The stereochemistry at phosphorus of the SET-induced photorearrangement of diastereomeric 4-tert-butyl-2-phenylallyl-1,3,2-dioxaphosphorinanes (8) to the corresponding 2-phenylallylphosphonates (9), which involves exicted singlet 1,4-dicyanonaphthalene (1DCN*) as one-electron oxidant, was investigated. The rearrangement occurs with close to complete retention of configuration at phosphorus. The previously postulated mechanism for this photorearrangement is shown to be consistent with the stereochemical finding. Thus, one-electron reduction by DCN.- of the presumably stereospecifically formed distonic cyclic 1,3-cation radical intermediate 15, generated from cis-8 (Scheme 2), yields the thermodynamically stable diradical 16. beta scission of 16 forms phosphonate cis-9. An alternative mechanism involving beta scission of 15 to a styryl cation radical, prior to one-electron reduction to 15, is discounted on the basis of unpublished trapping studies using MeOH. The direct, kinetically controlled formation of diradical 16 rather than the thermodynamically less stable 21 with CH2 bonded apically to phosphorus is argued to be consistent with the essentially equal values of the quantum yield for phosphonate formation (phi P) on SET-induced rearrangement of the acyclic 2-phenylallyl phosphite 1 and phosphite 7 with phosphorus incorporated in a six-membered (1,3,2-dioxaphosphorinane) ring. This mechanism is contrasted to that for the previously reported triplet-sensitized photorearrangements of phosphites 1 and 7, which have greatly different phi P values. For these reactions, kinetic formation of the triplet analogue of 21, but without the tert-butyl substituent, requires a permutation of substituents for conversion to diradical 16 prior to intersystem crossing and beta scission to form the phosphonate corresponding to 7. The preparative-scale SET-induced photorearrangement of the thymidine-based 2-phenylallyl 3',5'-phosphite 10 gave both diastereomers of phosphonate 11 that were separated by HPLC. The 2-phenylallyl functionality provides an opportunity for further functionalization. As reported elsewhere, 11 was not formed in useful amounts via triplet-sensitized reaction of 10.

New photochemical and free radical reactions are applied to the synthesis of dinucleoside 2-phenylallylphosphonates and prenucleotide model vinylphosphonate systems.

In order to further understand the structural role of the modified nucleoside dihydrouridine in RNA the solution conformations of Dp and ApDpA were analyzed by one- and two-dimensional proton NRM spectroscopy and compared with those of the related uridine-containing compounds. The analyses indicate that dihydrouridine significantly destabilizes the C3'-endo sugar conformation associated with base stacked, ordered, A-type helical RNA. Equilibrium constants (Keq = [C2'-endo]/[C3'-endo]) for C2'-endo-C3'-endo interconversion at 25 degrees C for Dp, the 5'-terminal A of ApDpA and D in ApDpA are 2.08, 1.35 and 10.8 respectively. Stabilization of the C2'-endo form was shown to be enhanced at low temperature, indicating that C2'-endo is the thermodynamically favored conformation for dihydrouridine. DeltaH values show that for Dp the C2'-endo sugar conformation is stabilized by 1.5 kcal/mol compared with Up. This effect is amplified for D in the oligonucleotide ApDpA and propagated to the 5'-neighboring A, with stabilization of the C2'-endo form by 5.3 kcal/mol for D and 3.6 kcal/mol for the 5'-terminal A. Post-transcriptional formation of dihydrouridine therefore represents a biological strategy opposite in effect to ribose methylation, 2-thiolation or pseudouridylation, all of which enhance regional stability through stabilization of the C3'-endo conformer. Dihydrouridine effectively promotes the C2'-endo sugar conformation, allowing for greater conformational flexibility and dynamic motion in regions of RNA where tertiary interactions and loop formation must be simultaneously accommodated.

The chair-chair conformational equilibria (A reversible arrow B) of a series of 1,3,2-dioxaphosphorinanes featuring three-coordinated phosphorus substituted with an isoPr(2)N group (1-6) have been studied by H-1 NMR spectroscopy. Substituents at N(3) included Ph, Me, and isoPr. Compared to the analogous series with an Me(2)N group on phosphorus, 1-6 populate the chair conformation B with R(2)N equatorial to a greater extent. This is interpreted to mean that conformer A is more destabilized by the greater steric size of isoPr(2)N than is conformer B. Thus, the repulsive interactions between equatorial Me(2)N and the substituent on N3, believed to be responsible for depopulation of B that results in an unexpectedly high population of A with Me,N on phosphorus, is overcome by destabilization of A by the axial isoPr(2)N. The apparent size effect of substituents on N3 in destabilization of B follows the order Ph > isoPr > Me, as observed earlier for the series with a Me,N group on phosphorus. (C) 1996 John Wiley & Sons, Inc.

The O-17 chemical shifts of the title compounds cover a range of values and appear to be useful for the assignment of structure. However, the individual diastereomers of derivatives containing a stereogenic phosphorus center did not display discernably different O-17 chemical shifts.

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Attempted preparation of phosphorane 9 with a 1,3,2-dioxaphosphorinane ring attached diequatorially to phosphorus led to a mixture of products from which was isolated 12-membered ring phosphorane 10, formally the dimer of 9, in low yield (22%). An X-ray crystal structure of 10 revealed a highly symmetrical molecule with trigonal bipyramidal geometry at both phosphorus atoms. The 12-membered ring is attached to phosphorus diequatorially. The ring is strongly puckered about phosphorus with an equatorial O-P-0 angle of 110-degrees. The chemical shift equivalence of the CH2O resonances in the H-1 NMR spectrum of 10 shows the 12-membered ring to be highly mobile at ambient probe temperature. At -89-degrees-C, these resonances are fully decoalesced. The value of DELTAG(double dagger) for the process that averages these peaks was found to be 10.1 kcal/mol at coalescence (-42.O-degrees-C).

A series of phosphoranes, 5, 6a, 6b, and 7a, has been prepared and structurally characterized by H-1 NMR spectroscopy and/or X-ray crystallography. In the crystalline state, 5a, 6a, and 6b feature five-coordinate phosphorus bonded in a somewhat distorted, trigonal bipyramidal fashion. The phosphorus-containing six-membered ring is attached to phosphorus diequatorially and is in the chair conformation. H-1 NMR coupling constants reveal that for all four phosphoranes a chair-form ring, rather than a boat or twist conformation, also is populated in solution. The six-membered ring for 5 in solution is primarily in conformation 5a (ca. 90%) in equilibrium with 5b (ca. 10%). Arguments are presented to explain the greater stability of 5a in terms of reduced steric repulsion between its axial-like four-membered ring oxygen with the axial hydrogens of the phosphorus-containing ring compared to that of the analogous oxygen of the five-membered ring in 5b. The trans-fused ring structures of 6a, 6b, and 7a are closely related to the previously reported phosphoranes 1-3, prepared as transition-state analogs for the hydrolysis of cAMP. The results of the present paper render highly unlikely the assertion that thymidine-based phosphorane 3 populates in solution measurable amounts of a permutational isomer with its ring attached to phosphorus in diequatorial fashion. Structural aspects of the five-membered rings of phosphoranes 6a, 6b, and 7a also are discussed.

The chair-chair equilibria for a series of 5,5-dimethyl-2-oxo-(2-p-X-anilino)-1,3,2-oxazaphosphorinanes were determined by H-1 NMR. The percentage of chair conformer with the p-X-anilino group axial is increased by the presence of electron withdrawing X, while the opposite is true for electron-donor para X. Reasonably good linear plots of log K vs sigma-p were obtained in the solvents acetone-d6, CD3CN, and CD3NO2 with rho = 0.28-0.36. These results are interpreted in terms of the dominance of the endo anomeric effect involving overlap of the endocyclic N(3) and O(1) p lone pairs with the axial P-N sigma* orbital (p-XC6H4NHP).

The conformations of a series of 5,5-dimethyl-2-Z-1,3,2-oxazaphosphorinanes (Z = MeO, (CF3)2CHP, Ph, Me2N, and i-Pr2N) have been investigated by 1H NMR spectroscopy and by X-ray crystallography. Surprisingly, Me2N displays a strong preference for axial attachment to the ring; and i-Pr2N also is axial to a large extent (50%).

A series of nucleoside cyclic 3',5'-phosphoramidates has been studied by H-1 NMR spectroscopy. For cis-9-20 a chair-twist equilibrium has been characterized for the six-membered 1,3,2-dioxaphosphorinane (phosphoramidate) ring. The chair-twist equilibrium constant was estimated on the basis of the proton-phosphorus coupling constants for the 5'a and 5'b protons and found to vary with the nature of the amino group on phosphorus, the solvent, and to a lesser degree, the 2'-substituent (H or OH), and the heterocyclic base (purine or pyrimidine). The replacement of a pyrimidine base (uracil) with a purine base (adenine) shifts the equilibrium toward the chair conformation by only 0.1-0.3 kcal/mol. The presence of a 2'-OH also favors the chair form to a small extent (0.2-0.4 kcal/mol). The observed equilibrium constant for the N,N-dimethyl phosphoramidate derived from thymidine is used to estimate an intrinsic resistance of the six-membered ring to chair to twist interconversion (DELTA-G-degrees(C --> T)) in three solvents of only 0.5-0.8 kcal/mol. Correction of this value by 0.5 +/- 0.2 kcal/mol (change of base and 2'-substituent) gives an estimated DELTA-G-degrees(C --> T) for cAMP of 0.8-1.5 kcal/mol. Similarly corrected, the value of DELTA-G-degrees(C --> T) for cAMP, based on the previously studied trans phenyl cyclic 3',5'-phosphate derived from thymidine, becomes 2.5-2.9 kcal/mol. The potential for chair-twist conversion on binding of cAMP to an enzyme is pointed out, although no experimental evidence regarding this question exists. trans-9-20 all are shown to exist in the chair conformation. H-1 NMR reveals no evidence for conformational change in the sugar rings of these molecules on chair to twist conversion. The relative destabilization order for an axial amino substituent in the series 9-20 was found to be Me2N > piperidinyl > PhCH2NH > PhNH.

Compounds containing pentacovalent phosphorus in six-member rings have been synthesized. These are structural models for potential enzyme or substrate adducts of CAMP. The presence of twist rather than chair form P(V) containing rings was demonstrated by 1H NMR analysis.

17O NMR spectra of the title compounds show well-separated P=O17 peaks and configurationally diagnostic δ17O values and line widths. Use of these features to assign configurational purity to (17O, 18O) P-chiral nucleoside monophosphate diesters is proposed.

AbstractAssignments of cis or trans geometries of the trans‐ and cis‐phosphorinanes (I) and (II) are made by 31P and 1H NMR combined with X‐ray analysis for cis‐(IIb) (R: ‐H) (space group Pbca with Z = 8) and cis‐(IIb) (R: ‐Ph) (published elsewhere).

Direct cyclization of the title nucleosides with (Me2N)3P followed by oxidation with N2O4 or t-BuOOH affords the individual cyclic 3′,5′-phosphoramidate diastereomers shown to be isolable in 45-77% yields.

AbstractThe O2/AIBN oxidation of the simple system (I) and the thymidine‐based phosphite (III) is highly regio‐ and stereospecific, proceeding with retention of configuration at phosphorus and in yields equivalent to those obtained with the classical I2/H2O method.

AbstractThe photorearrangement of benzyl dialkylphosphites such as (I) yields the dialkyl benzylphosphonates (II) via a clean and regiospecific process.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformations of saturated six-membered ring phosphorus heterocycles. 2-Aryl-1,3,2-.lambda.5-oxazaphosphorinanesWesley G. Bentrude, William N. Setzer, Alan E. Sopchik, Subramanian. Chandrasekaran, and Michael T. AshbyCite this: J. Am. Chem. Soc. 1988, 110, 21, 7119–7127Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ja00229a027https://doi.org/10.1021/ja00229a027research-articleACS PublicationsRequest reuse permissionsArticle Views826Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

An investigation of the effects of changing the nature of X, nitrogen base (B), and amino substituent (R2N) on the equilibrium 1⇆2 was carried out. The influence of the above structural changes on the time-averaged coupling constants JAP and JBP, determined at 300 MHz, were used to follow changes in Keq. With constant R2N, small effects from variation of X and B were found. A large range in Keq arose from changes in the steric size of R2N. These results will be related to the question of the ease of chair to twist interconversion of the phosphate ring essential to the biological activities of the naturally occurring diesters, cAMP and cGMP.

Le compose du titre cristallise dans le systeme monoclinique, groupe C2 et sa structure est affinee jusqu'a R=0,039. Conformation anti de la base thymine. Conformation T 4 3 du cycle ribose et choise aplati du cycle phosphonate