Патент USA US2408833код для вставки
Patented Oct. 8, 1946 ' 7 , UNITED" STATES PATENT} OFFICEy rsnvnoknyrroennm AND ITS DIACETATE Romeo B. Wagner, State College, Pa., assig'nor to Parke, Davis & Company, Detroit, Mich., a cor-'- ' poration of Michigan - - - No Drawing. Application May 15, 1944, Serial No. 535,756 4 Claims. (Cl. 260-2395) This invention relates to the preparation of new pseudo-sapogenins from certain steroidal sapogenins which are described in J. Am. Chem. Soc. 65, 1199 (1943). These compounds are valuable as intermediates for the preparation of 5" hormonesv of the sex hormone type and particularly of the adrenal cortex hormone type since they are oxygenated at position 12 of the steroid nucleus. The reaction by which steroidal sapogenins are 10' in a sealed tube for 10 hours. The solvent is removed in vacuo and the residue hydrolyzed with excess potassium bicarbonate (or alcoholic potash) in aqueous ethanol. The product is ether extracted, crystallized from acetone and then re crystallized from ether to give pseudokryptogenin, M. P. 189—192‘’ C. A mixture of this product with kryptogenin melts at 162—167° C, AnaL:C,Calc’d. for9.8%. C27H40O3: C, 78.6; H, 9.8%. Found: 78.5; H, isomerized to the pseudo-genins have been described in detail in the copending Patents Nos. 2,352,848 and 2,352,852, issued July 4, 1944. These Treatment of pseudo-kryptogenin with hot ethanolic hydrochloric acid converts it back into kryptogenin. The pseudo-kryptogenin of this also include proof of structure of the pseudogenin side chain. examplehas the formula, 15 . _ This invention relates to the preparation of 0H: pseudo-genin compounds having the formula, 0H: ' on, (gon 0 CH dB = — 3- ' ' a ; HY ' " 20 __ H . - I where Y and Y' are-918mm“ °f the glass 5' ‘ I ‘I; Pseudo-kryptogenin 25 Pseudolcryptogenin ‘(from pennogem'n) I of anhydride 6 grams ofispennogenin acetate in 18Acc.mixture of acetic heated at 200° 0. for _ v: 10 hours. <11 The mixture is evaporated in vacuo ‘30 on the steam bath and then re-evaporated with -» > ethanol to remove the remaining acetic anhy dride. Afterwith decolorizing methanolbrand)‘, solutionthe of the residue charcoal a(“Norite” mid gm?“ hydrolyzable to 0H HzOH _V I . 0H ’ ‘ éH-OH: ‘_ OH ’ H- Q ‘ ‘ _c ‘ 3 __l pl , 011,011, _ 3 on. _ CH, ‘ , ‘ product is crystallized from methanol and has 35 M. P. 68-73° C.v It is further puri?ed by hy H I have found that three sapogenins, Penno- ‘drolysis with 5% ethanolic potash and crystalli , - to give a_ zation from ether and then methanol genin,‘ n'olog'enin and kryptogenin (see J. Am. _~ gigggggeggnn?'fribg?gglgied M' P'_Wlth pseudo. Chem. Soc., 65 1199~,~~1943),_when treated under . .~ . ' . . ' - the conditions described in Patents Nos. 2,352,848 4“ FoAunnglf'ccggcgd%€ogcg7go§" C’ -7§'6,%’ H’ 93%‘ and 2352 852 for isomerizing to pseudo-genins, ' . ’ ' . .’ ’ ' ' I I ’ ’ . . are pseudo-kryptogenin. converted into the same pseudo-genm, name‘1y, The diacetate prepared, re?uxing krypbogenin withis.acetic a. 1 by ydride, and pseudo. crystaL from“ to‘ give material of M; ,P. T.“ inventifn' may be illustrated by the ml‘ 45 lized 120-125“ '0.‘methanol ‘Recrystallization ‘from methanol 1°Wmg exam!’ esgives material of M. P. 115-125 and 124-126° c. pseudokrw togenin ( fTom hrw to 9enin) H,AnaL: 9.2%. Found: Calc’d 0, for72.5; C31H4405-CH3OH: H, 8.6%. C, Asolution of 5 grams of kryptogenin diacetate In a second run, the product from 20 g. of m 15 cc. of acetic anhydride is heated at 200° C. 50 pennogenin acetate and 25 cc. of acetic anhydride 2,408,832 3 NaOH, K2003, KHCO3, NazcOs, NaHCOa or the like. If an alcohol is required to aid hydrolysis, is hydrolyzed directly and then crystallized from acetone to give 11 g. of pseudokryptogenin. this can be methanol or other lower aliphatic The transformations of this example may be illustrated as follows: on ’ alcohol instead of ethanol. What I claim is: 1. Compounds having the formula, oH-oH. CH; CH1 I CH: C=C--CHz-CH1 A *‘ 13-011, 10 ‘ CHY . Pennogenin acetate ‘Pl/o where Y and Y’ are members of the class con A020 lat 200° 0. sisting of ' on CHsCHg on a on i CH‘ ‘/ v H~CH| HPO A0 20 H and groups hydrolyzable to OH 25 Hydrolysis (alcoholic KOH) AcO 2. Compounds having the formula. CH: Pscudo-kryptogenin,diacetate. CH" CH: CH1 C/ /\ all? who l omen CH‘ t ._——= c r: onr on3 30 \ (‘m-on, __.__ oaY N Y’ 35 where Y and Y’ are members of the class con sisting of on Pseudorkryptogenin Pseudokryptogenm (from noloyem'n) 40 This example is carried out under the same conditions as the other examples but starting with nologenin diacetate which has the formula, CH1 H and organic carboxylic acid ester groups hydro lyzable to 45 OH ‘ HO . H CH: 3. Pseudokryptogenin having the formula, \bnl ' 50 CH:ACH: EH’ /CH,CHI =0 H-om -_\ lkcoi/ \J 55 HIOH \/" Nologenin diac‘etats The same products, pseudokryptogenin and its HO 4. Pseudokryptogenin diacetate having the the preferred isomerizing agent is acetic anhy 60 formula, CH; CHzCHs dride, other lower aliphatic acid anhydrides may on, on, a =C / H-CHl also be used. The preferred temperature range diacetate are obtained. ' While for'ease of manipulation and economy ‘ lies between 190° and 200° C. although 'thefreac tion also takes place as low as 170° or as high as 230"‘. The example is intended as illustrative and the invention is not necessarily limited to “5 the conditions and reactants therein cited. In addition to using ethanolic KOH solution kaline solution, for example one containing \f“ A00 for hydrolyzing the acylated pseudogenin to the free genin, one can use any other suitable al HIOAO 70 ROMEO B. WAGNER.