Homonuclear one- and two-dimensional nuclear Overhauser effect experiments and spin-echo correlated spectroscopy. Application to prostaglandin E₁ and 6-keto-prostaglandin E₁

Abstract

GEORGE KOTOVYCH and GERDY H. M. AARTS. Can. J. Chem. 60,2617Chem. 60, (1982 Nuclear Overhauser effect one-dimensional and two-dimensional nuclear magnetic resonance experiments are reported for prostaglandin E l . The two-dimensional nuclear Overhauser effect measurements are combined with spin-echo correlated spectroscopy in order to assign the complete high-field proton magnetic resonance spectrum of 6-keto-prostaglandin E,. The advantages of these two-dimensional techniques are illustrated in these studies. It is also observed that the 6-keto-prostaglandin E l H-loci proton is substituted more readily by deuterium than are the other protons a to the keto groups. Chem. 60,2617Chem. 60, (1982. On rapporte des experiences en rmn sur I'effet Overhauser nucleaire a une e t a deux dimensions pour la prostaglandine E l . Les mesures de l'effet Overhauser nucleaire sont combinees avec la spectroscopie spin-echo de correlation dans le but d'identifier le spectre complet de resonance magnetique du proton a haut champ de la ceto-6 prostaglandine E l . On illustre dans ces etudes les avantages de ces techniques a deux dimensions. On a Cgalement observe que le proton H-lOa de la prostaglandine E, est substitue plus facilement par le deuterium que les autres protons en a des groupes cetoniques.[Traduit par le journal]Prostacyclin (Prostaglandin I,, PGI,) is the most potent inhibitor of platelet aggregation and a potent vasodilator (1, 2). It is unstable and rapidly hydrolyses to 6-keto-prostaglandin F,,. The metabolism of PGI, or 6-keto-prostaglandin F,, by 9-hydroxyprostaglandin dehydrogenase in human platelets leads to a more stable substance, 6-keto-prostaglandin El (6-keto-PGE,) (3) with similar biological activity to PGI, (4, 5). In our continuing studies of the structure-activity relationships of PGI, and its derivatives, we found it very difficult to analyze the complete proton magnetic resonance spectrum of 6-keto-PGE,. Even at 400 MHz, due to the overlap of the multiplets in the high-field region, standard decoupling and one-dimensional nuclear Overhauser effect (nOe) measurements could not be used to assign all of the proton resonances. The complete assignment was possible by means of the combined two-dimensional nOe measurements and spin-echo correlated spectroscopy (SECSY).The selective proton-proton one-dimensional (ID) nOe experiments have been extensively applied in the study of molecular structure and conformation (6-9). This experiment requires the measurement of the intensity change of a proton resonance upon saturating another proton. Twodimensional nOe experiments have recently been developed for the investigation of cross-relaxation 'Paper No. 9 in a series of high-field nmr studies on the prostaglandins and vitamins. For paper No. 8, see ref. 31. and chemical exchange processes (10-15). The advantages of this technique over the one-dimensional nOe experiment are (a) the simultaneous measurement of all the nOe's between closelyspaced protons in a molecule, and (b) the elimination of problems assoc...

Prostaglandins, thromboxanes, leukotrienes, and related arachidonic acid metabolites

“…The conjugate addition of the allylic carbanion derived from 1 -phenylthio-oct-2-ene (29) to the cyclopentanone (30) in hexamethylphosphoramide has been reported to give the adduct (31).37 Oxidation of (31) to the sulphoxide derivative (32), followed by sulphoxide-sulphenate rearrangement and deprotection, furnished PGEl methyl ester. It is worth noting, however, that similar conjugate addition of the carbanion that is derived from the sulphoxide (33) and the 1 1-deoxy-analogue of (30) gave the 1,4-y-adduct (34) as the major product.…”

“…29 Under this condition, LTA, can be converted into LTD,, using a cell-free epoxide hydrolase from rat basophilic leukaemia cells. 30 The levels of the glutathione-S-transferase and the yglutamyl transpeptidase activity in guinea-pig lung and rat basophilic leukaemia cells have been reported. Two other classes of leukotrienes have been reported.…”

Further Oxygenated Fatty Acids from Lemna minor

“…Low resolution ms gave a satisfactory fragmentation pattern and hrms (mtz 312.1943) gave a molecular formula of C17H2805. Although the 'H-nmr spectrum was complex, decoupling and nOe experiments allowed most of the signals to be assigned based on the chemical shifts reported for prostaglandin (5). In particular, irradiation of the H-ll at 4.06 caused the H-12a and -12ß multiplets to collapse into two doublets (/= 18.2 Hz) centered at 2.18 and 2.70, respectively, while the H-10 multiplet at 2.36 was simplified.…”