Amino-acid sequence study in peptides by mass spectometry-II. Investigation of pentadeuterobenzoyl-peptide methyl esters

The utility of benzoyl and pentadeuterobenzoyl derivatives of peptide methyl esters for mass spectrometric analysis was investigated. The mass spectra of the glu-his and the val-tyr-pro derivatives are discussed. Treatment of the peptide methyl esters with the mixed benzoic-ethyl-carbonic anhydride did in some cases lead to benzoyl derivatives as well as to ethoxycarbonyl derivatives.     

Synthesis of β,β-branched β-amino ester derivatives through spiroaziridination of (α-trimethylsilanylmethyl)cyclohexylidene esters

The reaction of (α-trimethylsilanylmethyl)cyclohexylidene esters with NsONHCO₂Et and CaO produces the N-(ethoxycarbonyl)spiroaziridines which, after ring-opening, gives the corresponding β,β-disubstituted β-amino ester derivatives. The stereochemical outcome of the reaction is influenced by substituents on the cyclohexyl group.     

Investigation the chemical reactivity of positions N‐3, C‐5 and C6‐methyl group in biginelli type compounds and synthesis of new dihydropyrimidine derivatives

The compounds 5‐ethoxycarbonyl‐1,6‐dimethyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (5) and 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(lH)‐one (1) were prepared by the Biginelli condensation method and they converted to eight N‐3 substituted dihydropyrimidines using NaH and various electrophiles (ClCO₂Et, TsCl, Ac₂O, AcCl and PhCOCl). Compound (1) was mono‐brominated at the C₆‐methyl group using bromine solution. Reaction of the bromo derivative with amino nucleophiles such as methyl amine and cyclohexyl amine produced two pyrrolo‐pyrimidine derivatives. All the compounds except 5‐ethoxycarbonyl‐1‐phenyl‐6‐methyl‐4‐(3‐nitrophenyl)‐3,4‐dihydropyrimidin‐2(l_H)‐one ( 4 ) were purified by recrystallization methods. The structure of all the new compounds was confirmed using FT‐ir,¹H nmr, ¹³C nmr spectral and elemental analyses methods.     

A comparative study of the reactions of thiophene-2-carboxanilides and related compounds

Thiophene-2-carboxanilide and itsp-chloro andp-bromo derivatives react with chlorosulfonic acid to give the corresponding sulfonyl chlorides, which react with amino acids to give the respective derivatives. Several methyl esters of the latter were prepared. Hydrazinolysis of these methyl esters yielded the hydrazides. Coupling reactions of some sulfonylamino acids with amino acid methyl ester hydrochlorides in THF-Et₃N medium using the dicyclohexylcarbodiimide method give the corresponding dipeptide methyl esters. The spectral data of the compounds are briefly discussed.Chemistry Department, Faculty of Science, Al Azhar University, Nasr City, Cairo, Egypt. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 921–926, July, 1998.     

Synthesis of Some Novel Benzylidenehydantoins: Amino Acids Derivatives

5-Benzylidenehydantoin reacts with chlorosulfonic acid to give the corresponding p-sulfonyl chloride. Condensation of the latter with amino acids leads to sulfonylamino acid derivatives, which on coupling with glycine methyl ester hydrochloride in THF-Et₃N using the dicyclohexylcarbodiimide method furnish the desired dipeptide methyl esters. The spectral data of the compounds are briefly discussed.     

Ester der Imidodiphosphorsäure

Imidodiphosphoric Acid Esters Imidodiphosphoryl tetrachloride reacts with aliphatic alcohols (C₁–C₃) as well as with sodium phenolate to form tetraalkylesters or tetraphenylesters of the imidodiphosphoric acid, resp. The tetraalkylesters (alkyl = methyl, ethyl, n-propyl) are also formed by reaction of trichlorphosphazene phosphoryldichloride, Cl₃P?N? POCl₂, with the corresponding alcohols. The purification of the esters can be reached by destillation of their silyl derivatives followed by desilylation. The esters are associated by intermolecular O…?H…?O hydrogen bonds.     

GC-MS analysis of hydroxy and epoxy acids from seed oil of Hippophaë rhamnoides

By the GC-MS method using a packed column, in the mixture of TMS derivatives of hydroxy acid methyl esters obtained from the seed oil of the sea buckthorn, in ten chromatographic peaks (CPs) 13 monohydroxy compounds have been characterized by their mass spectra, the main ones being derivatives of dimorphecolic and coriolic acids. Structures are proposed for four dihydroxy acids of the C₁₇–C₂₀ series. The mixture of methyl esters of di- and tetra-TMS derivatives obtained from the mixture of epoxy acids from the same source has been analyzed by a similar method. In seven CPs, 11 compounds, reflecting the presence of nine epoxy acids in the initial mixture, have been characterized by their mass spectra. The main component of the mixture was 15,16-epoxyoctadeca-9,12-dienoic acid.     

Thermal Decomposition of Fullerene Derivatives A Synthesis Method of New Fullerene Based Molecules

The thermal decomposition of methano-fullerene derivatives such as ethoxycarbonyl methano[60] fullerene and various isomers of bis-(ethoxycarbonyl methano)[60] fullerene leads to new fullerene derivatives, which have been preliminary characterized. The analysis of separated species was performed by UV-VIS, IR, H- and C-NMR, STM, FAB, LDI and MALDI-TOF MS spectroscopy. One of the isolated phases is a C₁₂₂ molecule with a dumbbell-like structure. This revised version was published online in July 2006 with corrections to the Cover Date.     

GC-MS analysis of hydroxy and epoxy acids from seed oil of Hippopha? rhamnoides

By the GC-MS method using a packed column, in the mixture of TMS derivatives of hydroxy acid methyl esters obtained from the seed oil of the sea buckthorn, in ten chromatographic peaks (CPs) 13 monohydroxy compounds have been characterized by their mass spectra, the main ones being derivatives of dimorphecolic and coriolic acids. Structures are proposed for four dihydroxy acids of the C₁₇–C₂₀ series. The mixture of methyl esters of di- and tetra-TMS derivatives obtained from the mixture of epoxy acids from the same source has been analyzed by a similar method. In seven CPs, 11 compounds, reflecting the presence of nine epoxy acids in the initial mixture, have been characterized by their mass spectra. The main component of the mixture was 15,16-epoxyoctadeca-9,12-dienoic acid.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 626–634, September–October, 1989.     

Electron impact ionization mass spectra of 2,4,5,5-tetrasubstituted 1,2,4-triazolidine-3-thiones. The effect of the ethoxycarbonyl group at position 4

The electron impact ionization mass spectra of 2,4,5,5-tetrasubstituted 1,2,4-triazolidine-3-thiones studied confirmed that the substituent at position 4 has the most dramatic influence on the fragmentation pattern. When the substituent is a methylallyl group the molecular ions exhibit four main routes of fragmentation, but when it is an ethoxycarbonyl/acetyl or a methyl group these direct decompositions of the molecular ion become less abundant. Interestingly all 4-ethoxycarbonyl derivatives and the 4-acetyl derivative exhibited the ions [M-R⁴-COOC₂H₄]⁺ and [M-R⁴-COCH₂]⁺, respectively, with the same composition.     

Chemistry of heteroanalogs of isoflavones

Condensation of cyanomethyl derivatives of benzimidazole and benzothiazole with resorcinol gave the corresponding 2,4-dihydroxy-α-hetarylacetophenones. The latter were converted to 3-hetarylchromones with methyl, trifluoromethyl, and ethoxycarbonyl groups in the 2 position or to chromones without substituents in this position.     

NbCl5 mediated deprotection of methoxy methyl ether

An efficient cleavage of methoxy methyl ether using NbCl₅ is described. This protocol works efficiently with MOM ethers of alkyl, allyl, propargyl, benzyl alcohol and phenol derivatives. MOM esters are also found to be effectively cleaved under the present conditions.     

13C NMR chemical shifts of N-unsubstituted- and N-methyl-pyrazole derivatives

¹³C shielding data for 100 derivatives of pyrazole are reported. These include methyl, ethyl, n-propyl, tert-butyl, phenyl, hydroxymethyl, carboxyl, ethoxycarbonyl, cyano, amino, hydrazino, nitro, azido, chloro, bromo and iodo groups as substituents on the ring carbon atoms.     

Simple and condensed β-lactams-I : The application of diketene in β-lactam synthesis. The synthesis and functional group manipulations of diethyl 3-acetyl-4-oxoazetidine-2,2-dicarboxylates

Acylation of the N-substituted diethyl aminomalonates 3a–3d with diketene furnished the ring tautomers 6a–6d of the expected acetoacetyl derivatives 5. By treatment with iodine and sodium ethoxide compounds 6a–6d are smoothly converted into the β-lactam derivatives 2a–2d. Deethoxycarbonylation of the ethylene ketals 7a–7d of the latter furnishes mixtures of the corresponding diastereomeric monoesters 8 and10. The ethoxycarbonyl groups of the trans esters 8 are more reactive than those of the cis isomers 10. This permits, under appropriate conditions, selective alkaline hydrolysis and NaBH₄ reduction of the trans esters 8 in the presence of the cis esters 10. Reduction of the cis ester 10c under more forceful conditions furnishes the trans hydroxymethyl derivative 11c.     

Interaction of Hydroxylamine with Esters of 2-Oxobutenoic Acids. Synthesis of 1-Hydroxy-3-hydroximino-2-pyrrolidinones

New 3-hydroximino-1-hydroxy-2-pyrrolidinones have been synthesized by the interaction of NH₂OH and NH₂OBn with the methyl esters of 2-oxo-3-butenoic acid derivatives. Some intermediate compounds have been isolated and identified and the reaction mechanism is discussed.     

Synthesis of gibberellins A8 and A56 from gibberellin A3

A mixture of gibberellin A₃ derivatives with 1(10)-ene-2β,3β-diol and 1(10)-ene-2α,3β-diol (2:5) groups, readily obtained from gibberellin A₃, has been used for a new and simple synthesis of gibberellin A₈ and its esters. The hydrolysis of GA₃ and the iodolactonization of a mixture of the 2-epimers was carried out in aqueous solution in a single flask, as also was a synthesis of GA₅₆ from GA₃ by a method that we have modified. The mixture of 1β-iodides of GA₈ and GA₅₆ was separated by chromatography on SiO₂ in the form of methyl or p-bromophenacyl esters which were then deiodinated and the methyl or p-bromphenacyl ester of GA₈ was isolated. Free GA₈ was obtained by the dephenylation of the latter ester. By two-dimensional NMR spectroscopy we succeeded in assigning all the signals in the¹³C and¹H NMR spectra of the methyl esters of GA₈ and GA₅₆. In an attempt to obtain GA₅ methyl ester by the action of trimethylchlorosilane/sodium iodide on the 2α,3β-diol system in GA₅₆ methyl ester, the 8,13-epimer of the latter was formed, the structure of its molecule being established from the results of X-ray structural analysis.     

Convenient One‐Pot Protocol for an Exclusive Synthesis of 4‐Cyano/ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromene and/or 3‐Cyano/ethoxycarbonyl‐2‐isopropyl‐benzo[b]furan from a Single Oxo‐ylide

[{2‐(Fluoroaryloxy)‐2‐methyl‐propanoyl}‐(cyano/ethoxycarbonyl) methylene]triphenylphosphoranes underwent microwave‐assisted tandem intramolecular Wittig and Claisen rearrangement and internal cyclization reactions to afford fluoro‐substituted 2,2‐dimethyl‐2H‐chromenes and/or 2‐isopropyl‐benzo[b]furans in good yield. Upon controlled microwave irradiation in the presence of Nafion H catalyst in xylene, the oxo‐ylides selectively formed 4‐cyano/ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromenes. Microwave irradiation of the same oxo‐ylide in the presence of K₂CO₃ as catalyst or in a polar solvent–like sulfolane resulted in the exclusive formation of the corresponding fluoro‐substituted 3‐cyano/ethoxycarbonyl‐2‐isopropyl‐benzo[b]furans.     

Chinazolincarbonsäuren. XII. Mitteilung. Synthese von [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxochinazolin-3-yl]-, [2-(Ethoxycarbonyl)chinazolin-4-yloxy]- und (5,6,7,8-Tetrahydro-2-phenylchinazolin-4-ylthio)alkansäure-estern

Quinazolinecarboxylic Acids. Synthesis of Alkyl [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-yl]-, [2-(Ethoxycarbonyl)quinazolin-4-yloxy]- and (5,6,7,8-Tetrahydro-2-phenylquinazolin-4-ylthio)alkanoates The [(2-aminobenzoyl)amino]alkanoic acids and their esters 1 showed a different reaction behaviour with diethyl oxalate. Compound 1 (n = 2,3) was converted into the quinazolinylalkanoates 3 . o-Aminohippurate yielded with ethyl (chloroformyl)formate a mixture of the amide 4 and the cyclized quinazolinone 7b . Ethyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate ( 6 ) reacted with 2-bromoalkanoates, in the presence of NaH, to the [2-(ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-y1]acetates 7 in the case of alkyl bromoacetate, and to the O-alkylated derivatives 8 with the ethyl 2-bromopropionate and -butyrate. 2-Aminobenzamide ( 5 ) gave with ethyl 3-(chloroformyl)-2-propenoate and methyl 3-(chloroformyl)propionate the amides 9 or 11 , respectively, and not the expected quinazolinones. The cyclized product 12 was obtained from 11 and ethyl bromoacetate. Tetrahydroquinazolin-4(3H)-thione 14 was synthesized by the reaction of 13 with NH₃, and it was alkylated at the S-atom with bromoalkanoates to 15 . The hydrazide 16 was synthesized from 15b with hydrazine hydrate.     

Synthesis of 2,4-diamino-5-acetyl(ethoxycarbonyl)pyrimidines from β-dicarbonyl compounds and dicyandiamide and their use for building a pyrimido[4,5-d]pyrimidine system

2,4-Diamino-5-acetyl(ethoxycarbonyl)-6-methyl(phenyl)pyrimidines were obtained by the reaction of acetylacetone and -ketocarboxylic acid esters with dicyandiamide in the presence of Ni(OAc)₂. It was shown that annelation of the pyrimidine ring with this compound provides a convenient method for building the pyrimido[4,5-d]-pyrimidine system. New derivatives of 2-aminopyrimido[4,5-d]pyrimidine, 7-amino-3H-pyrimido[4,5-d]-pyrimidin-4-one, and 7-amino-1H,3H-pyrimido[4,5-d]-pyrimidine-2,4-dione were synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 159–164, January, 1991.     

Synthesis of carboxylic acids based on the closo-decaborate anion

A series of new boron-containing carboxylic acids was prepared by the ring-opening reaction of cyclic oxonium derivatives of the closo-decaborate anion [B₁₀H₁₀]²⁻ with methyl esters of hydroxybenzoic acids or the cyanide anion followed by hydrolysis of the obtained nitrile and esters. Acid hydrolysis of the esters results in protonation of the oxygen atom connected to the boron cage, with the formation of the corresponding O-protonated acids, isolated in the solid state. The compounds synthesized can be used in radionuclide diagnostics and boron neutron capture therapy of cancer.