Stereoselectivity in the Synthesis of 3′-Deoxy-3′-C-(hydroxymethyl)uridines by Hydroboration and Conversion into a Building Block for Various 3′-Deoxy-3′-C-(methylene)uridine Analogues

Stereoselective Synthesis of Two New Trihydroxylated Pyrrolidines Using a Meyer–Schuster Rearrangement

“…The crude reaction mixture was treated with LiOH, to remove the TMS group and give a mixture (6:4) of diastereomeric hydroxy lactams 2 in 74% product 11 in an unsatisfactory yield of 32% (Scheme 4). However, when the alternative oxidant, NaBO 3 Á 4H 2 O, [8] was used, the yield of 11 was more satisfactory (50%). The configuration of 11 was established by NOESY NMR experiments (Fig.…”

Reactions of 3′-C-Halomethyl and 3′-C-Sulfonylmethyl Uridines with Phosphinic Acid Derivatives − Synthesis of Building Blocks for Oligonucleotides Containing 3′-C-Methylenephosphonate Linkages

“…[21,22] This and similar 3Ј-C-hydroxymethyl nucleosides had previously been converted into the corresponding halomethyl [8,15,16,22] and methanesulfonyl [21,22] derivatives for the synthesis of variously functionalised 3Ј-C-branched uridine analogues. We initially considered the previously reported mesylate derivative 2, and also the bromo and iodo derivatives 3 and 4, which were synthesized from hydroxymethyl derivative 1.…”

“…A solution of compound 1 [21,22] (400 mg, 0.620 mmol) in dry acetonitrile/ pyridine (95:5 v/v, 8 mL) under nitrogen was cooled to 0Ϫ2°C. Triphenylphosphane (228 mg, 0.87 mmol, 1.4 equiv.)…”

“…: Compound 1 [21,22] (230 mg, 0.357 mmol), Na 2 CO 3 (302 mg, 2.85 mmol, 8 equiv.) and tetra-n-butylammonium bromide (6 mg, 0.019 mmol, 0.05 equiv.)…”

An RNA modification with remarkable resistance to RNase A

“…15 After the latter appeared, it seemed likely that an analogous approach via alkylhydrogenphosphinates should be possible for incorporation of methylenephosphonate linkages into oligonucleotides. We have since developed synthetic methods for key steps towards ribonucleoside 3 0 -deoxy-3 0 -Cmethylenephosphinates, i.e., a 3 0 -carbon extension at the nucleoside level, 16 synthesis of methylenephosphinate building blocks 17 and oxidation of methylenephosphinate linkages 18 as well as evaluation of condensing agents for formation of the methylenephosphinate internucleoside linkage. 19 The potential biological use of methylenephosphonate RNA is dependent on its stability towards nucleases and phosphodiesterases.…”