[Stereochemistry of substituting the allyl hydroxyl group with fluorine atom in prostaglandins. Synthesis of 15-fluoro-11,15-dideoxyprostaglandins E1].
(+/-)-15-Fluoro-11,15-dideoxyprostaglandin E1 and its methyl and ethyl esters were synthesized. Dehydroxyfluorination reaction (+/-)-11-deoxyprostaglandin E1 esters with various reagents based on SF4 was studied. Along with the target 15-fluorides (mixtures of alpha- and beta-epimers), products of allylic shift and dehydration in a ratio dependent on the fluorination agent were shown to be formed. With a morpholinotrifluorosulfuran-tris(morpholine)sulfonium trimethyldifluorosilicate mixture, the maximal excess (70%) of one of the 15-fluoro epimers was achieved. Possible mechanisms of dehydroxyfluorination of (+/-)-11-deoxyprostaglandin E1 esters with dialkylaminoflluorosulfurans were proposed. Methyl esters of 15-alpha-fluoro- and 15-beta-fluoro-11,15-dideoxyprostaglandin E1 exhibited moderate antiaggregation activity in rabbit platelet tests.
Bezuglov
V V
VV
Pashinnik
V E
VE
Tovstenko
V I
VI
Markovskiĭ
L N
LN
Freĭmanis
Ia F
IaF
Serkov
I V
IV
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism
C104093:15-fluoro-11,15-dideoxyprostaglandin E1; D010975:Platelet Aggregation Inhibitors; D000527:Alprostadil