15847-24-2Relevant articles and documents
Δ1-dehydrogenation and C20 reduction of cortisone and hydrocortisone catalyzed by rhodococcus strains
Costa, Stefania,Fantin, Giancarlo,Semeraro, Bruno,Summa, Daniela,Zappaterra, Federico
, (2020)
Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. ruber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20β-hydroxy-prednisone and 20β-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.
Synthesis of new antiinflammatory steroidal 20-carboxamides: (20R)- and (20S)-21-(N-substituted amino)-11β,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene
Kim,Bird,Heiman,Hudson,Taraporewala,Lee
, p. 2239 - 2244 (2007/10/02)
The synthesis and antiinflammatory activities of new steroidal 20-carboxamides, (20R)- and (20S)-21-(N-substituted amino)-11β,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene (5-8) are described. These compounds were prepared from the respective isomer of 20-dihydroprednisolonic acid, (20R)- and (20S)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oic acid (4a and 4b), by coupling with primary amines after the activation of the steroid acid with N,N1-dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole. Confirmation of the configurational assignment at C-20 of the 20-carboxamides was achieved by reduction of methyl (20R)- and (20S)-11β,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate (3a and 3b) to the known stereochemistry at C-20 of (20R)- and (20S)-11β,17,20,21-tetrahydroxy-3-oxo-1,4-pregnadiene (2a and 2b). The topical antiinflammatory activities of these steroidal 20-carboxamides were assessed by the croton oil induced ear edema assay and their local and systemic antiinflammatory activities by the cotton pellet granuloma bioassay. Results of these investigations suggest a structure-activity relationship where carboxamide derivatives with the 20(R)-hydroxy configurations exhibit higher potency than those with the 20-(S)-hydroxy configurations. The amides of steroidal 21-oic acids with high local antiinflammatory potency exhibited systemic activities unlike the corresponding esters of steroidal 21-oic acids, which are devoid of systemic activities.
