58944-73-3

Usage

Uses

Used in Biochemical Research:
Sinefungin is utilized as a bioprobe to block methyltransferase-dependent pathways, providing valuable insights into the role of these enzymes in various biological processes.
Used in Antimicrobial Applications:
Sinefungin is used as an antifungal agent with broad biological activity, isolated from Streptomyces species. It inhibits the methylation of bases in DNA and RNA, which in turn alters cytosine deamination and gene expression, contributing to its antimicrobial properties.
Used in Drug Development:
Sinefungin's derivatives can be employed as inhibitors and structure probes for human protein lysine methyltransferase SETD2, aiding in the development of new therapeutic agents targeting this enzyme.
Used in Microbiology:
Sinefungin is used to inhibit biofilm growth in Streptococcus pneumoniae, offering potential applications in controlling bacterial infections and understanding the mechanisms of biofilm formation.

Biochem/physiol Actions

Probable transcription factor. Plays a critical role in the control of immune response.

References

1) Barbes?et al. (1990),?Effects of sinefungin and S-adenosylhomocysteine on DNA and protein methyltransferases from Streptomyces and other bacteria;? FEMS Microbiol. Lett.,?57?239 2) Yebra?et al. (1991),?The effect of sinefungin and synthetic analogues on RNA and DNA methyltransferases from Streptomyces;? J. Antibiot. (Tokyo),?44?1141 3) Cheng?et al. (2004),?Small molecule regulators of protein arginine methyltransferases;? J. Biol. Chem.,?279?23892 4) Schluckebier?et al. (1997), Differential binding of S-adenosylmethionine S-adenosylhomocysteine and Sinefungin to adenine-specific DNA methyltransferase M. TaqI;? J. Mol. Biol., 265?56 5) Yadav?et al. (2014),?Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits Streptococcus pneumonia biofilm growth;? Biomed. Res. Int.,?2014?156987

InChI:InChI=1/C15H23N7O5/c16-6(1-2-7(17)15(25)26)3-8-10(23)11(24)14(27-8)22-5-21-9-12(18)19-4-20-13(9)22/h4-8,10-11,14,23-24H,1-3,16-17H2,(H,25,26)(H2,18,19,20)

Upstream product

• 135056-73-4 (2S,5S)-6-[(3aR,4R,6R,6aR)-6-(6-Benzoylamino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-2-benzyloxycarbonylamino-5-tert-butoxycarbonylamino-hexanoic acid benzyl ester 
• 180776-45-8 (2S,5S)-2-Amino-6-[(2R,3S,4R,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-5-(benzyl-benzyloxycarbonyl-amino)-hexanoic acid 
• 50466-88-1 1-(6-benzoylamino-purin-9-yl)-6-diethoxyphosphoryl-O²,O³-isopropylidene-1,5,6-trideoxy-heptofuranurononitrile 
• 33985-40-9 (3aR,4S,6R,6aR)-tetrahydro-6-methoxy-2,2-dimethylfuro-[3,4-d][1,3]dioxole-4-carbaldehyde 
• 110414-90-9 α-N-tosyl-δ-N-carbobenzoxyornthine 
• 124288-73-9 1,1-dimethylethyl (S)-2-<<(4-methylphenyl)sulfonyl>-amino>-5-<<(phenylmethoxy)carbonyl>amino>pentanoate 
• 124289-01-6 1,1-dimethylethyl 6(S)-azido-5,6,7,8,9-pentadeoxy-9(S)-<<(4-methylphenyl)sulfonyl>amino>-1,2,3-tri-O-acetyl-β-D-ribo-decofuranuronate 
• 124288-83-1 1,1-dimethylethyl -9(S)-<<(4-methylphenyl)sulfonyl>amino>-2,3-O-(1-methylethylidene)-β-D-allo-decofuranosid>uronate 
• 124288-90-0 1,1-dimethylethyl 1-(6-amino-9H-purin-9yl)-6(S)-azido-2,3-di-O-acetyl-1,5,6,7,8,9-hexadeoxy-9(S)-<<(4-methylphenyl)sulfonyl>amino>-β-D-ribo-decofuranuronate 
• 124288-91-1 1,1-dimethylethyl 1-(6-amino-9H-purin-9yl)-6(S)-azido-1,5,6,7,8,9-hexadeoxy-9(S)-<<(4-methylphenyl)sulfonyl>amino>-β-D-ribo-decofuranuronate 
• 124288-92-2 (2S,5S)-5-Amino-6-[(2R,3S,4R,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-2-(toluene-4-sulfonylamino)-hexanoic acid tert-butyl ester 
• 124288-76-2 (S)-6-Hydroxy-6-((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-5-nitro-2-(toluene-4-sulfonylamino)-hexanoic acid tert-butyl ester 
• 124288-85-3 1,1-dimethylethyl amino>-2,3-O-(1-methylethylidene)-β-D-ribo-decofuranosid>uronate 
• 124288-77-3 1,1-dimethylethyl amino>-2,3-O-(1-methyl-ethylidene)-β-D-ribo-dec-5-enofuranosid>uronates 

Relevant academic research and scientific papers

Synthesis of Sinefungin and Its C-6' Epimer

A synthesis of the nucleoside antibiotic sinefungin (1) and its C-6' epimer is described.It was accomplished by coupling a functionized adenosine derivative, 2, with an aldehyde synthon, 3, derived from L-amino acid to give the sinefungin precursor 4.The construction of the skeleton of the glycosyl moiety of sinefungin (1) could be achieved starting from methyl riboside.The adopted sequence was probed further by synthesizing the sinefungin analogue 9b (two C-6' epimers).This synthesis established that the Hoffmann rearrangement of both amides 8b took place with complete retention of configuration at C-6'.Finally, sinefungin derivatives 9c were obtained, and one of these found to be identical with the same derivative prepared from authentic sinefungin (1).It was easily converted to sinefungin (1).

Total synthesis of (+)-sinefungin

Sinefungin (1) a nucleoside antibiotic isolated from Streptomyces has been synthesized from D-ribose. Both the C-6 and C-9 stereogenic centers were constructed by efficient asymmetric syntheses. The C-6 amine stereochemistry was set by a highly diastereoselective allylation (> 99% de) of a (1S,2R)-1-amino-2-indanol-derived oxazolidinone 9 followed by a Curtius rearrangement of 11 to 12. The C-9 amino acid stereochemistry of sinefungin (1) was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an α-(acylamino)acrylate derivative. The anomeric adenosylation of the mixture of anomeric acetates 20 in the presence of C-6 urethane NH was found to be extremely difficult. Conversion of the C-6 urethane NH as its N-benzyl derivative 21 was necessary prior to the adenosylation reaction. Successful adenosylation was effectively carried out by Vorbruggen's protocol utilizing persilylated N6-benzoyladenine and trimethylsilyl triflate.

Expedient Synthesis of Natural (S)-Sinefungin and of its C-6' Epimer

Sinefungin 1a and 6-epi-sinefungin 1b have been prepared from adenosine and L-aspartic acid.The key step in the synthesis was the coupling of the radical derived from 14 with the unsaturated amide 13.The latter was obtained by a radical reaction from L-as

Stereoselective Synthesis and Absolute Stereochemistry of Sinefungin

Sinefungin has been synthesized from D-ribose, L-ornithine, and adenine.L-Ornithine was converted to its δ-nitro analogue 10, which was coupled to the ribose derived aldehyde 11 by a potassium fluoride catalyzed nitro-aldol reaction.The resulting nitro al