2-Fluoropurine ribonucleosides

Hewson, Kathleen

doi:10.1021/jm00297a022

Cited by 16 publications

(15 citation statements)

References 6 publications

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“…14, respectively, were particularly sensitive to bases in protic media, ~~ndoubtedly due to abstraction of the malonic ester proton and subsequent transformations. A similar observation was encountered in the attempted deacetylation of diethyl 2-(2,3,4,6-tetra-0-acetyl-P-D-glucopyranosyl) malonate (I 7) and in the debenzoylation of l-cyano-2,3,5-tri-0-benzoyl-~-~-ribof~1ranose (12,31). Whereas the reaction of the bromide 2 with sodio diethyl malonates in 1,2-dimethoxyethane led to ketals almost exclusively, the analogous reaction with sodio triethyl 1,1,2-ethanetricarboxylate led to appreciable C-C condensation at the anomeric carbon atom.…”

Section: Discussionsupporting

confidence: 57%

Carbanions in Carbohydrate Chemistry: Approaches to Chemical Precursors of C-Nucleosides

Hanessian¹,

Pernet²

1974

Can. J. Chem.

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The condensation of D-ribofuranosyl halides containing participating (benzoate) and nonparticipating (benzyl) substituents, with sodio dialkyl malonates and sodio triethyl 1,1,2-ethanetricarboxylate is described. In the presence of participating groups at C-2, the major and sometimes exclusive products were the 1,2-ketal derivatives. Both a-and a-anomeric D-ribofuranosyl malonates were formed in the non-participating series. The possibility of epimerization (anomerization) was experimentally demonstrated.Similar results were obtained with the more highly functionalized tricarbethoxy carbanion. For the participating series however, 20% of C-glycoside was obtained. Condensations with sodio diethyl malonate were also done in the D-arabino series (0-benzyl protecting group) and the anomeric C-glycosyl compounds were isolated and characterized. The mechanistic aspects of these condensations are discussed.La condensation des halogCnures de D-ribofurannosyle contenant des groupes participant (benzoate) et non-participant (benzyle) avec les sels de sodium des malonates de dialkyle et de I'tthane tricarboxylate-1,1,2 de triethyle est dCcrite. En presence d e groupes participants en position-2, les produits majoritaires et dans certains cas uniques furent les acCtals-1,2. Les deux anomtres a-et a-ribofurannosyle malonates furent formts lorsque I'on a utilist les groupes non-participants. La possibilite d'une epimerisation (anomtrisation) a ete demontree expCrimentalement.Des rksultats semblables ont CtC obtenus avec les carbanions tricarbethoxy les plus substituees; cependant, dans le cas de groupes participants on a obtenu 20% de C-glycoside. On decrit tgalement les condensations du malonate de diethyle sod6 dans la serie D-arabitro (le substituant 0-benzyle Ctant utilise comme groupe protecteur) et les composes anomtres Cglycosyles furent isoles et caractkrists. Les aspects mecanistiques d e ces condensations sont discutts.

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Section: Discussionsupporting

confidence: 57%

Carbanions in Carbohydrate Chemistry: Approaches to Chemical Precursors of C-Nucleosides

Hanessian¹,

Pernet²

1974

Can. J. Chem.

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“…Its mode of action involves incorporation into the 3'-end of an RNA molecule and this prevents further elongation, thereby acting as a chain terminator (Suhadolnik, 1979). A major problem associated with the clinical use of these nucleoside antitumour antibiotics is that the enzyme adenosine deaminase (ADAase) (Montgomery, 1970) causes deamination of purine antimetabolites and hence limits their activity. The aim of the structural studies detailed in this paper is to examine compounds potentially active in chain termination of RNA that are, at the same time, resistant to ADAase, although without being an inhibitor (Montgomery, Thomas, Zell, Einspahr & Bugg, 1985), which causes other toxic effects produced by excess adenosine (Plagemann & Wohlhueter, 1981).…”

mentioning

confidence: 99%

A structural study of 3'-deoxytubercidin and 3-deaza-3'-deoxyadenosine

McKenna¹,

Kuroda²,

Neidle³

et al. 1987

Acta Crystallogr C

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“…For example, a key compound in the biosynthesis of natural purine components of RNA and DNA is the ribotide 4(5)-aminoimidazol-5(4)-carboxamide [1,2]. Involvement of 4,5-aminoimidazolcarboxamide in metabolic processes can be used to synthesize its antimetabolites that can inhibit biosynthesis after biotransformations and thereby suppress tumor growth.…”

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confidence: 99%

Imidazole derivatives and their antitumor activity (review)

Iradyan

Arsenyan

et al. 2009

Pharm Chem J

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Bis(2-chloroethyl)amino derivatives of imidazole, 4(5)-aminoimidazol-5(4)-carboxamide, 4-nitro-5-thioimidazole, benzimidazole, and imidazolylpeptides are reviewed. Data are presented for active compounds, some of which have passed the preclinical testing stage. Structures under consideration are interesting with respect to both the search for new antitumor drugs and the synthesis of compounds with different biological properties.Key words: imidazole, 4(5)-aminoimidazol-5(4)-carboxamide, 4-nitro-5-thioimidazole, benzimidazole, imidazolylpeptides, bis(2-chloroethyl)amino derivatives, antitumor activity.Chemotherapy of tumors is one of the most important medical achievements of the 20th century. Chemotherapy of malignant neoplasms was identified as an independent area of oncology in the middle of the 1940s with the advent of alkylating agents.It is currently possible to treat patients with Burkitt's lymphoma, Hodgkin's disease, chorionepithelioma, germinogenic ovarian diseases, Ewing's sarcoma, Kaposi's sarcoma, osteosarcoma, breast and prostate cancer, and certain acute forms of leukemia and lymphosarcoma. However, any treatment method is ineffective at advanced stages of the disease in all instances.The ability to treat cancers with derivatives of bis(2-chloroethyl)amine was discovered serendipitously. The doctor on-board the transport ship John Harvey that was carrying mustard gas (1943) noticed the toxic effect of this compound on the blood of sailors. These and other observations signaled the beginning of studies on the effect of mustard gas and its derivatives on experimental and human tumors. Mustard gas itself is highly toxic and is not used in medical practice. A methyl analog of mustard gas, embichin, which was also one of the first antitumor preparations, was proposed in 1946 as a therapeutic. Searches in the next 20 -30 years in this direction discovered derivatives of bis(2-chloroethyl)-amine with aromatics such as novembichin, chlorambucil, paphencyl; with amino-acids, sarcolysine, asaline, lofenal; with hemi-alcohols, degranol; with phosphorylated amines, cyclophosphane; and with nitrogen-containing heterocycles, dopan and fluorodopan.A distinguishing feature of these preparations is the rather effective action on malignant systemic diseases of blood and hematopoietic organs.The presence of imidazole derivatives in man and their involvement in metabolism has drawn the attention of researchers. For example, a key compound in the biosynthesis of natural purine components of RNA and DNA is the ribotide 4(5)-aminoimidazol-5(4)-carboxamide [1,2]. Involvement of 4,5-aminoimidazolcarboxamide in metabolic processes can be used to synthesize its antimetabolites that can inhibit biosynthesis after biotransformations and thereby suppress tumor growth.The biological activity of bis(2-chloroethyl)amines is due to their interaction with carboxylic, sulfhydryl, and amino groups of proteins. They react with nucleic acids at the phosphoric-acid hydroxyls and DNA guanine at the 7-nitrogen atom [3].A characteristic of 2...

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2-Fluoropurine ribonucleosides

Cited by 16 publications

References 6 publications

Carbanions in Carbohydrate Chemistry: Approaches to Chemical Precursors of C-Nucleosides

Carbanions in Carbohydrate Chemistry: Approaches to Chemical Precursors of C-Nucleosides

A structural study of 3'-deoxytubercidin and 3-deaza-3'-deoxyadenosine

Imidazole derivatives and their antitumor activity (review)

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