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Abstract
Background: 16-Dehydropregnenolone acetate (16-DPA) is a typical intermediate compound in the production of many semisynthetic steroid drugs such as sex hormones, corticosteroids, 5α-reductase inhibitors, and several other biologically active steroid groups. Due to its complex structure and difficulty in chemical synthesis, 16-DPA is mainly produced from steroid sapogenins found in medicinal herbs such as diosgenin, solasodine... Objectives: Synthesize 16-DPA from diosgenin as raw material to prepare steroid drugs. Methods: 16-DPA was synthesized from diosgenin through 2 stages: i) acetylation of diosgenin in acetic anhydride to form intermediate diosgenin acetate (DA), then ring-opening acetylation by adding aluminum chloride and boric acid to obtain pseudodiosgenin diacetate (PDA); ii) Oxidation of PDA by potassium permanganate to create diosone, followed by hydrolysis in acetic acid to obtain 16-DPA. Structure of intermediate derivatives and final 16-DPA was confirmed by spectroscopic techniques: mass spectrometry (MS), infrared (IR), and nuclear magnetic resonance (1H- and 13C-NMR). Results: In the initial stage, PDA was successfully synthesized without requiring pressure at 140°C in 90 minutes in 45% yield as a white crystalline powder, Rf 0.52 (n-hexane/ethyl acetate, 4/1), mp. 98.0 - 100.0°C. In the second stage, 16-DPA was obtained in 92.3% yield without the need for column chromatography, final product as a white crystal, Rf 0.60 (n-hexane/ethyl acetate, 1/1), mp. 172.0 - 173.0°C. The 1H-NMR and 13C-NMR spectra perfectly match the previously published data. Conclusions: 16- DPA was successfully synthesized from diosgenin with a total yield of 41.5%. The structures of intermediate an final product 16-DPA were proven by spectroscopic analysis. The synthesis procedure shows promise for scaling-ups the process with the potential to apply in the synthesis of steroid drugs.
| Published | 2025-09-30 | |
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| Issue | Vol. 4 No. 3 (2025) | |
| Section | Original article | |
| DOI | 10.66517/jstmp.2025.3.7 | |
| Keywords | Diosgenin, Diosone, Steroids, Pseudodiosgenin diacetate Diosgenin, Diosone, Steroids, 16-DPA, Pseudodiosgenin diacetate |
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