Gemeprost, a metabolically stabilized analog of PGE1, has been demonstrated to
reliably induce termination of early pregnancy when administered as a vaginal
suppository. Its effect is presumably due to both uterine contraction and rapid
decline of steroid hormone levels. Minimal side effects have been reported.
Gemeprost is an analogue of Prostaglandin (P838600). Gemeprosts, similarly to Nitric Oxide donors, induce uterine cervical dilation and are used before surgical termination of pregnancy.
Synthesis of 9-oxo-1α,15α-bis-(2-tetrahydropyranyloxy)-16,16-dimethylprosta-trans-2, trans-13-dienoic acid: 4 g of ethyl 9α-hydroxy-11α15α-bis-(2-
tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-13-dienoate were
dissolved in 130 ml of a mixture of ethanol-water (3:1), mixed with 3.9 g of
potassium hydroxide and stirred at 25°C for 2 hours. The reaction mixture
was acidified with aqueous solution of oxalic acid to pH 5, and diluted with
100 ml of water, extracted with ethyl acetate. The extracts were washed with
water, dried over sodium sulfate and concentrated under reduced pressure to
obtain 3.88 g of 9α-hydroxy-11α,15α-bis-(2-tetrahydropyranyloxy)-16,16-
dimethyl-prosta-trans-2,trans-13dienoic acid.
The obtained compound 2.46 g were dissolved in 72 ml of diethyl ether and
stirred at 3°C. To which a solution of manganese sulfate (15 g), 3.1 g of
chromium trioxide, 72 ml of water and 3.5 ml of sulfuric acid was added. After
stirring for 3.5 hours at 3°C, extracted with diethyl ether. The organic layer
was washed with water, dried over sodium sulfate and concentrated under
reduced pressure. The residue was purified by column chromatography on
silica gel using ethyl acetate-benzene (1:1) as eluent to give 2.35 g of the
title compound.
Synthesis of 16,16-dimethyl-trans-δ2-PGE1: 2.35 g of the bistetrahydropyranyl ether were dissolved in 6 ml of tetrahydrofuran and 60 ml
of 65%-acetic acid aqueous solution and the solution stirred at 60°C to 70°C
for 20 minutes. The reaction mixture was extracted with ethyl acetate, and
the organic layer was washed with water, dried and concentrated under
reduced pressure. The residue was purified by column chromatography on
silica gel using ethyl acetate-cyclohexane (2:3) as eluent to yield 270 mg of
the title compound.
