The alkaline hydrolysis of the P-chiral ds-nucleoside 3',5'-cyclic aryl [180] monophosphates 4a-c and of the unlabeled analogs 3a-c was studied. Hydrolysis of the 180-labeled phosphate triesters 4a-c yielded three products: 3',5'-cyclic [180]phosphate diester, S'-acyclic and [180]phosphate diester, and 3'-acyclic aryl [180]phosphate diester. The stereochemistry of the formation of the 3',5'-cyclic [180] phosphate diester was determined by means of methylating the hydrolysis products with methyl iodide. The formation of the 3',5'-cyclic [180] phosphate diester during hydrolysis of compounds 4a and 4c proceeds with 17% inversion of configuration at phosphorus, whereas 40% inversion is found during hydrolysis of 4b. Inversion of configuration indicates the existence of a PV-TBP with a diequatorially located dioxaphosphorinane ring. Retention of configuration (83% for 4a and 4c, and 60% for 4b) can be explained in terms of Berry pseudorotation. The formation of the S'-acyclic aryl [180]phosphate diester during hydrolysis of compounds 4a and 4c proceeds with about 50% inversion of configuration at phosphorus, whereas formation of the 3'-acyclic aryl [180]phosphate diester proceeds with an inversion/retention ratio of 88:12 or 12:88 for 4a and 79:21 or 21:79 for 4c. It is clear that Berry pseudorotation takes place during hydrolysis of the 3',5'-cyclic phosphate triesters 4a-c. This is in contrast with earlier hydrolysis studies on 3',5'-cyclic phosphate diesters proceeding without Berry pseudorotation, leading to complete inversion of configuration at phosphorus. Because of the very small amounts of 3'and S'-acyclic aryl [180] phosphate diesters formed during the hydrolysis reaction of compound 4b, the stereochemistry could not be determined. The hydrolysis reactions, which have been studied on the unlabeled compounds 3a-c, obey second-order kinetics. Changing the ribose ring to a deoxyribose ring or changing the adenine base to thymine in the 3',5'-cyclic phosphate triester does not dramatically influence the second-order reaction rate constant. However, the nature of the P-OR substituent significantly influences the reaction rate. The 3',5'-cyclic phosphate triester with p-nitrophenoxy as substituent hydrolyzes approximately 18 times ( = 294 K) faster than the corresponding triester with phenoxy as substituent.

Chem. 71, 855 (1993). This study is focussed on 2'-0-methyl-cis-adenosine 3',5'-cyclic methyl monophosphate (cis-4; cis describes the relationship between OMe (bound to phosphorus) and the adenine base), which is regarded a model for enzyme-bound cyclic adenosine monophosphate (CAMP). In this complex the negative phosphate Eharge is shielded in part via complexation with cationic sites on the enzyme surface. We report synthesis, crystal structure, solution conformation and N6-H...N7 hydrogen bonds in such a way that infinite one-dimensional chains are formed. This hydrogen bond scheme is very similar to that observed in the shucture of 2'-deoxy-3',5'-di-0-acetyl adenosine. An additional hydrogen bond is formed between methanol, incorporated in the crystal structure, and the adenine base. The conformational preferences of the cis-4 dissolved in methanol have been determined with 400 MHz 'H NMR. It is found that the conformations observed in the solid and solution states are practically the same. Hydrolysis of the title compound yields two acyclic phosphate diesters (a 3'-and a 5'-phosphate diester). 'The intermediates formed during the hydrolysis reaction are most likely five-coordinated phosphorus (P") compounds with a trigonal bipyramidal geometry and an equatorial-axial located 3'3'-dioxaphosphorinane ring.NIEK L.H.L. BROEDERS, ARTHUR P. VAN 855 (1993).La prksente etude est orientte vers le monophosphate cyclique-3',5' de methyle de la 2'-0-methyl-cis-adenosine (cis-4; cis se refkre 2 la relation entre le OMe (lie au phosphore) et la base adenine) qui est consider6 comme un modble pour le monophosphate cyclique de l'adenosine liee a un enzyme (CAMP). Dans ce complexe, la charge negative du phosphate est masqute en partie par une complexation avec les sites cationiques sur la surface de l'enzyme. On rapporte la synthese et des etudes sur la determination de la structure, de la conformation en solution (400 MHz, RMN du 'H) et des aspects cinetique-mecanisme de l'hydrolyse alcaline du produit cis-4. La produit de solvatation de cis-4 avec du methanol cristallise dans le Froupe d'espace orthorhombique P2,2,2, avec a = 8,170(2), b = 9,249 (1) d'une fagon telle qu'il y a formation de chaines unidimensionnelles infinies. Cette arrangement par liaisons hydrogbnes est trks semblable 2 celui observe dans la structure de la 2'-dCsoxy-3',5'-di-0-acetyl adenosine. Une liaison hydrogbne additionnelle se forme avec le methanol, incorpore dans la structure cristalline, et la base adenine. Faisant appel a la RMN du 'H, a 400 MHz, on a determine les preferences conformationnelles du produit cis-4 en solution dans le methanol. On a trouve que les conformations observees en phase solide et en solution sont les m&mes. L'hydrolyse du compose mentionnk dans le titre fournit deux esters acycliques de l'acide phosphorique (un diester 3'-et un diester 5'-phosphate). Ces intermediaires qui se forment durant la reaction d'hydrolyse sont probablement des composCs pentacoordines du phosphore (P") de geometric bipyramidale trigonale et...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.