Alkylating nucleosides. 1. Synthesis and cytostatic activity of N-glycosyl(halomethyl)-1,2,3-triazoles. A new type of alkylating agent

Abstract

1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivatives by treatment with (C6H5)3P/CCl4, (C6H5O)3P/Br2, and (C6H5O)3P/I2, respectively. 1-Benzyl-4-(fluoromethyl)-1,2,3-triazole was obtained from 1-benzyl-4-(bromomethyl)-1,2,3-triazole by treatment with KF and 18-crown-6. Chloromethyl-, bromomethyl-, and iodomethyl-1,2,3-triazole derivatives inhibited the "in vitro" growth of HeLa cells. Some of these compounds increased the life span of mice bearing tumors.

N‐ and C‐acyclic thionuleoside analogues of 1,2,3‐triazole

“…The triplets (J 6.0 Hz) at δ 3.89, 3.75, and 3.91 were assigned to CH 2 -4 , respectively. The two doublets at the region 4.01-4.67 were identified as CH 2 -OH groups at C-4 and C-5 of the triazole ring, which concluded from comparison to the alcohol analogues prepared by de la Heras et al [25], while the hydroxyl groups were identified by D 2 O exchange. The mesylate groups of 9 appeared as two singlets at δ 3.12 and 3.01.…”

“…In connection with our synthetic approaches on the synthesis of acyclic N-and C-nucleosides [17][18][19][20] and the 1,2,3-triazoles [21] and their carbamate analogues [22], we herein report on the synthesis of novel acyclic 1,2,3-triazole Nthionucleoside analogues bearing 1,2,3-triazole ring carrying potential halomethyl and carbamate groups in addition to their rearrangement to the C-thio acyclic analogues via the sulfur participation, as promising antiviral or antineoplastic agents. A few halomethyl nucleoside derivatives have been described with potential cytostatic activity [23,24], such as N-glycosyl(halomethyl)-1,2,3-triazoles [25] and 3-substituted-thymidine analogues [26] as alkylating and antiviral agents, respectively.…”

Copper catalyzed 1,3-dipolar cycloaddition reaction of azides with N-(2-trifluoroacetylaryl)propargylamines

“…The well established approach utilized thus far for the synthesis of the [1,2,3]-triazole ring system relies on the thermal 1,3-dipolar Huisgen cycloaddition between alkynes 1 and azides 2 (Scheme 1) [2].…”

Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors

“…Based on these findings, we decided to introduce a new type of N2 substituents and evaluate the ability of obtained monophosphate analogs to inhibit the cap-dependent translation. We have chosen triazole-based groups as they not only exhibit excellent biological properties in the context of medicinal chemistry (Tron et al 2008;Hein and Fokin 2010) but are also stable to oxidation and reduction and resistant to metabolic degradation (De las Heras et al 1979). In this report, we describe the synthetic route for the preparation of N2-triazole-containing 7-methylguanosine-5 ′ -monophosphates (mononucleotide cap analogs), and their biological evaluation as effective inhibitors of a cap-dependent translation.…”