An efficient method for the synthesis of selenium modified nucleosides: its application in the synthesis of Se-adenosyl-l-selenomethionine (SeAM)

Abstract

In this paper, we report that a versatile method for the synthesis of 5'-selenium modified nucleosides has been explored on the basis of a 2-(trimethylsilyl)ethyl (TSE) selenyl group as a selenating donor. We demonstrate the broad utility of this method through direct introduction of various functional groups into 5'-TSE-selenonucleosides. This original method offers additional advantages for the preparation of these compounds, such as high functional group tolerance, ready availability of various electrophilic reagents, mild conditions, simple operation, and good yields. The utility of this approach is further demonstrated by the synthesis of Se-adenosyl-L-selenomethionine (SeAM) as a chemical reporter for methyltransferases.

Selenium‐NMR Spectroscopy in Organic Synthesis: From Structural Characterization Toward New Investigations

“…For example, Koketsu and co‐workers have reported an efficient synthetic method to prepare selenium modified nucleosides [111] . In this reaction, the 2‐(trimethylsilyl)ethyl seleno group was employed as the selenium source, promoting highly functional tolerance, mild conditions, and good yields of the expected products (Scheme 17).…”

“…For example, Koketsu and co-workers have reported an efficient synthetic method to prepare selenium modified nucleosides. [111] In this reaction, the 2-(trimethylsilyl)ethyl seleno group was employed as the selenium source, promoting highly functional tolerance, mild conditions, and good yields of the expected products (Scheme 17). The silyl group bonded to the selenium atom was removed with TBAF in DMF as the solvent at room temperature, followed by nucleophilic attack of the generated selenolate anion to an electrophilic species.…”

Voyage of selenium from environment to life: Beneficial or toxic?

“…Acts as a direct precursor of methylselenol, the key metabolite responsible for selenium's anticancer activity [213] Se-DL-cystine C 6 H 12 N 2 O 4 Se 2 May acts as an antioxidant or pro-oxidant depending on cellular conditions. It displays GPx-like activity under reducing conditions [214] Selenocystamine C 4 H 12 N 2 Se 2 Organic source for Se, which enhances apoptosis and DNA oxidation [170] Se-adenosyl-Lselenomethion-ine C 15 H 23 N 6 O 5 Se + Synthetic organo-Se compound that is used as a chemical reporter for methyltransferases [215,216] Selenium nanoparticles Se 0 Synthetic inorganic Se particles show lower toxicity in vivo and also have antibacterial/anticancer activities [217] Selenophene C 4 H 4 Se Considered to be a 'building block', molecule as functional groups can be added to the main ring structure. This addition can change the toxicity of selenophene, making it highly variable and customizable Selenofurano-side C 13 H 23 O 4 Se Ameliorates memory deficit/loss in Alzheimer-like sporadic dementia [221] (Continues)…”

Preparation of 2′-Alkylselenouridine Derivatives via a 2-(Trimethyl­silyl)ethylselenation Approach

“…to attack to the C2′ position of 2,2′-O-cyclouridine, resulting in introduction of TSE selenyl moiety onto ribose in uridine skeleton. The second step involves Se-alkylation using high affinity of Si to F. TSE diselenide (1) was prepared according to our procedure as reported previously; 17 following treatment of elemental selenium with sodium borohydride (NaBH 4 ), alkylation of the activated selenium with 2-(bromoethyl)trimethyl silane provided the desired selenating reagent 1 in 71% yield. Since 2,2′-O-cyclouridine (2) has a primary alcohol at the C5′ position, 4,4′-dimethoxytrityl (DMT) protection was initially conducted.…”

“…The replacement of an oxygen atom by homologous sulfur and selenium atoms affects the chemical properties and often leads to useful alterations of its efficacy. Within the scope of our ongoing program aimed at the synthetic study of selenium-containing nucleosides, 17,18 we herein describe the strategy for the synthesis of 2′-alkylselenouridine derivatives.…”