Patent GB-877585-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J75/00
Filed: 1958-05-21
Abstract: The invention comprises steroid compounds of the general formulae <FORM:0877585/IV (b)/1> wherein the lower alkyl group contains 1 to 8 carbon atoms and R p  represents hydrogen or the acyl group of a carboxylic acid, and the preparation thereof by reacting pregnane-3,11,20-trione 3,20-bis(ethylene acetal) with the required lower alkyl lithium to form an 11b -hydroxy-11a -lower alkyl-pregnane-3,20-dione 3,20-bis(ethylene acetal), hydrolysing this compound with acid to form 11b -hydroxy-11a -lower alkyl-pregnane-3,20-dione halogenating e.g. with t-butyl hypochlorite or N-bromosuccinimide, and then dehydrohalogenating the resulting 4-halo-11b -hydroxy-11a -alkylpregnane-3,20-dione to form 11b -hydroxy-11a -alkyl-4-pregnene-3,20-dione of the second formula, diglyoxylating this compound in the 2- and 21-positions to form 2,21-dialkoxyoxalyl-11b -hydroxy-11a -alkyl-3,20-dione, monoiodinating this compound to form 2,21-dialkoxy-oxalyl-11b -hydroxy-11a -alkyl-21-iodo-4-pregnene-3, 20-dione, treating this compound with the required alkali metal acylate to form 2 - alkoxy-oxalyl-11b ,21-dihydroxy-11a -alkyl-4-pregnene-3,20-dione 21-acylate, brominating this compound to form 2-bromo-2-alkoxy-oxalyl - 11b ,21 - dihydroxy-11a -methyl-4-pregnene-3,20-dione 21-acylate, treating this compound with a base 2-bromo-11b ,21-dihydroxy11a  - alkyl - 4 - pregnene-3,20-dione 21-acylate, treating this compound with zinc and acetic acid to form 11b ,21-dihydroxy-11a -alkyl-4-pregnene-3,20-dione 21-acylate and, if desired, hydrolysing this compound to the corresponding 21-hydroxy compound both of the third formula above, or hydrogenating the 11b ,21-dihydroxy-11a -alkyl-4-pregnene-3,20-dione 21-acylate or the corresponding free 21-hydroxy compound e.g. in the presence of palladium catalyst, to form a compound of the first formula above and, if desired, hydrolysing the 21-acylate to the corresponding 21-hydroxy compound; (b) by reducing an 11a -alkyl-pregnane-3,20-dione with sodium borohydride to form 3,11b -dihydroxy-11a -alkyl-pregnane-3, 20-dione, monobrominating this compound to form 3,11b  - dihydroxy - 11a  - alkyl-21-bromo-pregnane-3,20-dione, reacting this compound with the required potassium acylate to produce a 3,11b ,21-trihydroxy-11a -alkyl-pregnane3,20-dione 21-acylate, oxidising this compound with chromic acid to form the desired 11b ,21-dihydroxy-11a -alkyl-pregnane-3,20-dione 21-acylate, and then, if desired, hydrolysing this compound to the desired 21-hydroxy compound both of the first formula above; and (c) by monoglyoxylating an 11b -hydroxy-11a -alkyl-4-pregnene-3,20 -dione to form the 21-alkoxyoxalyl - 11b  - hydroxy-11a -alkyl-4-pregnene-3,20-dione and then brominating and acylating to form an 11b ,21-dihydroxy-11a -alkyl-4-pregnene-3, 20-dione 21-acylate of the third formula above, and then hydrogenating and, if desired, hydrolysing as under reaction (a) above.  Detailed examples are given.  In addition, the Specification includes a list of carboxylic acids from which the 21-acyloxy groups may be derived. Specifications 723,189, 738,311, 738,580, 743,484, 775,411, 829,476 and 873,695 and referred to.