A new and efficient method for the synthesis of Ulipristal acetate

Cheng, Xu; Li, Xiaocen; Duan, Yanjun; Yu, Yongguo; Li, Hai; Wu, Yong

doi:10.1016/j.steroids.2014.03.009

Cited by 7 publications

(4 citation statements)

References 7 publications

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“…Mifepristone and known steroid derivatives were synthesized as examples of analogues with different substituents at the 17-position whilst maintaining the 4-N,N-dimethylaniline moiety at the 11-position. These analogues included Ulipristal Acetate ( 21 ) 53,54 , Desmethyl-mifepristone ( 6) 55 , Trifluoromethylmifepristone ( 9 ) (where synthesis was modified from that described for a similarly related compound) 56 , along with Lilopristone ( 13 ) and Aglepristone ( 7 ); although they are commercially available, synthesis of the latter compounds has not been described, making the present study the first to report a method for their synthesis.…”

Section: Methodsmentioning

confidence: 99%

“…Supplementary Fig. S2 describes the most recent literature precedence for the synthesis of Ulipristal Acetate ( 21 ), beginning with the cyanohydrin diene-3-one 53 . Unfortunately, whilst the steps according to literature worked sequentially to deliver 17 in a good yield, TMS deprotection of 17 with HCl in acetone at 50 °C, resulted in two products 19 and 20 in the ratio of (5:3), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Synthesis of Ulipristal Acetate has been described by a number of research groups with varying methodology 53,54,64–66 , with successful synthesis of 21 achieved by adapting the approach from Dancsi et al . 64 , Kim et al .…”

Section: Methodsmentioning

confidence: 99%

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Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity

DeBono

Thomas

Lundberg

et al. 2019

Sci Rep

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There are currently no therapeutics to treat infection with the alphavirus Venezuelan equine encephalitis virus (VEEV), which causes flu-like symptoms leading to neurological symptoms in up to 14% of cases. Large outbreaks of VEEV can result in 10,000 s of human cases and mass equine death. We previously showed that mifepristone (RU486) has anti-VEEV activity (EC 50 = 20 μM) and only limited cytotoxicity (CC 50 > 100 μM), but a limitation in its use is its abortifacient activity resulting from its ability to antagonize the progesterone receptor (PR). Here we generate a suite of new mifepristone analogues with enhanced antiviral properties, succeeding in achieving >11-fold improvement in anti-VEEV activity with no detectable increase in toxicity. Importantly, we were able to derive a lead compound with an EC 50 of 7.2 µM and no detectable PR antagonism activity. Finally, based on our SAR analysis we propose avenues for the further development of these analogues as safe and effective anti-VEEV agents.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity

DeBono

Thomas

Lundberg

et al. 2019

Sci Rep

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“…In the pharmaceutical industry, some important steroid drug products have special structures at the C 10 ‐position compared to the 10β‐methyl group that most natural steroids possess. This includes retroprogesterone [1] with a 10α‐methyl group, as well as important androgen and estrogen steroids such as ethinyl estradiol, estradiol, [2] 19‐norsteroids [3–6] and Ulipristal acetate [7–9] without a methyl group at the C 10 ‐position.…”

Section: Introductionmentioning

confidence: 99%

A Keto Reductase Involved in Steroid Degradation in Mycolicibacterium neoaurum

Jin

Peng

Tian

et al. 2023

Chemistry & Biodiversity

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Phytosterols can be used by microorganisms as carbon and energy sources and completely degraded into CO 2 and H 2 O. The catabolic pathway of phytosterols was well characterized in many microorganisms. Blocking the steroid core ring degradation by deletions of fadE30 and fadD3 genes, two important steroid intermediates, 3aα-H-4α-(3'-Propionic acid)-5α-hydroxy-7aβ-methylhexahydro-1-indanone-δ-lactone (sitolactone, or HIL) and 3aα-H-4α-(3'-propionic acid)-7aβ-methylhexahydro-1,5-indanedione (HIP) can be accumulated. They are currently used to synthesize nor-steroid drugs with an α-methyl group or without the methyl group at the C 10 -position, such as estrone and norethindrone. In this study, a key gene involved in the bioconversion of HIP to HIL was identified in Mycolicibacterium neoaurum. Through heterologous expression, gene hipR was found to be involved in the reduction of the C 5 keto group of HIP to a hydroxy group, leading to spontaneously lactonization into HIL in vitro. Through gene complementation and knockout, HipR functions were verified and two HIP degradation pathways in vivo were elucidated. The finding of this research facilitated the understanding of the metabolic pathway of sterols, and was directly applied to engineering robust production strains by overexpression or knockout of related genes.

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