Oxathiaphospholane approach to N- and O-phosphorothioylation of amino acids.
A method of highly efficient synthesis of N- and O-phosphorothioylated amino acids was developed. N- and O-(2-Thiono-1,3,2-oxathiaphospholanyl)amino acid methyl esters (3) were prepared in high yields in reaction of amino acid methyl esters with 2-chloro-1,3,2-oxathiaphospholane in pyridine in the presence of elemental sulfur. Compounds 3 were converted in high yield into the corresponding methyl or benzyl phosphorothioamides 6 and 7 by DBU-assisted treatment with methanol or benzyl alcohol. When 3-hydroxypropionitrile was used instead of methanol or benzyl alcohol, the corresponding 2-cyanoethylphosphorothioamidates 4 were obtained in high yield, from which the 2-cyanoethyl group was removed with concentrated ammonium hydroxide. The oxathiaphospholane methodology was also applied for the phosphorylation of amino acids. Thus, 2-oxo-1,3,2-oxathiaphospholane derivatives 10 were prepared by oxidation of compounds 3 with SeO(2.) Compounds 10 were transformed into the corresponding phosphate diesters or amidoesters upon treatment with 3-hydroxypropionitrile in the presence of DBU. The DBU-assisted oxathiaphospholane ring-opening process in 3 and 10 did not cause any measurable C-racemization of phosphorothioylated/phosphorylated amino acids.
Baraniak
Janina
J
Department of Bioorganic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland. baraniak@bio.cbmm.lodz.pl
Kaczmarek
Renata
R
Korczyński
Dariusz
D
Wasilewska
Ewa
E
D000596:Amino Acids / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D012266:Ribose / Q000031:analogs & derivatives* / Q000737:chemistry*; D013440:Sulfides
D000596:Amino Acids; D007202:Indicators and Reagents; D009711:Nucleotides; D010750:Phosphoproteins; D013440:Sulfides; C434797:oxathiaphospholane; D012266:Ribose