S-Ribosylhomocysteine analogs containing a [4-thio]ribose ring.
The [4-thio]-S-ribosylhomocysteine (SRH) analogs containing substitution of a sulfur atom for the endocyclic oxygen were synthesized by coupling of the 4-thioribose substrates with a thiolate generated from the protected homocysteine. Coupling of the protected 1-deoxy-5-O-mesyl-S-oxo-4-thio-D-ribofuranose with homocysteinate salt gave the C4 epimers of [4-thio]-SRH at the sulfoxide oxidation level lacking a hydroxyl group at anomeric carbon. Treatment of these sulfoxides with BF3⋅Et2O/NaI affected simultaneous reduction to sulfide and global deprotection affording 1-deoxy-4-thio-SRH analog. Treatment of the protected 1-deoxy-S-oxo-4-thio-D-ribofuranose sulfoxide with DAST/SbCl3 resulted in the fluoro-Pummerer rearrangement to give 4-thio-β-D-ribofuranosyl fluoride. Mesylation of the latter at 5-hydroxyl position followed by coupling with homocysteinate salt and subsequent global deprotection with trifluoroacetic acid afforded [4-thio]-SRH thiohemiacetal.
Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
Adam J
AJ
Sobczak
Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA.
Christiane
C
Chbib
Department of Chemistry & Biochemistry, Florida International University, Miami, FL 33199, USA. Electronic address: wnuk@fiu.edu.
Stanislaw F
SF
Wnuk
D002244:Carbon / Q000737:chemistry; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D006711:Homocystine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D013455:Sulfur / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000737:chemistry
C487472:S-ribosyl-L-homocysteine; D006710:Homocysteine; D006711:Homocystine; D013455:Sulfur; D002244:Carbon; D014269:Trifluoroacetic Acid
Homocysteine; LuxS; S-Ribosylhomocysteine; Thioacetals; Thiosugars