Stability of prostacyclin analogues: an unusual lack of reactivity in acid-catalyzed alkene hydration.
Prostacyclin analogue 5 undergoes specific acid-catalyzed hydration (kH+ = 1.9 x 10(-7)M-1 sec-1 at 25 degrees C) and a pH-independent oxidation reaction (k0 = 1.2 x 10(-10) sec-1 at 25 degrees C) above pH approximately 5. The hydration reaction for 5 is much slower than for other structurally similar exocyclic alkenes, even though the rate-determining step is proton transfer. This slowness of reaction and an analysis of the pH-rate profile show that 5 does not exhibit significant intramolecular general acid catalysis, as does prostacyclin.
Magill
A
A
Institute of Organic Chemistry, Syntex Research, Palo Alto, California 94304.
O'Yang
C
C
Powell
M F
MF
D000143:Acids; D000475:Alkenes; D002384:Catalysis; D004355:Drug Stability; D011464:Epoprostenol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis / Q000494:pharmacology*; D011522:Protons; D013237:Stereoisomerism; D013696:Temperature
D000143:Acids; D000475:Alkenes; D007783:Lactones; D011465:Prostaglandins, Synthetic; D011522:Protons; D011464:Epoprostenol