Reactions of Quinazoline Alkaloids and their Derivatives with Electrophilic Reagents

Nitration of deoxypeganine (DOP), deoxyvasicinone (DOV), 2,3-tetramethylene-, 2,3-pentamethylene-, and 3,4-dihydroquinazol-4-ones and their 1,2-dihydro derivatives was studied. It was shown that the reaction pathway changed depending on the presence of a carbonyl on C-4 and an N=C bond in these compounds. Only the H atom on C-6 was subject to nitration if both functional groups were present, for example DOV and its homologs. Substitution of the H atom of either the 6-position (DOP, 1,2-dihydro-DOV, and their homologs) or the 6- and 8-positions simultaneously (DOP and its homologs) was enhanced if one of these functional groups was missing depending on the substrate:nitrating agent ratio. The bromination and nitration reactions of 1,2-dihydro-DOV and its analogs in a 1:2 ratio were accompanied by oxidation of the N¹H-CH bond with formation of 6,8-dibromo- and 6,8-nitro-DOV and their homologs. The difference in the behavior of these compounds was due to the different nucleophilicity of the benzene rings in them. The reaction of 1,2-dihydro-DOV and its homologs with isocyanates and p-nitro- and p-methylbenzoic acid chlorides was studied. 6-Nitro- and 6,8-dinitro-DOP and 6,8-dibromo- and 6,8-dinitro-DOV and their homologs and 6-bromo- and 6-nitro-1,2,3,4-tetrahydro-2,3-polymethylenequinazol-4-ones and their 1-alkyl(aryl)-carbamoyl and p-nitro(methyl)-benzoyl derivatives were synthesized. The molecular structures of 1-ethyl-and 1-(o-chlorophenyl)-carbamoyl-1,2-dihydrodeoxyvasicinones and 6,8-dinitro-2,3pentamethylene-3,4-dihydroquinazol-4-one were established. UDC 547.944/945 547.856.1 Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 387-393, July-August, 2008. Original article submitted May 5, 2008.     

Synthesis,methylation, and acylation of 1,2-dihydrodeoxyvasicinones and their homologs

2,3-Trimethylene- and 2,3-pentamethylene-1,2,3,4-tetrahydro-4-quinazolones and their 6-methyl and 6-bromo derivatives have been obtained by the reduction of deoxyvasicinone and its 6-methyl and 6-bromo derivatives and also their seven-membered homologs at the cycloalkane ring with sodium tetrahydroborate in ethanol. The alkylation and acylation reactions of the above-mentioned reducing compounds have been studied. Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 659–663, September–October, 1990.     

Synthesis, methylation, and acylation of 1,2-dihydrodeoxyvasicinones and their homologs

2,3-Trimethylene- and 2,3-pentamethylene-1,2,3,4-tetrahydro-4-quinazolones and their 6-methyl and 6-bromo derivatives have been obtained by the reduction of deoxyvasicinone and its 6-methyl and 6-bromo derivatives and also their seven-membered homologs at the cycloalkane ring with sodium tetrahydroborate in ethanol. The alkylation and acylation reactions of the above-mentioned reducing compounds have been studied.Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 659–663, September–October, 1990.     

Synthetic analogs ofPeganum alkaloids. I. Synthesis of methoxy- and hydroxy-substituted deoxyvasicinones and deoxypeganines

6-Methoxy-, 7-methoxy-, and ′8-methoxydeoxyvasicinones have been synthesized by the reaction of substituted (3-methoxy-, 4-methoxy-, and 5-methoxy-) anthranilic acids with α-pyrrolidone. The demethylation of these compounds has given the corre-sponding hydroxy-substituted analogs of deoxyvasicinone, and the reduction of the products obtained with zinc in hydrochloric acid has given the hydroxy- and methoxy- analogs of deoxypeganine. 8-Hydrooxydeoxypeganine dimethyl-, ethyl-, and butylcarbamates have been obtained by the carbamoylation of 8-hydroxydeoxypeganine.     

Crystal structures of deoxyvasicinone and its salts

The structures of the alkaloid deoxyvasicinone and of its complexes with HCl and CoCl₂·2HCl have been established by the method of x-ray structural investigation. The formation of complex salts of deoxyvasicinone differs from that of alkaloids with similar structures - peganine and deoxypeganine.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 89 14 75. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 849–854, November-December, 1995. Original article submitted April 17, 1995.     

β-Sultams II: Synthesis of tri-, tetra- and pentamethylene- 1,2-thiazetidine 1,1-dioxides

The unsubstituted parent structure of sulfone analogs of penicillin and its higher homologs are obtained by base promoted cyclization of cyclic β-amino-ethanesulfonyl chlorides.     

Reaction of deoxyvasicinone with organolithium compounds

4-Butyl-4-hydroxydeoxypeganine was prepared by lithiation of deoxyvasicinone. Deoxypeganine and 1,2-dihydrodeoxypeganine were produced by reduction of deoxyvasicinone with lithium aluminum hydride.     

Nature of π-Electronic Transitions in UV Spectra of Deoxyvasicinone and Its Derivatives

The principal types of electronic transitions in absorption spectra of deoxyvasicinone and its 6-amino- and 6-nitro-derivatives were determined by analyzing the electron-density distributions in excited states calculated using ZINDO/S.     

Quinazolines XI. Condensation of deoxyvasicinone with aldehydes

Summary In the reaction of deoxyvasicinone with aldehydes, depending on the nature of the substituents of aromatic and heterocyclic aldehydes, and also on the reaction conditions, 9-benzylidene or 9--hydroxybenzyl derivatives of deoxyvasicinone are obtained.Institute of the Chemistry of Plant Substances, Academy of Science of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 552–556, July–August, 1977.     

New reactions of deoxyvasicinone. Part 6

Several acylated derivatives of deoxyvasicinone 1 and its analogues were shown to exist as enols. The 3-hydroxymethyl derivative of 1 was shown to undergo rapid dehydration and products derived from an intermediate 3-methylene compound were obtained. Novel oxazepino analogues of 1 are reported.     

Quinazolines X. Synthesis of 6,6'-methylenebisdeoxyvasicinone and its homologs

Summary 6,6-Methylenebisdeoxyvacisinone and its homologs have been synthesized by the reaction of methylenebisanthranilic acid with lactams (-butyrolactam, -valerolactam, -caprolactam, and -chloro- and ,-dichloro--caprolactams). The condensation of anthranilic acid and its derivatives (4-nitro-, 5-bromo-, 5-iodo-, and 5-nitroanthranilic acids) with ,-dichloro--caprolactam has given seven-membered analogs of deoxyvasicinone containing two chlorine atoms in the polymethylene ring.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 544–547, July–August, 1977.     

Use of multiple-reaction monitoring ratios for identifying incompletely resolved fentanyl homologs and analogs via ultra-high-pressure liquid chromatography–tandem mass spectrometry

Fentanyl and 16 of its corresponding homologs and analogs were distinguished using ultra-high-pressure liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). A 1.7 μm Acquity BEH C18 column (150 mm × 2.1 mm) was used with a 1% formic acid (pH 2.2), methanol gradient. Multiple-reaction monitoring (MRM) was employed for MS/MS detection. All selected fentanyl-related compounds, including incompletely resolved compounds, were uniquely identified using retention times and dual MRMs.     

A quantum-chemical investigation of deoxypeganine and its salts II. The photochemical oxidation of deoxypeganine hydrochloride

The stability of deoxypeganine hydrochloride under the action of light has been established. The kinetics of the oxidation of deoxypeganine hydrochloride in aqueous solution in the presence of deoxyvasicinone hydrochloride have been studied. The structures and electronic conformations of hypothetical models of the salt DOP HCl in the ground and excited states have been considered by the MO LCAO method in the AM1 approximation. The difference in the resistance of the molecules of the base deoxypeganine and its hydrochloride to photochemical oxidation is discussed on the basis of the results of experiments and calculations.Abbreviations HPLC high-performance liquid chromatography - MO LCAO molecular orbitals as linear combinations of atomic orbitals - AM1 Austin Model 1 - DOP HCl deoxypeganine hydrochloride - DOV HCl deoxyvasicinone hydrochloride Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 729–733, September–October, 1993.     

Quantitative analysis of the components of the combined metabolites of deoxypeganine and deoxyvasicinone

The quantitative composition of the combined metabolites isolated from the rat organism after the administration of the anticholinesterase preparation deoxypeganine and its analog deoxyvasicinone has been determined by the mass-spectrometric method of integrating the ion current. The results of the determination have been compared with those obtained by UV spectroscopy.Institute of the Chemistry of Plant Substances, Academy of Sciences of the USSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 201–206, March–April, 1981.     

An Efficient and Convenient Synthesis of Chain Lengthened Homologs of the Fungicide Metalaxyl

An efficient and convenient synthesis of chain lengthened homologs of the important fungicide Metalaxyl is described. The starting material utilized is 2,6-dimethylaniline and the sequence is accomplished utilizing Grignard reactions and ruthenium based oxidations to obtain the proper analogs.     

Synthesis of Spiroheterocyclic Systems from Barbituric Acids and <Emphasis Type="Italic">N,N</Emphasis>-Disubstituted <Emphasis Type="Italic">o</Emphasis>-Aminobenzaldehydes

Reactions of barbituric, 1,3-dimethylbarbituric, and 2-thiobarbituric acids with 2-(1-pyrrolidinyl)benzaldehyde, its 6- and 7-membered homologs, and 4-phenylpiperazine and morpholine analogs lead to formation of fused systems with a spirocyclic 2,4,6-trioxopyrimidine fragment. The process involves intermediate formation of labile 5-arylmethylidenebarbituric acids which exhibit t-amino effect and undergo spontaneous isomerization to give the final products. The observed spirocyclizations are characterized by an anomalously high rate.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 920–925.Original Russian Text Copyright © 2005 by Krasnov, Kartsev.     

New reactions of deoxyvasicinone. Part 3

The reaction of deoxyvasicinone 1 with benzoic anhydride, bis(dimethylamino)methane and amyl nitrite are reported. Metallation of 1 is also described.     

Alkaloids ofNitraria komarovii. XV. Vasicinone and deoxyvasicinone N-oxides

Two new alkaloids have been isolated from the epigeal part ofNitraria komarovii — the N-oxides of vasicinone and of deoxyvasicinone. Their structures have been established on the basis of spectral results and chemical transformations.     

Preparation of deoxypeganine hydrochloride

Details are given of the technology of the synthesis and stagewise analysis of the alkaloids deoxyvasicinone and deoxypeganine hydrochlorides.Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 506–507, July–August, 1990.     

Formylation of deoxyvasicinone by alkylformates: synthesis and reaction of <Emphasis Type="Italic">α</Emphasis>-hydroxymethylidenedeoxyvasicinone with isomeric aminophenols and aminobenzoic acids

A new method for formylation of deoxyvasicinone (DOV) was developed. Nucleophilic substitution of α-hydroxy- and -dimethylaminomethylidene-DOV by isomeric aminophenols and benzoic acids to give α-arylaminomethylidene-DOV was studied.