COMMUNICATIONS TO THE EDITOR
38.56
STEROIDAL SAPOGENINS, 173. 16-DEHYDROPREGNEN-5-0Lc3-DIONE-12,20 FROM RICOGENIN, A NEW STEROIDAL SAPOGENIN h%:
extensive search for naturally occurring steroidal sapogenins having substituents in ring C which may be utilized for the synthesis of cortisone, the anti-arthritic hormone, a new saponide, riconin, m.p. 285-289' dec., was isolated from the mixture of glycosides occurring in Dioscorea 11Itzcrostachyn. In
ail
c o
H
UJ
d
16-Dehydropregnen-5-01-3-dione-l2,20
Vol. 71
Calcd. for C;*HseOh: C, 74.8; H, 8.2. Found: C, 74.0;
H, 81.
BOTANICA-MEX, S. A. PLAZA DE SAN PABLO NO. 6
RUSSELLE. MARKER TEXCOCO, MEXICO HOTELGENEVE,MEXICOCITY RECEIVED OCTOBER 4, 1949
ALLO-PREGNAN-3,12,2O-TRIONE
Sir : The current interest in Kendall's substance E for rheumatoid arthritis has stimulated great in-
C
C
/JJJ
HO
Pseudobotogenin
Hydrolysis of riconin with alcoholic hydrochloric acid terest in the search for starting materials for its gave ricogenin, m.p. 225-227'. Anal. Calcd. for C~Hlo06: synthesis. Recently, Marker reported the possiC , 72,9; H, 9.1. Found: C, 72.9; H, 9.1. Ricogenin formed a diacetate, m.p. 195-197', and con- bility of utilizing a steroidal sapogenin, botogenin, tains three ketonic groups having the same side-chain isolated from Dioscorea Mexicana. Its degradastructure as kryptogenin. Anal. Calcd. for C3iH~01: tion product was 5-pregnen-3(p)-01-12,20-dione, C, 70.4; H, 8.1. Found: C, 70.2; H, 8.2. characterized by conversion to allo-pregnan-3,12,Treatment of ricogenin with acetic anhydride a t 195' for 20-trione) m.p. 264'. The latter was identical eight hours followed by hydrolysis gave pseudoricogenin, from the degram.p. 220-222'. Anal. Calcd. for CnH3804: C, 76.0; H, with allo-pregnan-3,12,20-trione2 9.0. Found: C,76.2; H,9.O. dation of hecogenin. When heated with alcoholic hydrochloric acid for fifteen We have prepared an authentic sample of allo-pregnanminutes, pseudoricogenin was converted into ricogenin, by a n entirely different route and have found m.p. and mixed m.p. 225-227'. Catalytic reduction of the 3,12,20-trione completely different from the trione from hecogenin. diacetate of pseudoricogenin, using palladium-on-barium it Desoxycholic acid has been degraded to 12(a)-acetoxyprosulfate as catalyst, saturated only the conjugated double gesterone (I), m.p. 181°, [ C Y ] ~ D +215", [(Y]%oI +269" bond in ring D, giving the diacetate of pseudobotogenin. (chloroform), absorption maximum at 240mp(log e 4.14 in This product upon alkaline hydrolysis followed by iso- ethanol) . 3 This compound (I) upon sodiumalcohol reducmerization with alcoholic hydrochloric acid gave botogenin, followed by chromic acid oxidation furnished allom.p. and mixed m.p. 260-262O.s Anal. Calcd. for Cd&oO4: tion pregnan-3,12,20-trione (11). m.p. 206-208', [(Y]*~D +184", Ci75.7; H, 9.4. Found: C, 75.5; H, 9.4. [ 0 1 ] +224O ~ ~ ~ ~ (chloroform), ~ nomaximum a t 240mp. Anal. Acetylation of this product gave botogenin acetate, Calcd. for CzlH3oOs: C, 76.3; H, 9.2. Found: C, 76.0; H, m.p. and mixed m.p. 246-248". Anal. Calcd. for 8.9. The reduction was also accomplished with hydrogen '&Hd205: C, 74.0; H, 9.0. Found: C, 74.1; H, 9.3. and Adams catalyst in acetic acid; subsequent hydrolysis The pseudobotogenin diacetate produced by the catalytic and oxidation gave the same product (11). The course of reduction of the diacetate of pseudoricogenin was oxidized these methods of reduction has been shown previously' with chromic anhydride in acetic acid, followed by hydrolysis,' giving 16-dehgdropregnen-5-ol-~-di0ne-12,20 (1) Marker, THISJOUXNAL, 71, 3656 (1949). (2) Marker, Wagner and co-workers, ibid., 69, 2167 (1947). acetate, m.p. and mixed m.p. with the product Hepared (3) Shoppce nnd Reichstein, RcZv. Ckim. Acre, 94, 361 (1941). from naturally occurring botagenin, 22S-2P7°, Anal. (1) Mcrker, T&d I@wWnnz,V i r $@$Q &?4'a)a
(4) Mnrker and Wittlc, Tme JOIJERA~, 89, 2704 (1987); Butennndt rod Weischer, Baed M, 4094 (1086),
COMM~JNICATIONS TO THE EDITOR
Nov., 1949 CH3 AcO
CHa
I
C=O
0
I
c=o
1. Na-Alcohol ______, 2. CrOa-HOAc ,
I1
1 2 ( 4-Acetoxyprogesterone
allo-Pregnan3,12,20-trione
CH3 I
HO
C=O
0
12(a)-Hydroxypregnan3,20-dione
CH3 I
)yYc=o ) 0
Pregnan3,12,20-trione
3857
powerful analgesic surpassing morphine in clinical tests2. 1,2,7-Trimethoxynaphthalene,m.p. 38.5-39.5 ', b.p. 133' a t 1 mm. (picrate3, m.p. 113')) gave by reduction* with sodium and alcohol, the crystalline ketone, m.p. 76' (anal. calcd. for CloHgO(OCH&: OCH,, 30.1. Found: OCH3, 29.5, 29.3) , characterized as the semicarbazone, m.p. 191-191.5', and the 2,4-dinitrophenylhydrazonej m.p. 167' dec. (anal. calcd. for C18H1808N4: C, 56.0; H, 4.7; N, 14.5. Found: C, 55.7; H, 4.6; N, 15.0, 14.8). The structure of the ketone was shown by oxidation, with alkaline permanganate, to hemipinic acid, identified by its m.p.6 (177179') and by the m.p.6 (166-167') and characteristic fluorescences of the pure anhydride. 2,7-Dimethoxynaphthalenesimilarly4 gave on reduction 7-methoxy-2-tetralone, m.p. 27-28', b.p. 124-126' (1.5 mm.); semicarbazone, m.p. 174-176' (anal. calcd. for C12H1,O2N3: C, 61.8; H, 6.5. Found: C, 62.1, 62.1; H, 6.4, 6.4); 2,4-dinitrophenylhydrazonem.p. 177-181' (anal. calcd. for C17H16N406: C, 57.3; H, 4.5. Found: C, 57.2, 57.5; H, 4.4, 4.6).
to lead t o the allo-configuration a t C-5. Nevertheless, we (2) Schnider and Grussner, Helw. Chim. Acta, 81, 821 (1939). have prepared the corresponding isomer, pregnan-3,12,20(3) Chakravarti and Pasupati, J . Chem. SOL.,1859 (1937). trione (IV), by the mild oxidation of an authentic sample of (4) Cornforth, Cornforth and Robinson, ibid., 689 (1942). 12(c~)-hydroxypregnan-3,20-dione (111). It had the follow( 5 ) Perkin, ibid., 109, 922 (1916). ingproperties: rn.p.204-206', [ ~ ] S +181", D [cY]~ +225O ~u~~ (6) Dobbie and Lauder, ibid., 6'7, 19 (1895). (chloroform). AnaE. Calcd. for CllH3003: C, 76.3; H. OF CHEMISTRY MILTOND. SOFFER 9.2. Found: C, 76.0; H, 9.1. Reichstein and von ArxS DEPARTMENT COLLEGE J. CHARLES CAVAGNOL report for pregnan-3,12,20-trione: m.p. 201-202'; [ ( Y ] ~ ~SMITH D MASS. HILDAE. GELLERSON +182 * 7, [ C Y ] ~ ~ M B I+219 * 8 (ethanol). A mixture of IV NORTHAMPTON, The with I1 showed a melting point depression of 36'. RECEIVEDOCTOBER 19, 1949 melting point of each of these compounds was depressed 10-20" by the ~ i o n from e hecogenin. Since the properties of elZo-pregnan-3,12,2O-trione(11) DEGRADATION OF GLYCOGEN TO ISOMALTOSE are different from those of the samples derived from hecogenin and botogenin, some doubt must be entertained as to Sir: the structures of the degradation products from both of Methylation studies' have indicated that the these sapogenins. glycogen molecule has a highly ramified structure We thank Parke, Davis and Company for their help.
composed of a-D-glucopyranosyl units joined 1,4 with branching a t C6 on one out of twelve units. As additional evidence in support of this structure THEWHITMORE LABORATORIES R. B. WAGNER we report the isolation of crystalline 6-a-~-glucoSCHOOL OF CHEMISTRY A N D PHYSICS THEPENNSYLVANIA STATE COLLEGE JAMBS A. MOORE pyranosyl-P-D-glucopyranose octaacetate (P-D-iS0F. FORKER PBNNSYLVANIAROBERT STATECOLLEGE, maltose octaacetate) from an acetylated acid RECEIVED OCTOBER 10, 1949 hydrolysate of glycogen. Animal (rabbit liver) glycogen (5.00 g., [aylz6~ SYNTHESES IN THE DIRECTION OF MORPHINE. I. +200', c 0.92, water) in 2% concentration was 7-METHOXY- AND 7,8-DIMETHOXY-2-TETRALONE. hydrolyzed a t 100' in 0.05 N sulfuric acid for nine hours (degree of hydrolysis ca. 75%). After acid Sir : We wish to report the synthesis of 7,s-dimeth- neutralization with barium carbonate and ion reoxy-2-tetralone, which may serve as a useful moval with exchange resins (Amberlite IR-100 and intermediate for elaboration in the direction of IR-4))the amorphous solid obtained on solvent remorphine and certain of its degradation products,' moval was acetylated with hot acetic anhydride and may open a way for the preparation of physi- and sodium acetate. The resultant sugar acetate ologically active substances oxygenated a t points mixture (6.08 g.) was chromatographed2 on Magcorresponding t o the 3 and 4 positions in mor- nesol-Celite under such developmental conditions phine. 7-Methoxy-2-tetralone may serve in the that monosaccharides were removed from the syntheses of substances similarly substituted in column. P-D-Glucose pentaacetate was identified, (1) W. N. Haworth and E. G. W. Percival, J . Chem. SOC.,2277 the 3 position; and is of particular interest in view W. N. Haworth, E. L. Hirst and F. Smith, ibid., 1914 of the recent report that 3-hydroxymorphinane is a (1931); (1939). (5) Reichstein and von Arx, Xclu. Chim. Acto, 98, 747 (1940).
(1) F i c m and Holmes, THIOJOURNAL, W, 2549 (1088); 60, 2a19
~ i ~ a oc.L~, ) ; J . cim. SOC., aaw (ioaa.
(2) M.L. Wolfrom, L. W. George8 and I, L. Miller, THIO Joumhr. IO. 47s (iom; T I , la6 (1949~
