Patent GB-849558-A (GB)
Title: Hydroxy-pregnanes and process for their manufacture
IPC: C12P33/00
Filed: 1956-09-24
Abstract: The invention comprises \se4 and \se1,4 unsaturated 14a -hydroxy-pregnanes which are oxygenated in at least the 18- or in the 11- and 18- positions, their functional derivatives, e.g., ketals, acetals, ethers, esters, thioesters, thioethers, lactones, mercaptals, enol esters, enol ethers, enamines, hydrazones and semicarbazones, and a process for their preparation by oxygenation of the corresponding 14-H compounds by action under aerobic conditions of enzymes of fungi of genera Mucor, Helicostylum, Pleospora or Curvularia with subsequent conversion to functional derivatives if required.  The compounds may be additionally substituted, e.g. by hydroxy, keto, epoxy or methyl groups or by halogen atoms in positions such as 2-, 4,- 5,- 6,- 7,- 8-, 9-, 12-, 15-, 16-, 17- or 21-, and may be of any steric configuration.  Specified products include 14a -, 18-dihydroxy- and 14a -hydroxy-18-oxo-progesterone, 14a , 17a , 18-trihydroxy- and 14a , 17a -dihydroxy-18-oxoprogesterone, 14a -, 18-dihydroxy- and 14a -hydroxy-18-oxo-cortexone, 14a , 17a , 18-trihydroxy and 14a , 17a -dihydroxy-18-oxo-cortexone, 14a , 18-dihydroxy-corticosterone and -11-dehydro-corticosterone, 11-epi- 14a -, 18-dihydroxy- and 11-epi-14a -hydroxy-18-oxo-corticosterone, 14a , 17a -dihydroxy-aldosterone, 14a , 18-dihydroxy-hydrocortisone, 14a , 18-dihydroxy- and 14a -hydroxy-18-oxo-cortisone, the corresponding 1-dehydro-and 21-oxo compounds, also corresponding functional derivatives, e.g. 9a - or 12a - halo compounds; particularly 14a , 18-dihydroxy-9a -fluoro-corticosterone and -1-dehydrocorticosterone, and 14a -hydroxy-9a -fluoro-aldosterone and -1-dehydroaldosterone. Ester or enol ester groups present may be derived from any organic or inorganic acid including, formic, acetic, chloracetic, trifluoracetic, propionic, butyric, valeric, trimethylacetic, diethylacetic, caproic, oenanthic, caprylic, palmitic, crotonic, undecanic, undecylenic, oxalic, succinic, pimelic, maleic, lactic, carbamic, alkoxycarboxylic, b -cyclopentylpropionic, hexahydrobenzoic, benzoic, phenylacetic, cyclohexylacetic, phenylpropionic, trimethylgallic, phthalic, furane -2-carboxylic, isonicotinic, methane sulphonic, p-toluene sulphonic, sulphuric, hydrohalic, and phosphoric acids, while specified ether groups are tetrahydropyranyl, benzyl, and triphenylmethyl.  In examples: (1) aldosterone in acetone is treated for four days at 28 DEG  C. with a culture of Pleospora gaeumanni or Curvularia pallascens and 14a -hydroxyaldosterone isolated by extraction with ethyl acetate and paper chromatography using propylene glycol-toluene; subsequent treatment with acetic anhydride-pyridine yields the 18, 21-diacetate; (2) 1-dehydroaldosterone is treated with Pleospora gaeumanni as in (1) to give 1-dehydro-14a -hydroxy-aldosterone and then its 18, 21-diacetate; (3) the (18-->11b )-lactoneof-\se4-3,20-dioxo-11b -hydroxypregnene 18-acid is treated as in (2) to yield the lactone of-\se4-3,20-dioxo-11b , 14a -dihydroxypregnene 18-acid; (4) and (5) as in (1) aldosterone is incubated with Mucor griseocyanus, Mucor parasiticus or Helicostylum piriforme to give 14a -hydroxyaldosterone.  Specifications 821,777 and 825,210 are referred to.