ω,ω′-Appended nucleo-base derivatives of hypericin

ω,ω′-Disubstituted hypericin derivatives with the nucleo-bases thymine, cytosine, and adenine in these positions were prepared starting from tri-O-methyl-ω-bromoemodin. The most promising derivative proved to be that with a thymine moiety. It displayed the best solubility of the three products together with a potency to produce singlet oxygen and/or reactive oxygen species comparable to the parent compound hypericin. In addition, although no specific interaction with DNA or poly(2′-deoxyadenylic acid) could be detected, it proved to be significantly better accumulating in the nucleus of prostatic cancer LNCaP cells than hypericin making it a promising candidate for a second-generation photodynamic hypericin agent.     

ω,ω′-Urea- and -dithioacetal-derivatives of hypericin

An ω,ω′-disubstituted hypericin derivative bearing two dicyclohexylurea moieties separated by propionyl chains from the chromophore and an ω,ω′-dithioacetal of hypericin were prepared. Both showed excellent production of oxidizing species comparable to hypericin when irradiated with appropriate light as shown by the photodestruction of bilirubin IXα.     

ω,ω′-Urea- and -dithioacetal-derivatives of hypericin

An ω,ω′-disubstituted hypericin derivative bearing two dicyclohexylurea moieties separated by propionyl chains from the chromophore and an ω,ω′-dithioacetal of hypericin were prepared. Both showed excellent production of oxidizing species comparable to hypericin when irradiated with appropriate light as shown by the photodestruction of bilirubin IXα.     

α,ω-Bis-N-aziridinoalkanes

By reactions of ,-diamines with 1,2-dihaloethanes there were synthesized ,-bis-N-aziridinoalkanes (la-g) and bis-N-aziridinoethyl ether (II). From 1,3-diaminopropane and dichloroethane bis-aziridine (III) was isolated in addition to (Ia). NMR spectra of the products were studied.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 882–885, April, 1991.     

ω,ω′-imino dicarboxylic acids and some of their derivatives

Summary Starting from the corresponding-chloro carboxylic acids we prepared, -imino dicarboxylic acids and their N- and O- derivatives; the products had the following structures:     

Mono-Protected Diamines. N-tert-Butoxycarbonyl-α,ω-Alkanediamines from α,ω-Alkanediamines

We wish to report a convenient pathway to N-tert-butoxycarbonyl-α,ω-alkanediamines 2a-e [H₂N(CH₂)χNHBOC; χ=2, 3, 4, 5 and 6; (75–90% yields)] by treatment of the corresponding α,ω-alkanediamine with di-tert-butyl dicarbonate in dioxane as the solvent. Only small amounts of the bis-substituted N.N′-tert-butoxycarbonyl-α,ω-alkanediamines 3a-e were formed (2–9%) which were easily removed by an aqueous workup. The α,ω-alkane-aza-diamine 4 was also mono-protected (62% yield of 5) by the same methodology.     

New α,ω-diamido and α,ω-diamino mono-and bi-bridged acridine dimers

A novel set of dimers derived from 9-amino acridine was prepared and characterized by¹H and¹³CNMR. These derivatives are bridged at several different positions of the heterocyclic moieties, by the way of ,-diamido or ,-diamino side-chains. Additionally the preparation of some bi-bridged compounds was achieved.

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Neue ,-Dimaido- und ,-Diamino-Mono- und Bi-überbrückte Acridin-Dimere

Zusammenfassung Es wurde eine neue Reihe von Dimeren des 9-Aminoacridins hergestellt und mittels¹H und¹³C-NMR charakterisiert. Diese Derivate sind an verschiedenen Positionen des Heterocyclus mit ,-Diamido- oder ,-Diamino-Seitenketten überbrückt. Zusätzlich wurden auch einige zweifachüberbrückte Verbindungen hergestellt.

     

ω-三烷基及ω-吡啶翁基芳乙酮α氢核磁共振研究

用高分辨核磁共振研究了ω-三烷基铵基及ω-吡啶翁基芳乙酮α氢在D2O中的氘交换现象, 证实该类酮在酸性与中性条件下不产生烯醇化, 在弱碱性条件下则产生部分烯醇化。     

ω-氨基酸缩聚反应动力学研究

前曾报导9-氨基壬酸的缩聚,从开始到反应程度p增加到99％左右时止,均遵循二级反应。在这以后,由于体系粘稠的影响,迅速转为三级反应。本文报导在6-氨基己酸和11-氨基十一酸缩聚时,也出现同样现象,即在p逐渐到高于99％左右时,反应从二级转变为三级。可以说这一现象是AB型单体聚酰胺化的一般规律,从而澄清了文献中对这一问题的不同论点。     

SYNTHESE D'ACIDES ω-AMINO-ω-CARBOXY-ALKYLPHOSPHONIQUES

Abstract

La synthèse des acides ω-amino ω-carboxyalkylphosphoniques 1, a été réexaminée. Pour n = 4, 5 et 6, une synthèse générale, efficace et économique en 3 étapes est proposée: les acétamido (ω-bromoalkyl) malonates 12 sont préparés par transfert de phase à partir de l'acétamidomalonate de diéthyle et des dibromoalcanes commerciaux, puis condensés quantitativement sur le phosphite de triéthyle par une réaction d'Arbuzov. Une hydrolyse acide et une purification sur résine Dowex fournissent les aminoacides 1 (n = 4, 5, 6) avec un rendement global de l'ordre de 70%. L'acide amino-2 carboxy-2 éthylphosphonique 1 (n = 2) isolé de façon analogue avec un rendement de 70% est préparé par réaction de l'acétamidomalonate de diéthyle avec un halogéno-2 éthylphosphonate dans les conditions du transfert de phase liquide-solide.

ω-Amino ω-carboxyalkylphosphonic acids 1 synthesis is reviewed. For n = 4, 5, 6 a general, efficient and inexpensive synthesis is described; acetamido(ω-bromoalkyl)malonates 12 are prepared from commercial dibromoalkanes and acetamidomalonate using the phase transfer catalysis process, then condensed with triethylphosphite through an Arbuzov reaction. An acid hydrolysis followed by purification on Dowex gives aminophosphonic acids 1 (n=4, 5, 6) with a 70% overall yield. The lower acid 1 (n = 2) is obtained with an identical overall yield from acetamidomalonate and 2-haloethylphosphonate using also liquid-solid phase transfer catalysis.     

Electrochemical oxidation of tetramethyl esters of α,α,ω,ω-alcaneteracarboxylic acids

Cyclization of esters of butane-1,1,4,4- and pentane-1,1,5,5-tetracarboxylic acids during electrolysis in methanol in the presence of Nal produces, with a yield of 95%, the esters of cyclobutane-1,1,2,2- and cyclopentane-1,1,2,2-tetracarboxylic acids. Under similar conditions, esters of the highest ,,,-alkanetetracarboxylic acids undergo iodation and hydroxymethylation due to electrical oxidation of methanol to formaldehyde. During electrolysis in methanol in the presence of NaOAc, the esters of ,,,-alkanetetracarboxylic acids undergo effective hydroxymethylation, followed by cyclization into substituted five- and six-member lactones, or tetrahydrofurans when structurally possible.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2332–2339, October, 1992.     

ω-haloalkylphosphoryl compounds: Synthesis and properties

A general method of the synthesis of ω-haloalkylphosphoryl compounds was developed, a series of compounds of phosphonic and phosphine oxide type were synthesized. The ability of some ω-haloalkylphosphonates to undergo intramolecular cyclization into the corresponding 1,2-oxaphospholane and 1,2-oxaphosphorine was investigated depending on the solvent polarity, the presence of halogen ions in the solution, and temperature. Tetrahydrofuran was chosen as one of the most suitable solvents for the alkylation of CH acids with ω-haloalkylphosphoryl compounds.     

ω-Iodoalkyl(methyl)malonate Esters

Abstract

ω-Iodoalkyl(methyl)malonate esters have potential utility in the bioconjugate chemistry of steroids. A representative set of these esters with a variety of protecting groups and alkyl groups has been prepared. The compounds offer a range of elution values on silica, as well as several convenient deprotection options.

ω-Bromoalkyl(methyl)malonate esters are precursors of chalcogenobarbiturates, which, in radiolabeled form, may be useful as brain imaging agents.[1] Grigsby, R.A., Irgolic, K.J. and Knapp, F.F. 1983. Synthesis and spectral properties of diethyl organylchalcogenoalkyl(alkyl)malonates and 5-alkyl-5-(organylchalcogenoalkyl)barbiturates. J. Organomet. Chem., 259: 171–181.  [Google Scholar] Recently, we have become interested in the analogous ω-iodoalkyl(methyl)malonate esters because of their possible utility in the bioconjugate chemistry of steroids. It is known that steroids can be conjugated to platinum through a malonate moiety.[2] Gandolfi, O., Apfelbaum, H.C., Migron, Y. and Blum, J. 1989. Syntheses of cis-dichlorodiammineplatinum analogs having steroidal hormones bound to the metal atom via malonato bridges. Inorg. Chim. Acta, 161: 113–123.  [Google Scholar] Such platinated steroids are significant because of their potential as tissue-selective antitumor agents.     

Aminomethylation of (ω-alkylthioalkyl)phenols

The reactions of ()-alkylthioalkyl)phenols with formaldehyde and secondary amines afforded the corresponding aminomethyl derivatives, in which the dimethylamino group may be replaced by the alkylthio group.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1504–1507, June, 1996.