Kinetics and mechanism of the N7-hydroxyalkylation of guanosine

The kinetics of the N₇-hydroxyalkylation of guanosine by the equally substituted epoxide, trans-2,3-epoxybutane, and the unequally substituted epoxides, 3-chloro-1,2-epoxypropane, and 1,2-epoxypropane in glacial acetic acid, have been measured by a spectrophotomeric method over the range 20-40°. Activation parameters have been determined. Comparative rates calculated from the ratios of second-order rate constants indicate that 1,2-epoxypropane reacts with guanosine about three times faster than does trans-2,3-epoxybutane and about two times faster than 3-chloro-1,2-epoxypropane. These results coupled with the results of a previous report on the structural analysis of the products from these reactions are consistent with a “push-pull” mechanism in which N₇ of guanosine reacts preferentially at the least substituted carbon of the epoxide with simultaneous transfer of a proton from acetic acid to the oxygen of the epoxide. The lower reactivities of trans-2,3-epoxybutane and 3-chloro-1,2-epoxypropane in comparison to that of 1,2-epoxypropane are discussed in terms of steric factors and electronic factors which determine the stability of the requisite transition state for a “push-pull” mechanism model.     

Mycobacterium E3休止细胞催化烯烃立体选择性环氧化

初步研究了ＭｙｃｏｂａｃｔｅｒｉｕｍＥ３的生长和产酶特性，利用ＭｙｃｏｂａｃｔｅｒｉｕｍＥ３休止细胞催化烷羟化和烯烃环氧化，研究结果表明，烷烃不能被羟化，烯烃环氧化具有底物选择性，对烯丙基型底物ＸＣＨ２ＣＨ＝ＣＨ２（Ｘ＝Ｈ，Ｃｌ，Ｂｒ，ＯＨ）取代基大小显著性环氧化活性，ＭｙｃｏｂａｃｔｅｒｉｕｍＥ３中烯烃单加氧酶和另一种结构未知的酶的存在导致烯烃环氧化过程中存在环氧化物的立体选择性形成和非立体选择     

Three-step synthesis of chiral and sterically hindered amino alcohols based on cyclic enol phosphates

The new synthesis of chiral and sterically hindered 1,2-amino alcohols derivatives of 2-methyl-indane and 1,2,3,4-tethrahydrophenanthrene based on cyclic enol phosphates were investigated. The desired products were obtained using three step procedure: oxidation of accessible enol phosphates, transformation α-hydroxy ketones into corresponding oximes and finally reduction of the last one to 1,2-amino alcohols. The optimal conditions of all stages to obtain products with high enantioselectivity or diastereomeric ratio were found and elaborated. The structures and absolute configurations of (3R)-2,3-dihydro-3-hydroxy-1H-phenanthren-4-one and corresponding oxime were confirmed by X-ray analysis.     

Polycyclic N‐Heterocyclic Compounds. Part 78: Synthesis of N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclohepten‐1‐yl]formamide Oximes and Their Evaluation as Inhibitors of Platelet Aggregation

N‐[2‐([1,2,4]Oxadiazol‐5‐yl)cyclohepten‐1‐yl]formamide oximes were synthesized by fusion of (6,7,8,9‐tetrahydro‐5H‐cyclohepta[1,2‐d]pyrimidin‐4‐yl)amidines with hydroxylamine hydrochloride through a subsequent rearrangement reaction. Effects of the products as well as the structurally related N‐[4‐([1,2,4]oxadiazol‐5‐yl)‐2,3‐dihydro[1]benzoxepin‐5‐yl]formamide oximes and N‐[4‐([1,2,4]oxadiazol‐5‐yl)‐2,3‐dihydro[1]benzothiepin‐5‐yl]formamide oximes on platelet aggregation were evaluated.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. XI. Cyclizations with epoxides

4-Toluenesulfonyl isocyanate cyclized with 1,2-epoxy-3-phenoxypropane and 2,3-epoxypropyl 4-methoxyphenyl ether, respectively, to give 3-(4-toluenesulfonyl)-5-phenoxymethylene-2-oxazolidone ( I ) and 3-(4-toluenesulfonyl)-5-(4-methoxyphenoxymethylene)-2-oxazolidone ( II ). Compounds I and II were hydrolyzed in 2 M sodium hydroxide solution to the corresponding uncyclized hydroxy amides, VII and VIII. Compound I was remarkably stable toward 6 M hydrochloric acid and amines. Styrene oxide, 1,2-epoxybutane, 3-chloro-1,2-epoxypropane, and 1-methoxy-2-methylpropylene oxide reacted with the isocyanate to afford 3-(4-toluene-sulfonyl)-4-phenyl-2-oxazolidone (III), 3-(4-toluenesulfonyl)-4-ethyl-2-oxazolidone ( IV ), 3-(4-toluenesulfonyl)-5-chloromethyl-2-oxazolidone ( V ), and 3-(4-toluenesulfonyl)-4,4-dimethyl-5-methoxy-2-oxazolidone ( VI ), respectively. The yield of VI was constant over a temperature range of 25–90°.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. XII. Cyclizations with epoxides

4-Toluenesulfonyl isothiocyanate reacted with 1,2-epoxy-3-phenoxypropane and 2,3-epoxypropyl 4-methoxyphenyl ether to give, respectively, 3-(4-toluenesulfonyl)-5-phenoxymethylene-2-oxazolidmethione ( I ) and 3-(4-toluenesulfonyl)-5-(4-methoxyphenoxymethylene)-2-oxazolidinethione ( II ) in high yields. The sulfonyl isothiocyanate reacted further with styrene oxide to give a mixture of oxazolidinethiones from which a solid III was isolated. The structure of III is either the 4- or 5-phenyl derivative of 3-(4-toluenesulfonyl)-2-oxazolidinethione. Reactions of the isothiocyanate with 3-chloro-1,2-epoxypropane and 1,2-epoxybutane afforded, respectively, 3-(4-toluenesulfonyl)-5-chloromethyl-2-oxazolidinethione ( IV ) and 3-(4-toluenesulfonyl)-4-ethyl-2-oxazolidinethione ( V ). Evidence for structures was by pmr, ir, and elemental analyses.     

Synthesis of 1,2-Diphenylpyrazolidin-4-ol and its Derivatives

A synthesis of 1,2-diphenylpyrazolidin-4-ol via direct heterocyclization of 1,2-diphenylhydrazine with 1-chloro-2,3-epoxypropane, its O-epoxypropyl-, O-ethyl-, and O-benzylderivatives are described. Novel hydrazone derivatives with pyrazolidine units were also synthesized. The compounds were characterized by spectroscopic methods as well as elemental analyses.     

Synthesis of 1,2-Diphenylpyrazolidin-4-ol and its Derivatives

Summary. A synthesis of 1,2-diphenylpyrazolidin-4-ol via direct heterocyclization of 1,2-diphenylhydrazine with 1-chloro-2,3-epoxypropane, its O-epoxypropyl-, O-ethyl-, and O-benzylderivatives are described. Novel hydrazone derivatives with pyrazolidine units were also synthesized. The compounds were characterized by spectroscopic methods as well as elemental analyses.     

Efficient asymmetric selenocyclizations of alkenyl oximes into cyclic nitrones and 1,2-oxazines promoted by sulfur containing diselenides

Treatment of the di-2-[(1S)-1-(methylthio)ethyl]phenyl diselenide or of the di-2-methoxy-6-[(1S)-1-methylthio)ethyl]phenyl diselenide with bromine and silver triflate afforded the corresponding electrophilic selenylating triflates which were used in situ to promote the asymmetric selenocyclization of γ-alkenyl oximes and δ-phenyl-γ-alkenyl oximes. The course of these reactions and hence the structures of the cyclization products were dictated by the (E)- or (Z)-geometry of the starting oximes. The two types of cyclization products were either the cyclic nitrones or the 1,2-oxazines; in both cases the reactions proceeded with excellent yields, complete regioselectivity and good diastereoselectivity.     

Reaction of 1,2,4-triazole-3-thiones with 1-chloro-2,3-epoxypropane

Addition of 1-chloro-2,3-epoxypropane to 1,2,4-triazole-3-thiones depending on the ratio of the reactants leads to the formation of 3-(1-chloro-2-hydroxypropyl)-3-(1-chloro-2-hydroxypropylthio)-1,2,4-triazoles. 3-Hydroxy-1,2,4-triazolo[2,3-b] tetrahydro-1,3-triazines have been synthesized by intramolecular cyclization of the monoadducts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 271–274, February, 1987     

Benzofurans. Improved syntheses of bufuralol, 7-ethyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran,and 1″-oxobufuralol, 7-acetyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran

An improved laboratory scale synthesis of bufuralol ( 1 ) and 1″-oxobufuralol ( 4 ) was accomplished. The intermediate benzofurans were prepared via aromatization of 2,3-dihydrobenzofurans or by a one-step acidcatalyzed cyclization from 2,2-diethoxyethyl 4-bromo-6-ethyl-2-formylphenyl ether ( 23 ). Base-catalyzed cyclization of 3-(5-bromo-3-ethyl-2-hydroxyphenyl)-1.2-epoxypropane ( 16 ) provided the key intermediate, 5-bromo-7-ethyl-2-hydroxymethyl-2,3-dihydrobenzofuran ( 17 ). Selective functionalization of the C-2 and C-7 positions of the benzofuran ring system was accomplished to afford both 1 and 4 .     

Study of the Products from Reaction of 1(2)-Aminoanthraquinones with 1-Chloro-2,3-Epoxypropane

1(2)-(3-Chloro-2-hydroxypropylamino)anthraquinones were synthesized by the reaction of 1(2)-aminoanthraquinones with 1-chloro-2,3-epoxypropane and were then subjected to various transformations.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 505–516, April, 2005.     

Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives

High levels of stereocontrol are observed in the conjugate addition of lithium dibenzylamide to tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn), with addition occurring exclusively anti- to the 3-alkyl substituent. Treatment of a range of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (RS)-N-benzyl-N-[small alpha]-methylbenzylamide indicates that good enantiorecognition is observed (E > 80) in their mutual kinetic resolution. In these reactions, conjugate addition of the lithium amide occurs exclusively anti- to the 3-alkyl substituent, with subsequent C(1)-protonation occurring preferably anti- to the 2-amino group in the 3-Et, 3-Bn and 3-(i)Pr cases, giving predominantly the corresponding 1,2-syn-2,3-anti-diastereoisomers. Conjugate addition to (RS)-3-tert-butyl cyclopentene-1-carboxylate results in exclusive 2,3-anti -addition and a reversal in C(1)-protonation selectivity, giving predominantly the 1,2-anti-2,3-anti-diastereoisomer. Furthermore, the kinetic resolution of the tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds efficiently, giving, at between 47 and 51% conversion, the resolved 3-alkylcyclopentene-1-carboxylates in >85 to >98% ee and the beta-amino ester products of conjugate addition in high de, consistent with E > 80 in each case. Subsequent deprotection of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr) by hydrogenolysis and ester hydrolysis gives the corresponding 1,2-syn-2,3-anti-3-alkylcispentacins in >98% de and 98 +/- 1% ee. Selective epimerisation of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr, (t)Bu) by treatment with KO(t)Bu in (t)BuOH gives the corresponding 1,2-anti-2,3-anti-3-alkyl-beta-amino esters in quantitative yield and in >98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving the corresponding 1,2-anti-2,3-anti-3-alkylcispentacin hydrochlorides in >98% de.     

Glycosylidene Carbenes. Part 14. Glycosidation of partially protected galactopyranose-, glucopyranose-, and mannopyranose-derived vicinal diols

The relation between H-bonding in diequatorial trans-1,2 and axial, equatorial cis-1,2-diols and the regioselectivity of glycosidation by the diazirine 1 was examined. H-Bonds were assigned on the basis of FT-IR and ¹H-NMR spectra (Fig. 1). Glycosidation by 1 of the gluco-configurated diequatorial trans-2,3-diols 4–7 yielded the mono-glucosylated products 16/17/20/21 (69–89%); 1,2-/1,3-linked products (37–46:63–54), 24/25/28/29 (60–63%; 1,2-/1,3-linked products 46–51:54–49), 32–35 (69–94%; 1,2-/1,3-linked products 45–52:55–48), and 36/37/40/41 (59–63%; 1,2-/1,3-linked products 52–59:48–41), respectively (Scheme 1, Table 3). The disaccharides derived from 4, 5 , and 7 were characterized as their acetates 18/19/22/23, 26/27/30/31 , and 38/39/42/43 , respectively. Glycosidation of the galacto-configurated diequatorial 2,3-diols 8 and 9 and the manno-configurated diequatorial 3,4-diol 10 by 1 (Scheme 2, Table 3) also proceeded in fair yields to give the disaccharides 44–47 (69–80%;1,2-/1,3-linked products ca. 1:1), 48–51 (51–61%;1,2/-1,3-linked products 54–56:56–54), and 56/57/60/61 (71–80%; 1,3-/1,4-linked products 49–54:51–46), respectively. The 1,3-linked disaccharides 56/57 derived from the diol 10 were characterized as the acetates 58/59 . The regio- and stereoselectivities of the glycosidation by 1 were much better for the α-D -manno-configurated axial, equatorial cis-2,3-diol 11 and the galacto-configurated axial, equatorial cis-3,4-diol 13 (1,2-/1,3-linked disaccharides ca. 3:7 for 11 and 1,3-/1,4-linked disaccharides ca. 4:1 for 13 ; Scheme 3, Table 4). The regio- and stereoselectivity for the β-D -manno-configurated cis-2,3-diol 12 were, however, rather poor (1,2-/1,3-linked products 48:52). The 1,2-linked disaccharides 66/67 derived from 12 were characterized as the acetates 70/71 . Koenigs-Knorr-type glycosidation of the cis-diols 11–13 by 2 or 3 proceeded with a similar regio- and a higher stereoselectivity (α-D > β-D with the donor 2 and α-D < β-D with the donor 3 ) than with 1 , with the exception of 12 which did not react with 2 . The regioselectivity of the glycosidations by 1 agrees fully with the H-bonding scheme of the diols and with the hypothesis that the intermediate carbene is preferentially protonated by the most weakly H-bonded OH group. The regioselectivity of the glycosidation by 2 and by 3 is determined by a higher reactivity of the equatorial OH groups and by H-bonding. Several H-bonded and equilibrating isomers of a given diol may intervene in the glycosidation by 1 , or by 2 and 3 , resulting in the same regioselectivity. The low nucleophilicity of 12 and the low degree of regioselectivity in its reaction with 3 show that stereoelectronic effects may also profoundly influence the nucleophilicity of OH groups.     

Reaction of o-diaminoanthraquinones with malonic ester

The reaction of 1,2- and 2,3-diaminoanthraquinones with malonic ester was studied. It was established that the reaction products are N-ethoxymalonyl-o-diaminoanthraquinones and their heterocyclic derivatives — 1H-2-ethoxycarbonylmethylanthraimidazolediones. N-Ethoxymalonlyl-2,3-anthraquinone undergoes cyclization to 1H-2,3,4,5-tetrahydroanthra(2,3-b]-1,4-diazepine-2,4,7,12-tetraone when it is heated with sodium methoxide in absolute methanol, whereas 2-N-ethoxymalonyl-1,2-diaminoanthraquinone undergoes cyclization to 1H-2-ethoxy carbonylmethy lanthra-1,2-d]imidazole-6,11-dione.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 965–968, July, 1978.     

Condensed imidazo-1,24-azines. 28. Synthesis and transformations of 2-aroylmethyl-6,7.-diphenylimidazo-[1,2-b]-1,2,4-triazin-4H-3-ones

The reaction of 1,2-diamino-4,5-diphenylimidazole with 3-aroyl-2-propanonoic acid yields 2-aroylmethyl-6,7-diphenylimidazo[1,2-b]-1,2-4-triazin-4H-3-one. The cyclization pathways of these imidazoriazines leading to condensed furo[2,3-e]-, thieno[2,3-e]-, pyrrolo[2,3-e]-, and furo[3,2-e]limidazo[1,2,-b]-1,2,4-triazines were studied. A mass spectrometric study was carried out on the decomposition of these products upon electron impact. For Communication 27, see [1]. Kherson Industrial Institute, 325008 Kherson, Ukraine. A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 117071 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 258–262, February, 1998.     

Synthesis of unsaturated organoselenium compounds via the reaction of organic diselenides with 2,3-dichloro-1-propene in the hydrazine hydrate-KOH system

Dimethyldiselenide reacts with 2,3-dichloro-1-propene at 20–25°C in the hydrazine hydrate-KOH medium to form 2-chloro-3-methylselanyl-1-propene with 90% yield. Diphenyldiselenide in the reaction with 2,3-dichloro-1-propene, depending on the conditions, can give quite selectively four products: 2-chloro-3-phenylselanyl-1-propene, phenylselanylpropadiene, 1-phenylselanyl-1-propyne, and Z-1,2-bis(phenylselanyl)-1-propene. The effect of the selenium atom on the reaction direction and the products structure is discussed.     

Interaction of 2-(R-amino)-benzothiazoles with 3-furfuryloxy-1,2-epoxypropane

3-Furfuryloxy-1,2-epoxypropane reacts with 2-aminobenzothiazole at the endo- and exocyclic nitrogen atoms but its R-amino derivatives — only at the nitrogen atom of the thiazole ring. Compounds isomeric with the obtained products were prepared by interaction of the same oxirane with 2-imino-3-methylbenzothiazolines and also with methylamine with subsequent treatment with 2-chlorobenzothiazole.Institute for the Chemistry of Plant Materials, Uzbekistan Academy of Sciences, Tashkent 700170. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 85–89, January, 2000.     

Stereochemistry and mechanism of the hydrogenation of substituted cyclopentenes

1,2- and 2,3-disubstituted cyclopentenes were hydrogenated with several transition metal catalysts. The hydrogenation of 1,2-disubstituted cyclopentenes gave preferably the cis products with Raney Ni, whereas 2,3-disubstituted cyclopentenes gave preferably the trans isomers. The trans products were favoured in the hydrogenation of 1,2- and 2,3-dialkylcyclopentenes with Pt or Pd catalysts. A detailed product analysis of the hydrogenation of 1,2-dialkylcyclopentenes indicates that the double bond migration occurred to form 2,3-dialkylcyclopentenes in advance of the hydrogenation. In contrast, 1-methyl-2-phenylcyclopentene gave predominantly the cis product irrespective of the kind of catalyst. These results suggest the formation of a π-benzylic species during the course of the reaction. The mechanism is discussed in terms of the modified Horiuti-Polanyi mechanism.     

Ionic telomerization of 1-chloro-2,3-epoxypropane with allyl alcohol and properties of products obtained

Ionic telomerization of 1-chloro-2,3-epoxypropane with allyl alcohol in the presence of boron trifluoride etherate as a route to halogenated epoxy oligoethers was studied. Selective chlorination or bromination of the intermediate oligo(chlorohydrin), followed by dehydrochlorination (epoxidation) of the intermediate oligohalohydrins with NaOH, was performed. The synthesized products are effi cient as active diluents for a compound based on ED-20 resin.