ABSTRACT
A facile synthesis of the side chain of loteprednol etabonate, namely, chloromethyl-17α-[(ethoxycarbonyl))oxy]-11ß-hydro of loteprednol etabonate, viz., chloromethyl-17α-[(ethoxycarbonyl))oxy]-11xy-3-oxoandrosta-1,4-diene-17ß-carboxylate--an ocular soft corticosteroid, has been described starting from a 20-oxopregnane, namely, 3ß-acetoxy-pregn-5(6),16(17)-diene-20-one (16-dehydropregnenolone acetate, i.e., 16-DPA) using our recently developed metal-mediated halogenation as a key reaction.
Subject(s)
Androstadienes/chemical synthesis , Pregnanes/chemistry , Adrenal Cortex Hormones , Anti-Allergic Agents , Halogenation , Loteprednol Etabonate , Metals , Optical DevicesABSTRACT
Cytochrome P450 (CYP) monooxygenase activities with different category of substrates namely, alkanes, alkane derivatives, alcohols, aromatic compounds, organic solvents, and steroids were detected in the cells of Aspergillus terreus. High CYP specific activity was observed when methanol (5.6+/-0.017 U mg(-1)), acetone (7.76+/-0.02 U mg(-1)), dimethylsulphoxide (DMSO) (9.70+/-0.005 U mg(-1)), n-hexadecane (4.39+/-0.02 U mg(-1)), or n-octadecane (4.23+/-0.01 U mg(-1)) were used as substrates. Significant CYP specific activity was also detected when naphthalene (3.80+/-0.002 U mg(-1)) was used as substrate. The CYP catalysis of n-hexadecane had followed both terminal and sub terminal oxidations. The activity was localized in the cytosol of n-hexadecane grown cells, while, it was apparently distributed in light mitochondrial fraction and microsomal fraction of glucose grown cells. The substrate specificities of CYP present in all the locations were similar irrespective of the substrates used for the growth. Heme staining of the microsomal fraction containing CYP and other proteins in SDS-PAGE showed single heme protein band with corresponding molecular weight of 110 kDa.
Subject(s)
Alkanes/metabolism , Aspergillus/enzymology , Cytochrome P-450 Enzyme System/metabolism , Mixed Function Oxygenases/metabolism , Acetone/metabolism , Cytochrome P-450 Enzyme System/analysis , Dimethyl Sulfoxide/metabolism , Electrophoresis, Polyacrylamide Gel , Heme/chemistry , Heme/metabolism , Hydrogen-Ion Concentration , Methanol/metabolism , Microsomes/enzymology , Mitochondria/enzymology , Mixed Function Oxygenases/analysis , Molecular Weight , Naphthalenes/metabolism , Oxidation-Reduction , Spectrophotometry , Substrate Specificity , Temperature , Time FactorsABSTRACT
Bromodimethylsulfonium bromide has been found to be an effective and regioselective reagent for alpha-monobromination of beta-keto esters and 1,3-diketones. A wide variety of beta-keto esters and 1,3-diketones undergo chemoselective alpha-monobromination with excellent yields at 0-5 degrees C or room temperature. The notable advantages of this protocol are no need of chromatographic separation, use of less hazardous reagent than molecular bromine, and no added base, Lewis acid, or other catalyst.
ABSTRACT
Regioselective synthesis of novel steroidal anti-inflammatory ante drug analogues, viz., [16alpha,17alpha-d]-isoxazolines 1(a-h) and 2(a-h) prepared in a single step in good yield by the reaction of 16-dehydropregnenolone acetate (16-DPA) 1 or related 21-chloro-20-oxopregnane 2 with various aldoximes (a-h) in presence of chloramine-T in refluxing ethanol.
