First synthesis and characterization for the stereoisomers of Ulipristal acetate
The three stereoisomers, 11α,17α-isomer I, 11α,17β-isomer II and 11β,17β-isomer III are related substances of the selective progesterone receptor modulator Ulipristal acetate. Herein, we presented an efficient and practical synthesis approach to deliver these three stereoisomers for the first time, and also confirmed the structure of the key intermediate 5a by single-crystal X-ray analysis. Our research will be of immense help for organic chemists to study the impurity profile of Ulipristal acetate.
A three-step synthesis of estra-4,9-diene-3,17-dione
Estra-4,9-diene-3,17-dione, an important pharmaceutical intermediate, was synthesized by a three-step sequence from δ-lactone 1 in 23.4% overall yield. Reaction of δ-lactone 1 and Grignard reagent 2 followed by treatment with Jones reagent resulted in precursor 4. The domino cyclization reaction of 4 with piperidinium acetate gave estra-4,9-diene-3,17-dione.
Ulipristal Acetate Taken 48–120 Hours After Intercourse for Emergency Contraception
OBJECTIVE: To evaluate the efficacy and safety of ulipristal acetate as emergency contraception in women presenting 48–120 hours after receiving ulipristal acetate for unprotected intercourse. METHODS: Women aged 18 years or older with regular cycles who presented for emergency contraception 48 to 120 hours after unprotected intercourse were enrolled in 45 Planned Parenthood clinics and treated with a single dose of 30 mg ulipristal acetate. Pregnancy status was determined by high-sensitivity urinary human chorionic gonadotropin testing and return of menses. RESULTS: A total of 1,241 women were evaluated for efficacy. Twenty-six were pregnant at follow-up, for a pregnancy rate of 2.1% (95% confidence interval 1.4–3.1%). These results satisfy the protocol-defined statistical criteria for success because the pregnancy rate was lower than both the estimated expected pregnancy rate and a predefined clinical irrelevance threshold. In addition, efficacy did not decrease over time: pregnancy rates were 2.3% (1.4–3.8%), 2.1% (1.0–4.1%), and 1.3% (0.1–4.8%) for intervals of 48 to 72 hours, more than 72 to 96 hours, and more than 96 to 120 hours, respectively. Adverse events were mainly mild or moderate, the most frequent being headache, nausea, and abdominal pain. Cycle length increased a mean of 2.8 days, whereas the duration of menstrual bleeding did not change. CONCLUSION: Ulipristal acetate is effective and well-tolerated for emergency contraception 48–120 hours after unprotected intercourse. LEVEL OF EVIDENCE: II