compounds 1 and 2 are the kinetic and thermodynamic products, respectively, of the hydroiodination of propiolic acid. Compound 4 results from addition of a second equivalent of hydroiodic acid to 1 or 2, whereas 5 results from the addition of trace elemental iodine to propiolic acid.     

Strukturelle Abwandlungen an N-Acetylneuraminsäuren, 8 Synthese von 7-, 8-, 9-Desoxy- und 4,7-Didesoxyneuraminsäure

The 7- and 8-Iodnonulosonic acid derivatives1 and2 react with tributyltinhydride-AIBN to the 7- and 8-deoxy-N-acetylneuraminic acid derivatives3 a and4 a which after hydrolysis give the 7-deoxy-N-acetylneuraminic acid3 b (5-N-acetamido-3,5,7-trideoxy--D-galacto-2-nonulopyranosidonic acid=7-Deoxy-Neu5Ac) and 8-deoxy-N-acetylneuraminic acid4 b (5-N-acetamido-3,5,8-trideoxy--D-galacto-2-nonulopyranosidonic acid=8-Deoxy-Neu5Ac). The 4,8,9-tris-(t-butyldimethylsilyl)-N-acetylneuraminic acid derivative5 a yields after transformation to the 7-O-acetyl compound5 b and partial removing of the protecting groups the derivative5 c. Further reaction with theMitsunobu-reagent and methyliodide affords the 9-Iodocompound6 a which turned to the 8-O-acetylderivative6 b. Subsequent reduction by means of tributyltinhydride yields first the 9-deoxyderivative7 a and after hydrolysis the 9-deoxy-N-acetylneuraminic acid7 b (5-N-acetyl amido-3,5,9-trideoxy-D-glycero--d-galacto-2-nonulopy-ranosidonic acid=9-Deoxy-Neu5Ac). Another synthesis of7 b follows the route8 f 8 g 7 c. The Deoxy-N-acetylneuraminic acid3 b could be prepared also by an alternative procedure using the methyl--8,9-methylethylen-4-O-t-butyldimethylsilyl-N-acetylneuraminic acid methylester8 a via the intermediate compounds8 d and8 e. Application of the 8,9-O-methylethyliden-N-acetylneuraminic acid derivative8 opens an approach to the xanthogenates8 a and8 b which could be reduced to the deoxy-N-acetylneuraminic acid derivatives9 a and10 a. Hydrolysis of10 a yields the 4,7-dideoxy-N-acetylneuraminic acid10 b (5-N-acetamido-3,4,5,7-tetradeoxy--D-lyxo-2-nonulopyranosidonic acid=4,7-Dideoxy-Neu5Ac).

     

Preparation of Phosphonoterephthalic Acids via Palladium-Catalyzed Coupling of Aromatic Iodoesters

The current article reports in detail the preparation of two phosphonoterephthalic acids: 2-phosphonoterephthalic acid (1) and 2,5-diphosphonoterephthalic acid (2). Efficient, scalable syntheses have been developed for both compounds based on Pd-catalyzed coupling reactions of iodinated terephthalate esters. Phosphonoterephthalic acids are potentially useful as flame-retardant additives or as monomers for the construction of acid-pendant polymer chains.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Two New Disulfated Triterpenoids from Zygophyllum fabago

From the aerial parts of Zygophyllum fabago, two new monosodium salts of sulfated derivatives of ursolic acid, along with two known quinovic acid glycosides were isolated. The structures of the new compounds were determined as (3β,4α)‐3,23,30‐trihydroxyurs‐20‐en‐28‐al 3,23‐di(sulfate) sodium salt (1 : 1) ( 1 ) and of (3β,4α)‐3,23,28‐trihydroxyurs‐20‐en‐30‐yl β‐D ‐glucopyranoside 3,23‐di(sulfate) sodium salt (1 : 1) ( 2 ) with the molecular formula C₃₀H₄₇NaO₁₀S₂ and C₃₆H₅₉NaO₁₅S₂, respectively. The structures of the known compounds were 3‐O‐(2‐O‐sulfo‐β‐D ‐quinovopyranosyl)quinovic acid 28‐β‐D ‐glucopyranosyl ester ( 3 ) and 3‐O‐(β‐D ‐glucopyranosyl)quinovic acid 28‐β‐D ‐glucopyranosyl ester ( 4 ) (quinovic acid=(3β)‐3‐hydroxyurs‐12‐ene‐27,28‐dioic acid). The structures of all these compounds were determined by using 1D‐ and 2D‐NMR spectroscopic techniques.     

Expeditious Synthesis of Ramipril: An Angiotensin Converting Enzyme (ACE) Inhibitor

We document an efficient and cost‐effective synthesis of ramipril 1 utilizing (i) an environmentally benign process for the esterification of racemic 2‐aza‐bicyclo‐[3.3.0]‐octane‐3‐carboxylic acid hydrochloride 2 using boric acid as a catalyst and (ii) a robust resolution process for the synthesis of 3a by means of inexpensive and recyclable L‐(+)‐mandelic acid as key steps.     

Dibromomethane as One‐Carbon Source in Organic Synthesis: Formal Total Synthesis of (±)‐Nephrosteranic Acid

A diastereoselective formal total synthesis of (±)‐nephrosteranic acid (10) is described. The key step is to introduce the α‐methylene group by the ozonolysis of monosubstituted alkenes followed by reaction with a preheated mixture of CH₂Br₂–Et₂NH. The α‐methyl group of compound 10 was formed from the reduction of the corresponding α‐methylene precursor.     

Synthesis and helical conformation of poly(N‐propargylamides) carrying L‐aspartic acid in the side chain

Aspartic acid‐based novel poly(N‐propargylamides), i.e., poly[N‐(α‐tert‐butoxycarbonyl)‐L ‐aspartic acid β‐benzyl ester N′‐propargylamide] [poly( 1 )] and poly[N‐(α‐tert‐butoxycarbonyl)‐L ‐aspartic acid α‐benzyl ester N′‐propargylamide] [poly( 2 )] with moderate molecular weights were synthesized by the polymerization of the corresponding monomers 1 and 2 catalyzed with (nbd)Rh⁺[η⁶‐C₆H₅B^?(C₆H₅)₃] in CHCl₃ at 30 °C for 2 h in high yields. The chiroptical studies revealed that poly( 1 ) took a helical structure in DMF, while poly( 2 ) did not in DMF but did in CH₂Cl₂, CHCl₃, and toluene. The helicity of poly( 1 ) and poly( 2 ) could be tuned by temperature and solvents. Poly( 2 ) underwent solvent‐driven switch of helical sense, accompanying the change of the tightness. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5168–5176, 2005     

Determination of L- and D-2-Halopropanoic Acids and 2-Halobutanoic Acids with Bacterial Dehalogenases

Abstract

A simple method for the enantioselective determination of 2-halopropanoic acids and 2-halobutanoic acids with two bacterial 2-halo acid dehalogenases has been developed. L-2-Halo acid dehalogenase acts specifically on L-2-haloalkanoic acids, and DL-2-halo acid dehalogenase acts on both enantiomers of the acids. The dehalogenation was followed by determination of halogen ions released. Linear relationship was established between the absorbance at 460 nm, and the amounts of L-2-haloalkanoic acids (0.025-0.5 μmol) or the racemates (0.05-1.0 μmol). The D-isomers were estimated by subtracting the amounts of L-isomers from those of DL-2-haloalkanoic acids.     

Lewis Acid or Brønsted Acid Catalyzed Reactions of Vinylidene Cyclopropanes with Activated Carbon–Nitrogen,Nitrogen–Nitrogen,and Iodine–Nitrogen Double‐Bond‐Containing Compounds

Lewis acid or Brønsted acid catalyzed reactions of vinylidene cyclopropanes (VDCPs), 1 , with activated carbon–nitrogen, nitrogen–nitrogen, and iodine–nitrogen double‐bond‐containing compounds have been thoroughly investigated. We found that pyrrolidine and 1,2,3,4‐tetrahydroquinoline derivatives can be formed in good yields in the reactions of VDCPs 1 with ethyl (arylimino)acetates 2 by a [3+2] cycloaddition or intramolecular Friedel–Crafts reaction pathway. Based on these results, we found that activated carbon–nitrogen and nitrogen–nitrogen double‐bond‐containing compounds, such as N‐toluene‐4‐sulfonyl (N‐Ts) imines 5 and diisopropylazodicarboxylate ( 7 ), can also react with VDCPs 1 to give [3+2] cycloaddition products in moderate to good yields in the presence of a Lewis acid. When N‐tert‐butoxycarbonyl aldimine 9 was used as the substrate, six‐membered cycloaddition products 10 and 11 were formed in moderate yields in the presence of a Brønsted acid, trifluoromethanesulfonic acid (TfOH). The reactions of VDCPs 1 with N‐Ts‐iminophenyliodinane ( 12 ) were also carried out in the presence of (CuOTf)₂ ? C₆H₆ and it was found that nitrogen‐containing indene derivatives 13 were obtained, rather than the aziridination products. Plausible mechanisms for all of these transformations are discussed, based on the obtained results.     

A Preferred Synthesis of 1,2,4‐Oxadiazoles

Abstract

An efficient and high‐yielding one‐pot synthesis of 1,2,4‐oxadiazoles from carboxylic acids and amidoximes is described. Activation of the carboxylic acid using hydroxybenzotriazole (HOBt) and EDC/HCl followed by reaction with an amidoxime generates an oxime ester. Without isolation, the oxime ester is dehydrated to give the oxadiazole ring.     

Synthesis of Chiral Nitrones from N‐Fmoc Amino Acids and N‐Fmoc Dipeptides

Abstract

In this work is presented a synthetic procedure for the preparation of chiral nitrones from N‐Fmoc protected amino acids and dipeptides. The nitrone functional group can replace the carboxyl unit of amino acid and peptide systems and can be inserted into the peptide chain. The introduction of the 1,3‐dipole in peptide segments can improve the solubility and the stability toward enzymatic degradation.     

Terpenoids of Linaria alpina (L.) Mill. from Dolomites,Italy

This paper reports the first phytochemical analysis of Linaria alpina (L.) Mill., collected in Dolomites (Italy), a species characteristic of mountain environment. Besides aucubin (4), which is rare in the subgenus Antirrhineae of Plantaginaceae, mainly acidic compounds were found, i.e. oleanolic acid (1), ursolic acid (2) maslinic acid (3) and shikimic acid (5). The pentacyclic triterpenes of L. alpina resulted in relatively high content, whereas flavonoids resulted in low content.     

Novel Synthesis of 5‐Substituted‐3‐phenylindole‐2‐(1,2,4‐triazole) Derivatives

Various substituted 3‐phenylindole 2‐carboxylates (1a–c) were prepared according to the literature methods. These carboxylates (1a–c) on reaction with thiosemicarbazide yielded 5‐substituted‐3‐phenylindol‐2‐(1,2,4‐triazole‐3‐thione) (2a–c) on refluxing in pyridine for 8 h. The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐thioacetic acid] (3a–c) were prepared from 5‐substituted‐3‐phenyl indole‐2‐[1,2,4‐triazole‐3‐thione] (2a–c) on reaction with an appropriate alkylating agent and sodium acetate in acetic acid. Further, (3a–c) were reacted with acetic anhydride to bring about a cyclocondensation reaction to yield 5‐substituted‐3‐phenylindol‐2‐thiazolo(2,3‐b)‐triazole (4a–c). The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐acetic acid] (3a–c) were reacted with o‐phenylenediamino dihydrochloride in ethylene glycol to yield 5‐substituted‐3‐phenylindole‐1,2,4‐triazolo‐3′‐yl‐thiomethyl)benzimidazoles (5a–c).