Nucleoside H-phosphonates. 12. Synthesis of nucleoside 3'-(hydrogen phosphonothioate) monoesters via phosphinate intermediates

Thio Effects on the Departure of the 3′‐Linked Ribonucleoside from Diribonucleoside 3′,3′‐Phosphorodithioate Diesters and Triribonucleoside 3′,3′,5′‐Phosphoromonothioate Triesters: Implications for Ribozyme Catalysis

“…At pH < 4, 21 was not any more accumulated, but 2 a and 2 b were converted to a mixture of 2',3'-(23 a,b), 3',3'-(24 a,b), and 2',2'-phosphorothioate diesters (25), probably via a 2',3'-cyclic phosphoro-A C H T U N G T R E N N U N G monothioate triester (not accumulated). Consistent with previous studies, [11] the latter intermediate underwent only endocyclic fission to acyclic phosphoromonothioate diesters (23)(24)(25) at pH > 4. On going to more acidic solutions, exocyclic fission of the 2',3'-cyclic phosphoroA C H T U N G T R E N N U N G monothioate triester to 2',3'-cyclic phosphoromonothioate (26 a), however, started to compete and these reactions became significant side reactions at pH < 2.…”

“…Bis(uridin-3'-yl) phosphorodithioate (2 a) and 2',5'-di-Omethyluridin-3'-yl uridin-3'-yl phosphorodithioate (2 b) were synthesized by the hydrogen phosphonate methodology described by Stawinski et al [24] (Scheme 3). Accordingly, 2',5'-bis-O-(tert-butyldimethylsilyl)uridine 3'-hydrogenphosphonothioate (10) prepared from 2',5'-bis-O-(tert-butyldimethylsilyl)uridine (9) was allowed to react with this nucleoside or 2',5'-di-O-methyluridine (6) in the presence of diphenylphosphorochloridate and the product was oxidized with elemental sulfur to obtain 11 a,b.…”

Recent advances in phosphorus–carbon bond formation: synthesis of H-phosphinic acid derivatives from hypophosphorous compounds

“…In fact, stock solutions of EtOP(O)H 2 in CH 3 CN, THF, or toluene, were found to be stable at room temperature under nitrogen for over a month (less than 10% decomposition). Alkyl phosphinates for which the corresponding alkoxysilane is not commercially available can be prepared by transesterification of PhOP(O)H 2 , or by a slightly modified Stawinski approach [10], using anilinium hypophosphite (AHP), PivCl, pyridine, and an alcohol (Eqs. (3) and (4), respectively).…”

The Chemical Synthesis of Bioactive Glycosylphosphatidylinositols from Trypanosoma cruzi Containing an Unsaturated Fatty Acid in the Lipid

“…It was then a subject of successive reduction of the azido groups with Ph 3 P, N protection with Boc anhydride (!37), and selective cleavage of the primary TBS ether with 3HF·Et 3 N, thus cleanly producing the 6''''hydroxy glycan-inositol-phosphonate compound 38 (80 %). Furthermore, the introduction of the ethanolamine phosphate moiety was performed by the condensation of 38 with the hydrogenphosphonate derivative 4 (activated by pivaloyl chloride) [23] followed by in situ oxidation with iodine in aqueous pyridine. The phosphonate-phosphate block 39 was isolated in 88 % yield prior to the final desilylation with TBAF/AcOH (at 55 8C), which gave the 1-hydroxy glycoconjugated derivative 40.…”