PENTACOVALENT PHOSPHORUS-CONTAINING MODELS OF P(V) H2O- OR ENZYME CAMP ADDUCTS - NONCHAIR CONFORMATIONS OF THE PHOSPHORUS-CONTAINING RINGS AS DETERMINED BY H-1-NMR SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY

A series of pentacovalent phosphorus-containing, P(V), molecules (3-6), designed as models of P(V) H2O-cAMP or enzyme-cAMP adducts (or transition states) were prepared and studied by NMR (3-6) and X-ray crystallography (6). The preparation of 3-6 by reaction of the phosphite precursors with (CF3)2CO or (CF3)2COCO(CF3)2 was shown to proceed with retention of configuration at phosphorus. The X-ray structure of 6 showed it to be close to trigonal bipyramidal with the six-membered, 1,3,2-dioxaphosphorinane ring attached equatorial/apical to phosphorus. The oxygen equivalent to the O5′ of cAMP is in the apical position. The ring is in a twist conformation in the crystal. 1H NMR measurements show the 1,3,2-dioxaphosphorinane ring of 3-6 to be in a nonchair (probably twist) conformation in solution as well. It is concluded that in solution the 1,3,2-dioxaphosphorinane ring of 3-6 is almost certainly apical/equatorial. It is also postulated that for a 1,3,2-oxaza- or dioxaphosphorinane ring attached apical/equatorial to phosphorus a nonchair (boat or twist) conformation is intrinsically more stable than the chair form. It is suggested that a likely principle role of phosphodiesterase in the catalyzed hydrolysis of cAMP is to assure the formation of a cAMP-H2O adduct with the water and P-O3′ bonds coapical. It is pointed out that if the O3′ apical twist form is formed enzymatically, the p-orbital lone pair on O5′ is lined up parallel to the apical bonding systems such that it could assist stereoelectronically in the formation of the P(V) adduct and in its rapid scission to form 5′-AMP. The possibility is suggested that cAMP may be bound in the twist form and the cAMP-H2O adduct may be formed directly there from in the twist conformation. © 1990, American Chemical Society. All rights reserved.