BACKGROUND Halogenated corticosteroids are widely used in medicine, and the global need of these steroidal APIs is estimated to be 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 results inpoor 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 is a key intermediate in the synthesis of dexamethasone from the readily available and cheap 9α-hydroxyandrost-4-ene-3,17-dione. OBJECTIVE The purpose of this study was the development of an 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 the introduction of Δ1(2)-double bond. Other stages of the synthesis were epimerization, Stork's iodination procedure and dehydration. 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 the synthesis of 9-haloidated corticoids, has been developed. The procedure can be applied for the production of value-added 9-haloidated corticoids.

中文翻译：

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一种合成21-乙酰氧孕烯-1,4,9（11），16-四烯-3,20-二酮的有效方法。

背景技术卤代皮质类固醇广泛用于医学中，并且估计这些类固醇API的全球需求每年为40-70吨。越南目前进口的药用化合物高达90％，尤其是甾体药物的100％。当前，工业生产基于由16-脱氢孕烯醇酮乙酸酯（从薯os皂素获得）或雄烯二酮（从植物甾醇获得）的皮质类固醇的化学合成。开发更短的合成方案和更经济可行的技术具有重要意义。在皮质类固醇合成的最后阶段引入1（2）-双键会导致收率低下。21-Acetoxypregna-1,4,9（11），16-tetraene-3，20-二酮（乙酸四烯酯）是合成高活性卤代皮质类固醇（如地塞米松和其他卤代皮质类固醇）的关键中间体。21-acetoxypregna-1,4,9（11），16-tetraene-3,20-dione是从容易获得且便宜的9α-羟基androst-4-ene-3,17-dione合成地塞米松的关键中间体。目的本研究的目的是开发一种有效且较短的程序，以从9α-羟基雄烯二酮中合成21-乙酰氧基孕烯-1,4,9（11），16-四烯-3,20-二酮固醇侧链的生物氧化降解作用。方法采用氰醇法制备孕烷侧链。对于1（2）-脱氢反应，将二氧化硒用于引入Δ1（2）-双键。合成的其他阶段是差向异构，鹳的加碘程序和脱水。结果由9α-羟基雄烯二酮制备了21-乙酰氧孕烯-1,4,9（11），16-四烯-3,20-二酮，收率超过46％。结论从9α-羟基雄烯二酮（一种合成9-卤代皮质类固醇的关键中间体）合成21-乙酰氧基孕烷-1,4,9（11），16-四烯-3,20-二酮的有效方法，在实践中是可行的，已经被开发出来。该程序可用于生产增值的9卤代皮质类固醇。已经开发出用于合成9-卤代皮质激素的关键中间体。该程序可用于生产增值的9卤代皮质类固醇。已经开发出用于合成9-卤代皮质激素的关键中间体。该程序可用于生产增值的9卤代皮质类固醇。