182007-86-9

Usage

Uses

Used in Biotechnology and Biomedical Research:
2'-O-(tert-Butyldimethylsilyl)-N-isobutyrylguanosine is used as a building block for the synthesis of modified RNA molecules, enabling the development of novel RNA-based therapeutics and diagnostic tools. The TBDMS group provides protection to the 2' hydroxyl group, allowing for selective deprotection and subsequent modification, while the isobutyryl group enhances solubility and facilitates mild condition removal for further functionalization.
Used in Nucleic Acid Research:
In the field of nucleic acid research, 2'-O-(tert-Butyldimethylsilyl)-N-isobutyrylguanosine serves as a key component in the synthesis of modified nucleic acids, contributing to the exploration of new chemical and structural properties of RNA and DNA. The chemical modification allows for the study of the effects of these modifications on nucleic acid stability, folding, and interactions with proteins and other biomolecules.
Used in Synthetic Chemistry:
2'-O-(tert-Butyldimethylsilyl)-N-isobutyrylguanosine is employed as a versatile intermediate in synthetic chemistry for the preparation of various guanosine derivatives with potential applications in medicinal chemistry and drug discovery. The TBDMS protection and isobutyryl acylation enable selective reactions and mild deprotection conditions, facilitating the synthesis of complex guanosine-based molecules with tailored properties.

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 81246-83-5 9-(5-O-dimethoxytrityl-β-D-ribofuranosyl)-2-N-isobutyrylguanine 
• 64350-24-9 N²-isobutyryl-2'-deoxyguanosine 
• 81279-39-2 N-(9-((2R,3R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-((tert-butyldimethylsilyl)oxy)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide 
• 401812-99-5 2'-O-(tert-butyldimethylsilyl)-3',5'-O-(di-tert-butylsilanediyl)guanosine 
• 118-00-3 G 
• 126628-29-3 2-amino-9-((4aR,6R,7R,7aS)-2,2-di-tert-butyl-7-hydroxytetrahydro-4H-furo[3,2-d][1,3,2]dioxasilin-6-yl)-1,9-dihydro-6H-purin-6-one 
• 401813-00-1 N-{9-[2,2-di-tert-butyl-7-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furo[3,2-d][1,3,2]dioxasilin-6-yl]-6-oxo-6,9-dihydro-1H-purin-2-yl}-isobutyramide 

Downstream Products

• 81279-39-2 N-(9-((2R,3R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-((tert-butyldimethylsilyl)oxy)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide 

Relevant academic research and scientific papers

ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria

A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5′-triphosphate-3′-diphosphate, and ppGpp: 5′-3′-bis-diphosphate), collectively called (p)ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p)ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p)ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2′-Deoxyguanosine-3′-5′-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site. As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents.

COMPOUNDS FOR TREATING BACTERIAL INFECTIONS

The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.

Synthesis of 2'-O-substituted ribonucleosides.

An efficient synthesis of 2'-O-substituted ribonucleosides, including 2'-O-TBDMS and 2'-O-TOM protected as well as 2'-O-Me and 2'-O-allyl derivatives is presented. Di-t-butylsilylene group was employed for simultaneous protection of 3'- and 5'- hydroxyl functions of nucleoside on the first step. Subsequent silylation or alkylation of free 2'-OH followed by introduction of suitable protection on the base moiety and removal of cyclic silyl protection gave target compounds in a high yield.

An efficient preparation of protected ribonucleosides for phosphoramidite RNA synthesis

An efficient synthesis of protected ribonucleosides useful for phosphoramidite RNA synthesis is described. Di-t-butylsilylene group was employed for simultaneous protection of 3′- and 5′-hydroxyl functions of nucleoside. Subsequent silylation of free 2′-O