化学选择性还原21-叠氮基皮质激素法制备21-伯胺基皮质激素

Chemoselective Reduction of 21-Azidocorticosteroids to Primary 21-Primary Aminocorticosteroids

以锌 /氯化铵为还原剂 ,在含水四氢呋喃中将 2 1 -叠氮基皮质激素化学选择性地还原为 2 1 -伯氨基皮质激素 . 1 1 β-羟基 -2 1 -叠氮基皮质激素比相应的 1 1 -酮基和 1 1 -去氧皮质激素容易还原 ,含水四氢呋喃是该反应的最适合溶剂 ,水的含量在还原体系中起着极其重要的作用 .

The chemoselective reduction of 21-azidocorticosteroids to the corresponding 21-primary aminocorticosteroids was achieved with Zn/NH 4Cl as a reductant in reasonable yields(70%—85%). 11β-Hydroxyl-21-azidocorticosteroids were found to be easier to reduced to their amino counterparts more easily than 11-carbonyl and 11-deoxyl-21-azides. Aqueous THF was found to be the most suitable solvent for this reaction, and the ratio of water in the reducing system was crucial. In THF of 95%—97% in volume fraction and at 15 ℃, Zn/NH 4Cl can only reduce 11β-hydroxyl-21-azidocorticosteroids. To reduce the 11-carbonyl and 11-deoxy-21-azides, the volume fraction of water should be raised to 10% at least. This reduction method has the advantages of rather mild conditions, cheap and easily accessible reagents, and reasonable overall yields. Moreover, its simple work up and easy manipulation in large scale make our method superior to the reported Gabriel and 21-aldehyde oxime reduction procedures in the literature.