Patent Publication Number: US-3875193-A

Title: Preparation of hydroxylated steroids

Description:
United States Patent Mazur et al. Apr. 1, 1975 [5 PREPARATION OF HYDROXYLATED 3.325.484 6/l967 Deghenghi 4. zen/239.55 STEROIDS 3,7085 ll l/l973 VanVliet et al .r 260/3975 [75] Inventors: Yehuda Mazur, Tel-Aviv; Avner Rmman Rehovot! both of Israel Primary Examiner-Henry A. French 73 Assignee; Yeda Research and Devdopmem Attorney, Agent, or FirmHubbell, Cohen Stiefel Co., Ltd., Rehovot, lsrael [22] Filed: Apr. 5, 1973 211 Appl. No.: 348,229 [571 ABSTRACT A process for preparing l4B-hydroxy derivatives of [30] Forelg Apphcauo&#34; Pnomy Dam saturated steroid compounds which comprises dis- Apr 9. 1972 Israel 39165 solving the starting material in a suitable solvent together with peracetic acid and heating the reaction Cl 9 60/3975 mixture or irradiating it under ultraviolet light at a [5 l 1 Int. Cl. C07c 169/48 wavelength below 350 my and separating the desired Fleld Search Searched Steroids product from the reaction mixture. The invention also relates to certain new l4B-hydroxy derivatives of androstane. [56] References Cited UNITED STATES PATENTS 1 Chum! 1 Drawing Figure 3.l83,253 5/1965 Klimstra 260/3975 PATENTEDAPR H975 OAc OAc  
 COOCHB COOCHg OAc OAc  
 OAc  
 PREPARATION OF HYDROXYLATED STEROIDS BACKGROUND OF THE INVENTION Processes for the introduction of 14B-hydroxy groups into steroids are known; see for example Chem. in Britain, l, (1965) 454. The known processes are rather complicated, and involve a number of steps. The known processes have not attained any practical importance. The novel process according to the present invention is a simple one-step process.  
 SUMMARY OF THE INVENTION The invention relates to a process for producing 143- hydroxylated steroids, comprising dissolving a saturated steroid in a suitable solvent together with pcracetic acid and subjecting the reaction mixture to heating or to u.v. irradiation at less than 350 mu.  
  For example, irradiation of androstane-17-acetate or of adrostane-3,l7-diacetate dissolved with peracetic acid in tertbutanol, results in the formation of the respective 14Bhydroxy and Sa-hydroxy derivatives, which are separated by conventional methods.  
  In a similar manner, heating or irradiation of 3 acetoxy aethiocholanic acid results in the corresponding 14,8-hydroxy derivative. This is easily converted to cardenolide and bufetenolide derivatives in a few simple conventional steps.  
  Some of the compounds obtained by the process according to the present invention are novel compounds, and as such form part of the invention.  
  In the following the novel process according to the present invention is exemplified with reference to some saturated steroids, and it is to be understood that these are illustrative only and are to be construed in a nonlimitativc manner.  
 EXAMPLE 1 A solution was prepared which consisted of l.5g of androstane 3B.l7B-diacetate, 20 ml. of 15% peracetic acid (in acetic acid) and 100 ml. of tertbutanol. This solution was irradiated for five and a half hours with u.v. of a wavelength of less than 350 mg.  
  The resulting solution was subjected to chromatography on silica gel and eluted with ethyl acetate/benzene. 1n addition to the starting material there was obtained a quantity of 150 mg. of the novel l4B-hydroxy derivative, mp 156C, 11.6 and 130 mg. of the known corresponding Sa-hydroxy derivative mp EXAMPLE 2 10 ml. of a solution of 40 percent peracetic acid in ethyl acetate were added dropwise over 12 hours to a solution of 1.5 g androstane-flBJ 7B-diacetate in l() ml. ethyl acetate. while under reflux.  
  At the end ofthis period of time the reaction mixture were worked up as in Example 1. There was obtained 450 mg. of the novel l4B-hydroxy derivative, M.P. 156C and 355 mg. of the Sa-hydroxy derivative, M.P. l79-180C.  
 EXAMPLE 3 A quantity of l g of aethiocholanic acid methyl ester 3-aeetate were dissolved in 25 ml. ethyl acetate, there was added 3 ml. of 707: peracetic acid in acetic acid. and the reaction mixture was subjected for 4 /2 hours to u.v. from a lamp emitting at ca. 300 m After chromatography on silica gel and elution with ether:hexane the corresponding I4B-hydroxy derivative was isolated in a 10% yield, m.p. 194-|95C, identical with the known derivative.  
 EXAMPLE 4 A solution of 2.4 g. androstane-l7B-acctate in ml. of t-butanol and 30 ml. peracetic acid 15% (in acetic acid) was irradiated for 14 hours with u.v. light of 300 nm wavelength.  
  The reaction mixture was diluted with ether, washed consecutively with aqueous sodium bisulfite, sodium bicarbonate and water. The ether extract was evaporated to dryness.  
  Chromatography on silica gel gave 270 mg. of the known 17B-acetoxy-5a-hydroxy androstanc, mp. 146C and 270 mg. of l7B-acetoxy-l4B-bydroxy-5a hydroxy-androstane, m.p. I l35l3o&#34;Cv We claim:  
  I. A process for preparing the l4B-hydroxy derivative of aethiocholanic acid methyl cstcr-3-aeetate which comprises dissolving aethiocholanic acid methyl ester-3-acetate in a suitable solvent therefor together with peracetic acid to form a reaction mixture. subjecting the reaction mixture to heating or irradiation with ultraviolet light having a wavelength below 350 mp, and separating the desired l4B-hydroxy derivative from the reaction mixture.