Synthesis of nucleoside 3′,5′-cyclic boranophosphorothioate, a new type of cyclic nucleotide

Abstract

The first examples of a borane-containing doubly P-modified chiral cyclic nucleoside monophosphate (cNMP), e.g., thymidine and 5-fluoro-2'-deoxyuridine 3',5'-cyclic boranophosphorothioates, have been synthesized; these cNMP analogues with increased lipophilicity could be potential anticancer prodrugs and useful probes for mechanistic studies.

Synthesis of Acyclothymidine Triphosphate and α-P-Boranotriphosphate and Their Substrate Properties with Retroviral Reverse Transcriptase

“…Alternatively, an in situ boronation of cyclotriphosphite 3 resulted in P 1 -acyclothymidinyl- P 1 -borano- P 2 , P 3 -dioxo-cyclotriphosphate 4 . The presence of the P → B bond in cycloboranophosphate 4 was confirmed by 31 P NMR spectra, which showed a broad peak centered at δ 90.30 for P 1 , characteristic of a boranophosphate group. 5a, A slight upfield shift of the doublet at δ 24.47 ( J = 45.82 Hz) for P 2 and P 3 peaks in cyclic compound 4 was also observed. ,8a-c Of several borane complexes tried for boronation, a 2 M solution of borane-dimethyl sulfide in THF gave the best results. Cycloboranophosphate 4 was finally treated with water/triethylamine to give the ring-opened product acycloTTP-α-BH 3 5b .…”

“…Formation of a triphosphate usually requires the use of a phosphitylating reagent. Salicyl phosphochloridite, which has been used extensively in the synthesis of NTP and NTP-α-BH 3 , 8a-c is difficult to handle because of its high reactivity and hygroscopicity. As an alternate phosphitylating reagent, we chose a reasonably reactive phosphorus compound, bis(diisopropylamino)chlorophosphine ([( i Pr) 2 N] 2 PCl).…”

The Preparation, Structural Characteristics, and Physical Chemical Properties of Metal-Nitrosyl Complexes

“…Since then, many new structures have been synthesized that range from simple derivatives of triphenyl phosphine [20, 21] to more complicated structures that make use of different metal centers [22–24]. We choose to use the following examples to illustrate the structures, spectroscopic properties, and mechanisms of reactions.…”

“…The substitution of the CO group by TCNE is further accomplished by treating a 1:1 molar ratio of Fe(NO) 2 (CO)(PR 3 ) with TCNE, which afforded complexes of Fe(NO) 2 [PR 3 ](η 2 -TCNE) (where PR 3 = PPh 3 , 1 , P(OCH 3 ) 3 , 2 , P( n -Bu) 3 , 3 , PMe 2 Ph, 4 , and PEt 2 Ph, 5 ) [20]. These reactions typically occur over 1–2 h at room temperature with yields over 80%.…”

“…Thus, the radical anion, [Fe(NO) 2 PR 3 (η 2 -TCNE)] − , decomposes rapidly to yield a decomposition product. The complexes 2–5 ( E pc = −0.990 V ~ −1.146 V) are harder to reduce than the free TCNE ligand ( E 1/2 = −0.207 V) but are easier to reduce than the corresponding carbonyl compound, Fe(NO) 2 (PR 3 )(CO) ( E ° = −1.96 ~ −2.15 V) [20]. The coordination of TCNE leads to a shift in the reduction potentials to a more negative value compared to free TCNE and to a more positive value in comparison with Fe(NO) 2 (PR 3 )(CO).…”