The synthesis of azahomotryptophane derivatives. The transformation of N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester into 4-(imidazo[1,2-a]azinyl-3)-4-oxohomoalanine derivatives

Azatryptophane homologues, 4-(imidazo[1,2-a]pyridinyl-3)- 9a-9f and 4-(imidazo[1,2-a]pyrimidinyl-3)-4-oxohomoalanine derivatives 9g-91 , were prepared from N,N-dimethyl-N′-(pyridinyl-2)- 6a-6f and N,N-dimethyl-N-(pyriniidinyl-2)formamidines 6g-6i , and (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester ( 2 ) and its (R,S)-isomer.     

<Emphasis Type="Italic">N</Emphasis>-trifluoroacetyl-β-alanine in the synthesis of carnosine

Conditions have been developed for the synthesis of N-trifluoroacetyl-β-alanine, N-tifluoroacetyl-β-alanyl chloride, and N-trifluoroacetyl-β-alanine 4-nitrophenyl ester. These compounds reacted with histidine methyl ester or sodium salt to give N-trifluoroacetyl-β-alanyl-l-histidine methyl ester CF₃CONHCH₂CH₂·CONHCH(CH₂C₃H₃N₂)COOCH₃ and N-trifluoroacetyl-β-alanyl-l-histidine CF₃CONHCH₂CH₂CONHCH·(CH₂C₃H₃N₂)COOH. Their hydrolysis with a solution of sodium hydroxide in aqueous ethanol, followed by acidification with trifluoroacetic acid, led to the formation of β-alanyl-l-histidine (l-carnosine).     

Synthesis and biological activity of some new 3-and 6-substituted coumarin amino acid derivatives. Part I

The synthesis of 6-nitrocouarrain-3-CO-amino acids and their corresponding methyl esters (II-XVII) and some dipeptide methyl esters (XVIII-XXVI) are described. 6-(N-Tosyl- or N-phthalylaminoacyl)aminocoumarin-3-carboxylic acid methyl esters (XXXIV-XL) and 3-(N-phthalyl- or N-tosylaminoacytyaminocoumarins (XLV-LVI) have been prepared via the carbodiimide and acid chloride methods. Hydrazinolysis of 3- or 6-(N-phthalylaminoacyl)aminocoumarin derivatives in tetraline gave the corresponding 3- and 6-(aminoacyl)aminocoumarins and the carboxylic acid hydrazides (XLI-LVIII), respectively. 3-(N-Tosyl-L-Val-L-Leu-)aminocoumarin (LIX) was synthesized via the azide method. Twenty four of various substituted 3- and 6-aminoacylcoumarin derivatives were found to possess specific antimicrobial activities towards different microorganisms.     

Reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles. Synthesis of δ-hetaryl-substituted α-amino acids

The reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles afforded -hetaryl-N-trifluoroacetyl-substituted -amino acids (hetaryl is thiazol-2-yl, 2-thienyl, or thieno[2,3-b]pyridin-6-yl).     

2-Benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxy-carbonylvinyl-1 as N-protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N-terminal 3-heteroarylamino-2,3-dehydroalanine

Ethyl 2-benzoyl-3-dimethylaminopropenoate ( 6 ) and methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with α-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-α-amino acids 13–19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycar-bonylvinyl-1)-protected dipeptide esters 20–31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo-rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) by glycine gave N-(2-benzoylamino-2-methoxycar-bonylvinyl-1)glycine ( 47 ), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester ( 48 ). Treatment of 48 with 2-arnino-4,6-dirnethylpyrimi-dine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71–82, and pentapeptide esters 83–85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58–85.     

Room-temperature polycondensation of β-amino acid derivatives VI. Synthesis of various N-(hydroxyethyl) nylons

Various N-(hydroxyethyl)amino acid esters having a methyl substituent or phenyl group between amine and ester groups have been synthesized and their polycondensation behavior was investigated. These substituted amino acid esters gave amorphous polyamides which were soluble in alcohol. A model reaction between N-(hydroxyethyl)-amine and carboxylic acid ester was carried out in order to elucidate the role of hydroxyethyl group on the polycondensation. It was found that the amidation reaction took place rapidly at room temperature when the alkyl group of the carboxylic acid was small. N-(Hydroxyethyl) polyamides were obtained from N,N′-(bishydroxyethyl)-dicamines and dicarboxylic acid esters. The reaction mechanism of the room-temperature polycondensation reaction is discussed.     

The preparation of N-carboalkoxypyrazoles and N-phenylpyrazoles from C(α)-dianions of carboalkoxyhydrazones and phenylhydrazones

The 1,4-dianions of C(α),N-carboalkoxyhydrazones and C(α),N-phenylhydrazones were prepared in an excess of lithium diisopropylamide (LDA). These dilithiated intermediates resulted from metalation of substituted hydrazones of several all-aliphatic cyclic ketones, aliphatic-aromatic cyclic ketones phenylacetaldehyde, and several substituted propiophenones or acetophenones. The esters utilized for Claisen-type condensations of these dianion intermediates included methyl salicylate, methyl p-hydroxybenzoate, methyl nicotinate and related materials. The condensations were followed by acid-cyclizations to give a variety of N-phenylpyrazoles and N-carboalkoxypyrazoles, most of which are new.     

Synthesis of 1,2-Diamino-1-phenylpropane Diastereoisomers from <Emphasis Type="Italic">u</Emphasis>-<Emphasis Type="Italic">N</Emphasis>-Trifluoroacetyl-2-amino-1-phenylpropan-1-ol

Summary. A new simple procedure for the synthesis of diastereomeric 1,2-diamino-1-phenylpropanes starting from u-N-trifluoroacetyl-2-amino-1-phenylpropan-1-ol (N-trifluoroacetylnorephedrine) is described. The trifluoroacetyl protecting group was particularly suitable for the protection of the amino group in order to reduce side reactions.     

Synthesis of 1,2-Diamino-1-phenylpropane Diastereoisomers from u-N-Trifluoroacetyl-2-amino-1-phenylpropan-1-ol

A new simple procedure for the synthesis of diastereomeric 1,2-diamino-1-phenylpropanes starting from u-N-trifluoroacetyl-2-amino-1-phenylpropan-1-ol (N-trifluoroacetylnorephedrine) is described. The trifluoroacetyl protecting group was particularly suitable for the protection of the amino group in order to reduce side reactions.     

1,6- and 1,7-naphthyridines. II. Synthesis from acyclic precursors

A number of 8-hydroxy-6-methyl-1,6-naphthyridin-5(6H)-one-7-carboxylic acid alkyl esters 3 and the isomeric 5-hydroxy-7-methyl-1,7-naphthyridin-8(7H)-one-6-carboxylic acid alkyl esters 4 were synthesized from acyclic precursors obtained starting from quinolinic anhydride 5. Thus, methanolysis of 5 afforded the hemiester 6 which treated with oxalyl chloride and sarcosine ethyl ester gave 3-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-2-carboxylic acid methyl ester 8. Compound 8 was cyclized to naphthyridines 3a-e with sodium alkoxides. The isomeric naphthyridines 4a-c were obtained by cyclization of the open intermediary 2-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-3-carboxylic acid methyl ester 9 obtained by a route that involves treatment of 5 with sarcosine ethyl ester and esterification with diazomethane. Spectroscopic properties (¹H nmr, uv, ir) of compounds 3 and 4 are discussed and confirmed the proposed structures.     

Phthalimide as a chromophoric tag in the circular dichroism determination of absolute configuration of α-aminoacid amides and dipeptides. A case of a dipeptide isostructurality

Both N-phthaloyl aminoacid amides and methyl amides as well as N-phthaloyl dipeptide methyl esters give Cotton effects of opposite signs at around 220 and 240 nm. The signs of these Cotton effects are directly correlated with the absolute configuration of the N-phthaloyl substituted stereogenic center: for -configuration the Cotton effect at 240 nm is positive and the Cotton effect at 220 is negative. The X-ray analysis shows that the diastereomeric , and , N-phthaloyl alanylvaline methyl esters form isostructural orthorombic crystals due to the conformational flexibility of the molecules and a similar space requirements of the methoxycarbonyl and isopropyl groups.     

Mass spectrometry of some methyl esters of N-4-pyrimidinylamino acids: Rearrangements of the ions occurring on electron-impact ionization

The electron-impact-induced mass fragmentations of methyl esters of N-(1H-2-oxo-4-pyrimidinyl)ainino acids are reported. The loss of a ·COOCH₃ radical and the elimination of a methanol molecule were observed and possible mechanisms of these processes are proposed. The loss of a ·COOH radical and elimination of water were established, which suggests the rearrangement of the investigated esters into isomeric N-4-pyrimidinylamino acids.     

1,2,3-thiadiazoles. I. Synthesis of sodium (or potassium) 1,2,3-thiadiazole-4-thiolates via thiocarbazonate esters and N-acylthiohydrazonate esters

A general synthesis of 1,2,3-thiadiazole-4-thiolates 1 and their derivatives 2–3 by an extension of the Hurd-Mori 1,2,3-thiadiazole synthesis is described. Treatment of methyl (or ethyl) [1-(alkylthio)alkylidene]hydrazinocarboxylates 11 (thiocarbazonate esters) or other N-acylthiohydrazonate esters [Y = ureido ( 12 ) or arenesulfonyl ( 13 )] with thionyl chloride affords 2–3 efficiently. Intermediates 11–13 are readily obtained from the N²-thioacylcarbazates 8 , N³-thioacylsemicarbazides 9 , or N²-thioacyl-N¹-(p-toluenesulfonyl)hydrazides 10 , respectively, by S-alkylation. Physicochemical properties of the 1,2,3-thiadiazoles 1–3 and N-acylthiohydrazonate esters 11–13 are also described.     

Syntheses and radical polymerization behavior of novel optically active methacrylamides having (L)-leucine structure in the side chains

Syntheses and radical polymerizations of methacrylamides having (L)-leucine and N-methyl-(L)-leucine methyl ester structures in the side chains N-methacryloyl-(L)-leucine methyl ester (MA-L-M) and N-methyl-N-methacryloyl-(L)-leucine methyl ester (N-Me-MA-L-M) were carried out. The monomers were prepared by the reactions of methacryloyl chloride with the corresponding amino acid methyl esters. Radical polymerizations were carried out in the presence of appropriate initiators at 60°C and 120°C. MA-L-M afforded the corresponding polymer with M_ns 38,000 ∼ 372,000 in high yields, while N-Me-MA-L-M afforded a trace amount of polymer at 60°C and in a low yield even at 120°C. Both inversion and increase of absolute value of specific rotation were observed in the transformation from MA-L-M (+1.3°C) to poly(MA-L-M) (−35.7°C). Changes in the CD spectral pattern and the conformation of the leucine moiety were confirmed from the monomer to polymer. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2681–2690, 1998     

Carbon-13?proton coupling constants in N-substituted imidazoles. A 13C NMR study and MO calculations

The ¹³C NMR data of imidazole, and N-methyl-, N-acetyl-, N-trifluoroacetyl-, N-heptafluorobutyryl- and 2-methyl-imidazoles, were obtained from proton-noise decoupled and single frequency NOE ¹³C NMR spectra. The considerable changes in the directly-bonded (C, H) coupling constants upon N-acetylation of the imidazole ring, which are comparable to those noted when going from the neutral to the cationic form of imidazole, are primarily due to the large π-electron transfer ability of the N-acetyl- and N-trifluoroacetyl-substituents. The differences in magnitude of the three-bond (C, H) coupling constants along different paths in the imidazole ring may be attributed to the larger π-contributions across a pyridine-like nitrogen than along a pyrrole-like nitrogen.     

Derivatization of sialic acids for stabilization in matrix‐assisted laser desorption/ionization mass spectrometry and concomitant differentiation of α(2 → 3)‐ and α(2 → 6)‐isomers

Sialylated carbohydrates usually decompose by loss of sialic acid when ionized by matrix‐assisted laser desorption/ionization (MALDI) as the result of the labile carboxylic proton. Stabilization has previously been achieved by forming methyl esters with methyl iodide, a procedure that eliminates the labile proton. In this paper, we describe an alternative procedure for methyl ester formation that provides information on the sialic acid linkage directly from the MALDI spectrum. The sugars were desalted, dissolved in methanol, and treated with 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM). After removal of the solvent, the products were transferred directly to the MALDI target and examined from 2,5‐dihydroxybenzoic acid. Small amounts of N‐glycans derived from biological sources benefited from an additional clean‐up stage involving Nafion 117. α(2 → 6)‐Linked sialic acid produced only methyl esters whereas α(2 → 3)‐linked sialic acids were converted into their lactones providing a 32 Da difference in mass. Negative ion collision‐induced decomposition (CID) mass spectra of these neutralized glycans provided information, in many cases, on the antenna of N‐linked glycans to which the variously linked sialic acids were attached. The method was applied to N‐linked glycans released from bovine fetuin and porcine thyroglobulin. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of N-phosphoryl amino acids using bis(9-fluorenylmethyl)phosphite

Bis(9-fluorenylmethyl)phosphite (BFMP) was found to be an effective reagent for the N-phosphorylation of various amino acid methyl esters. BFMP was prepared from N,N-diisopropyl phosphoramidous dichloride in a one-pot two-step reaction and was obtained as a crystalline solid. N-Phosphorylation of the methyl esters of seven representative amino acids with BFMP was high-yielding and generally resulted in crystalline products. Complete deprotection of both the 9-fluorenylmethylphosphosphate esters and the amino acid methyl esters was accomplished concomitantly with LiOH to give N-phosphoryl amino acids.     

Synthesis of new organothiophosphorus insectoacaricides containingN-acylated amino acid fragments

Methods for the synthesis ofO-alkylS-(N-acyl-N-alkoxycarbonylalkyl)aminomethyl (methyl)thio- and -dithiophosphonates based on the reaction between alkaline-metal salts ofO-alkyl (methyl)thio- and -dithiophosphonates and N-alkoxycarbonyl-N-chloromethylglycine or --alanine esters and by treatment ofO-alkyl (methyl)dithiophosphonoates andN-acylated amino acids or their esters with paraform in the presence of HCl were developed. The compounds obtained exhibit high insectoacaricide activity and selectivity.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1294–1301, July, 1994.     

Reaction of N-Acyl-α-triphenylphosphonio-α-amino Acid Esters with Organic Bases: Mechanism of the Base-Catalyzed Nucleophilic Substitution of the Triphenylphosphonium Group

Summary.  Reactions of N-acyl-α-triphenylphosphonio-α-amino acid methyl esters with organic bases (triethylamine or DBU) were investigated as the crucial step of the base-catalyzed displacement of the triphenylphosphonium group by nucleophiles. It was proved that N-acyl-α-triphenylphosphonioglycinates are transformed to an equilibrium mixture of the corresponding N-acyliminoacetates and N-acyl-α-triphenylphosphoranylidene glycinates by bases. In the case of N-acyl-α-triphenylphosphonio-α-amino acid esters with quaternary α-carbon, the α-substituted homologues of the N-acyliminoacetates were detected to be the only primary reaction product which, however, can undergo further tautomerization to the corresponding α,β-dehydro-α-amino acid derivatives. In both these cases the reaction of N-acyl-α-triphenylphosphonio-α-amino acid esters with nucleophiles proceeds via the addition of a nucleophile to the activated C=N double bond of the N-acylimino intermediate. Corresponding author. E-mail: romanm@zeus.polsl.gliwice.pl Received October 31, 2001. Accepted (revised) December 17, 2001     

酶法拆分(±)-N-(2,6-二甲苯基)-丙氨酸甲酯

用脂肪酶Candida rugosa lipase (CRL)拆分(±)-N-(2,6-二甲苯基)-丙氨酸甲酯, 并进一步优化反应条件. 结果表明, 在加入1 mmol N-(2,6-二甲苯基)-丙氨酸甲酯、100 mL的0.2 mol/L磷酸缓冲液中, CRL拆分该底物的最适反应条件为: pH 6.4, CRL脂酶250 mg, 聚乙二醇(PEG) 2 g, 转速160 r•min^－1, 温度 35 ℃. 其中酶量、温度对转化率影响较大. 反应后分离得R-(＋)-N-(2,6-二甲苯基)-丙氨酸甲酯. 它和酰氯反应可制备一系列旋光性N-酰基丙氨酸类杀菌剂.