1,4-Benzodiazepines and their cyclic homologs and analogs

The dependence of the IR and PMR spectral characteristics of 12 compounds of the 1,2-dihydro-3H-1,4-benzodiazepine series on structural and sterochemical factors was studied. Information in favor of concepts regarding the pseudoboat conformation as the primary one for this type of 1,4-benzodiazepine derivative was obtained.     

1,4-Benzodiazepines and their cyclic homologs and analogs

5-Difluoromethylsulfonyl-2-aminobenzophenone was synthesized by condensation of p-difluoromethylsulfonylaniline with benzoyl chloride. 5-Difluoromethoxy- and 5-difluoromethylthio-2-aminobenzophenones were obtained by condensation of phenylacetonitrile with the appropriate p-substituted nitrobenzenes and subsequent reduction of the resulting anthranils. 7-Difluoromethoxy-, 7-difluoromethylthio-, and 7-difluoromethylsulfonyl-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones were obtained by the successive action of bromoacetyl bromide and ammonia on the 2-aminobenzophenone derivatives or by reaction of 2-aminobenzophenones with aminoacetyl chloride hydrochloride. The structure of the 1,4-benzodiazepines was confirmed by a study of the UV, IR, PMR, and mass spectra.     

1,4-Benzodiazepines and their cyclic homologs and analogs

A new method, consisting in the reaction of o-aminobenzophenones with -chloropropionyl chloride and subsequent treatment of the resulting 2-(-chloropropionylamino)benzophenones with ammonia, is proposed for the synthesis of 1,2,3,4-tetrahydro-1,5-benzodiazocin-2-ones.Communications I–VII were published under the title 1,4-Benzodiazepines and Their Derivatives. See [1] for communication VII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1705–1706, December, 1972.     

1, 4-Benzodiazepines and their cyclic homologs and analogs

The physicochemical and pharmacological properties of compounds of eight series of derivatives of 1,2-dihydro-3H-1,4-benzodiazepine have been considered. A marked relationship between the half-neutralization potentials, half-wave potentials of polarographic reduction, and the dipole moments of the compounds with Hammett's constants of the substituents in position 7 has been found. In all the series studied, a tendency is observed to an increase in the physiological activity of the compounds with an increase in the electron-accepting nature of the substituents in position 7.For Communication XI, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1558–1565, November, 1973.     

1,4-benzodiazepines and their cyclic homdlogs and analogs

The transformations (acylation, condensation with aldehydes, and diazotization) of 7- and 3-amino-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones are examined. It is shown that the action of P₂S₅ on 3-acetamidobenzodiazepinone leads to replacement of the oxygen atom of the acetyl group by a sulfur atom. The polarographic reduction of 7-arylideneamino-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones was studied.See [8] for communication 29.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 4, pp. 545–549, April, 1979.     

2-Quinazolinones and their cyclic homologs (review)

Methods for the synthesis of 2-quinazolinones, 1,2-dihydro-3H-1,4-benzodiazepin-2-ones, 1,2,3,4-tetrahydro-1,5-benzodiazocin-2-ones, and 1,2,3,4-tetrahydro-5H-1,6-benzodiazonin-2-ones are examined along with the peculiarities of their structure, their tautomerism, their chemical properties, and their biological activity.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 723–738, June, 1979.     

Synthesis and acid-base properties of phosphorylated diazacycloalkanes and their cyclic analogs

Novel cyclopendant organophosphorus complexing agents,viz. 1,5-bis(2-diphenylphosphorylmethyl (or ethyl))-1,5-diazacyclooctane (1, 2) and l-methyl-4-(2-diphenylphosphorylethyl) piperazine (3), were synthesized on the basis of 1,5-diazacyclooctane and piperazine. The protonation constants of the compounds synthesized and some of their analogs were determined by potentiometric titration in 70 % aqueous ethanol and in nitromethane. The nitrogen atoms of the ring are the protonation sites in all of the systems studied. The regularities of the variation of protonation constants have been explained by the formation of intramolecular hydrogen bonds. The conformational possibilities of the formation of H-bonds in the cations of the ligands have been examined by molecular mechanics.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2007–2012, November, 1994.The authors are grateful to T. V. Timofeeva and N. I. Raevskii for the help in coping with the MMX 88 calculation program and for the discussion of the results.This study was carried out with the financial support of the International Science Foundation (Grant No. MJN 000).     

Histone deacetylase inhibitors: synthesis of cyclic tetrapeptides and their triazole analogs

Synthesis of nine macrocyclic peptide HDAC inhibitors and three triazole derivatives is described. HDAC inhibitory activity of these compounds against HeLa cell lysate is evaluated. The biological data demonstrate that incorporation of a triazole unit improves the HDAC inhibitory activity.     

Synthesis and anticancer activities of proline-containing cyclic peptides and their linear analogs and congeners

A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2?h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC₅₀ of 2.73 and 4.3?µM, respectively compared to their Boc-protected analogs 2a (IC₅₀ 20?µM) and 3c (IC₅₀ 38.51?µM) and cyclic peptides 2 (>100?µM) and 3 (47?µM). These results were further validated by biological experiments such as colony formation and wound healing assays.     

Synthesis of nucleoside analogs of 1,4-oxathiane, 1,4-dithiane,and 1,4-dioxane

The two regioisomers 6-chloro-9-(1, 4-oxathian-3-yl)-9H-purine ( 5 ) and 6-chloro-9-(1,4-oxathian-2-yl)-9H-purine ( 6 ) were obtained when 3-acetoxy-1,4-oxathiane ( 3 ) was subjected to the acid-catalyzed fusion procedure; compound 3 was prepared by a Pummerer reaction with 1,4-oxathiane 4-oxide ( 2 ). The nucleoside analog 6 could he converted into the adenine derivative 7 and 9-(1,4-oxathian-2-yl)-9H-purine-6(1H)thione ( 8 ). The following nucleoside analogs have also been synthesized: 6-chloro-9-(1,4-dithian-2-yl)-9H-purine ( 13 ), 9-(1,4-dithian-2-yl)adenine ( 14 ), 9-(1,4-dithian-2-yl)-9H-purine-6(1H)thione ( 15 ), and 6-chloro-9-(1,4-dioxan-2-yl)-9H-purine ( 18 ).     

Cyclazines and their analogs

Derivatives of a new heterocyclic system, formyl-substituted thiazolopyrimidopyrimidines, are synthesized through reaction of 3-amino-5-methyl-thiazolo[3,2-a]pyrimidinium salts, prepared by alkylation of 2-mercaptopyrimidines with substituted acetonitriies, and the Vilsmeier reagent. These can be used to synthesize polymethine dyes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 692–697, May, 1992.     

Cyclazines and their analogs

The formylation of 2-methyl-6-cyanomethylthiopyridines, 2-methyl-4-cyanomethylthiopyrimidines, or 3-amino-5-methylthiazolopyrimidinium salts gave cyclazine derivatives of new heterocyclic systems with an angular nitrogen atom, which were used for the preparation of polymethine dyes. The relationship of the color and structure of these compounds was studied.For Communication 2, see ref. [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1280–1285, September, 1992.     

Insect pheromones and their analogs

A four-stage asymmetric synthesis of (+)-disparlure [(7R,8S)-(+)-cis-methyl-7,8-epoxyoctadecane (V)] has been effected from 8-methylnon-2Z-en-l-ol (I), obtained by the carboalumination of acetylene with tris(5-methylhexyl)aluminum using the Sharpless reaction. The asymmetric epoxidation of (I), (Ar, mol. sieve A, (+)-DET, (iOPr)₄Ti, t-BuOOH, –15°C, 20 h; H₂O, 1 h, NaOH, –7°C, 30 min) gave 8-methyl-2S,3R-epoxynonan-l-ol (II), which was oxidized (kieselguhr-CrO₃-Py, 0°C, 2 h; 25°C, 2 h) to 8-methyl-2S,3R-epoxynonan-l-al (III). The coupling of (III) with n-C₈H₁₇CH=PPh₃ (–78°C, 1 h; 25°C, 15 h) gave 2-methyl-7R,8S-epoxyoctadec-9Z-ene (IV), the hydrogenation (H₂/5% Pd-C, 25°C, 5 days) of which led to (V) in admixture with an isomerization product. Compound (V) was isolated by HPLC. Substance, yield, [] _D ²⁵ : (II), 73, –2.75°; (III), 80, [80.8°; (IV), 50, +37.25°; (V), 50, +0.8°. The IR and PMR spectra of (II–IV), the¹³C NMR spectra of (II) and (III), and the mass spectrum of (IV) are given.Institute of Chemistry, Bashkir Scientific Center, Urals Branch, Academy of Sciences of the USSR, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 715–718, September–October, 1989.     

Insect pheromones and their analogs

Two methods of synthesizing -geranyl propionate — a component of the sex pheromone of San Jose scale — have been developed: the hydride reduction of the corresponding 6-chloro derivative and the electrochemical reduction of the 6-dimethylsulfonium derivative.For the preceding communication, see [1].Institute of Chemistry, Bashkir Scientific Center, Urals Division, Academy of Sciences of the USSR, Ufa. N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 419–421, May–June, 1989.     

Insect pheromones and their analogs

A highly selective synthesis of 2-methyl-cis-7, 8-epoxyoctadecane — the racemic analog of the sex pheromone of the gypsy moth Porthetria dispar L. — (Z)-disparlure — has been developed that is based on the functionally differentiated partial ozonization of cycloocta-IZ.5Z-diene.Institute of Petroleum and Catalysis, Academy of Sciences of the Republic of Bashkortostan, 450075, Ufa, Prospekt Oktyabrya, 141. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 901–904, November-December, 1995. Original article submitted February 21, 1995.     

Insect pheromones and their analogs

(Z)-hexadec-11-enal and (Z)-hexadec-11-1-yl acetate — components of the sex pheromone of insects of the generaHeliothis andManestra, respectively — have been synthesized by the condensation of undec-10-enal with hex-1-yne, deoxygenation of the heptadec-1-en-12-yn-11-ol formed via the corresponding tosylate to heptadec-1-en-12-yne, and the selective oxonolysis of the latter.Institute of Chemistry, Bashkir Branch, Academy of Sciences of the USSR, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 440–444, May–June, 1987.     

Insect pheromones and their analogs

A four-stage asymmetric synthesis of (+)-disparlure [(7R,8S)-(+)-cis-methyl-7,8-epoxyoctadecane (V)] has been effected from 8-methylnon-2Z-en-l-ol (I), obtained by the carboalumination of acetylene with tris(5-methylhexyl)aluminum using the Sharpless reaction. The asymmetric epoxidation of (I), (Ar, mol. sieve A, (+)-DET, (iOPr)₄Ti, t-BuOOH, ?15°C, 20 h; H₂O, 1 h, NaOH, ?7°C, 30 min) gave 8-methyl-2S,3R-epoxynonan-l-ol (II), which was oxidized (kieselguhr-CrO₃-Py, 0°C, 2 h; 25°C, 2 h) to 8-methyl-2S,3R-epoxynonan-l-al (III). The coupling of (III) with n-C₈H₁₇CH=PPh₃ (?78°C, 1 h; 25°C, 15 h) gave 2-methyl-7R,8S-epoxyoctadec-9Z-ene (IV), the hydrogenation (H₂/5% Pd-C, 25°C, 5 days) of which led to (V) in admixture with an isomerization product. Compound (V) was isolated by HPLC. Substance, yield, [α] _D ²⁵ : (II), 73, ?2.75°; (III), 80, [80.8°; (IV), 50, +37.25°; (V), 50, +0.8°. The IR and PMR spectra of (II–IV), the¹³C NMR spectra of (II) and (III), and the mass spectrum of (IV) are given.     

1,4-Benzodiazepines and their derivatives

A series of compounds of the merocyanine dye type was obtained by the reaction of 1-acetyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones and 1,3-dihydro-2H-1,4-benzodiazepine-2-thiones with 2-methylmercapto-3-ethylbenzothiazolium tosylate, 2-methylmercapto-3,4,5-trimethylthiazolium bromide, 2-methylmercapto-3-methyl-5-phenyloxazolium methosulfate, and 1,3,3-trimethyl-2-formylmethyleneindoline. The hydrogen atoms of the methylene group of the 1-unsubstituted and 1-alkyl-substituted 1,3-dihydro-2H-1,4-benzodiazepin-2-ones are of low mobility, and the indicated compounds do not undergo condensation reactions with electrophilic agents.See [6] for communication VI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 992–994, July, 1971.