Synthesis of Levonorgestrel: A New Strategy to Construct the Key 13β-Ethyl Steroid Precursor

Organic Process Research & Development 2026

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Authors: Hongmiao Yao, Jie Wang, Yuanhao Chen, Ziyue Zhang, Yinqi Huang, Jian Wang, Wen Jin, Bu-Bing Zeng
DOI: 10.1021/acs.oprd.5c00438
Cited by: 0
References: 55

Abstract

Levonorgestrel, a representative 13β-ethyl progestin, poses a synthetic challenge due to the construction of its 13β-ethyl precursor. Herein, we report the chemical synthesis of the common 13β-ethyl precursor, (13 S,14 S )-13-ethyl-3-methoxy-6,7,11,12,13,14,15,16-octahydro-17 H -cyclopenta[ a ]phenanthren-17-one, in seven or eight steps from inexpensive 3-bromoanisole or 3-methoxybenzaldehyde. Key transformations include a Hajos–Wiechert-type reaction to introduce the chiral ethyl group, a Friedel–Crafts cyclization to form the B ring, and regio- and stereoselective hydrogenation. Starting from this 13β-ethyl precursor, levonorgestrel was subsequently obtained in four steps, including an ethylenediamine-mediated Birch reduction.

Fields of Study & Subjects

Steroid Chemistry and Biochemistry Organic Chemistry Synthesis Methods Asymmetric Synthesis and Catalysis

Publication details

Journal / source
Organic Process Research & Development
Volume
30
Issue
2
Pages
476–484
Publication date
11 February 2026
Language
EN