Submit Manuscript  

Article Details


An Efficient Procedure for the Synthesis of 21-Acetoxypregna-1,4,9(11),16- tetraene-3,20-dione

Author(s):

Luu D. Huy*, Nguyen T. Diep, Tran K. Vu, Tatiana S. Savinova and Marina V. Donova   Pages 1 - 7 ( 7 )

Abstract:


Background: Halogenated corticosteroids are widely used in medicine, and the global needs in these steroidal APIs are estimated in 40 – 70 tons, annually. Vietnam currently imports the pharmaceutical compounds up to 90%, in particular 100% of steroidal drugs. Currently, industrial production is based on the chemical syntheses of corticosteroids from either 16-dehydropregnenolone acetate (obtained from diosgenin) or androstenedione (obtained from phytosterol). The development of shorter synthetic schemes and more economically feasible technologies is of great significance. Introduction of 1(2)-double bond at the final stages of the corticosteroids synthesis resulted in its poor yield. 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione (tetraene acetate) is a key intermediate in the synthesis of highly active halogenated corticosteroids such as dexamethasone and other halogenated corticosteroids. 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione, a key intermediate in the synthesis dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione.

Objective: The purpose of this study was development of efficient and shorter procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, which is a product of a bio-oxidative degradation of the side chain of phytosterols.

Methods: Pregnane side chain was constructed using cyanohydrin method. For 1(2)-dehydrogenation, selene dioxide was applied for introduction of Δ1(2)-double bond. epimerization, Stork’s iodination procedure and dehydratation. Other stages of the synthesis were epimerization, Stork’s iodination procedure and dehydratation.

Result: 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione was prepared from 9α-hydroxyandrostenedione in yield more than 46%.

Conclusion: An efficient and practically feasible procedure for the synthesis of 21-acetoxypregna-1,4,9(11),16-tetraene-3,20-dione from 9α-hydroxyandrostenedione, a key intermediate for synthesis of the 9-haloidated corticoids has been developed. The results could be applied at the production of the value-added 9-haloidated corticoids.

Keywords:

9α-hydroxyandrostenedione, 21-acetoxypregna-1, 4, 9(11), 16-tetraene-3, 20-dione, Dehydration, Hydrocyanation, Acetoxylation, Dehydrogenation

Affiliation:

Institute of Chemistry, Vietnam Academy of Science and Technology, 18- Hoang Quoc Viet, Cau giay, Hanoi, Institute of Chemistry, Vietnam Academy of Science and Technology, 18- Hoang Quoc Viet, Cau giay, Hanoi, School of Chemical Engineering, Hanoi University of Science and Technology, No 1, Dai Co Viet, Hai Ba Trung-Hanoi, M. V. Lomonosov Moscow State University, Faculty of Chemistry Build. 3, 1 Lenin Hills, 119991 Moscow, Federal Research Center «Pushchino Center for Biological Research of the Russian Academy of Sciences», G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki, 5, 142290, Pushchino, Moscow region



Read Full-Text article