July 20, 1954
COMMUNICATIONS TO THE EDITOR
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all have the D-configuration a t C-25 while sarsasapogenin has the L-configuration. The configuration a t C-22 (spiroketal) together with previous correlat i o n ~ * .of~ infrared absorption with side-chain structure therefore comes into question. We have converted pseudodiosgenine [m.p. 165-168’, [alZ5jo-39’ (170 in chf.); found: C , 78.26; H, 9.91; medium band in infraredg a t 1693 ern.-' (lye in chf.)] into neodiosgeninZb [m.p. 197-201°, [ a ] D -122’ (1% in chf.); found: C, 77.77; H, 9.84; shoulder in infrared a t 982 cm.-l, strong bands a t 960, 920, 896 cm.-l, weak bands (9) P. Reichard and U. Lagerkvist, A d a Chem. Scand., 7, 1207 a t 856 and 973 cm.-l (l$&in CSZ),S9G cm.-‘ band (1953). more intense than 920 cm.-l band. Mixture DIVISIONO F NUTRITION AND PHYSIOLOGY melting point with diosgenin (m.p. 208-211’), THEPUBLIC HEALTH RESEARCH INSTITUTE L. H. SMITH, JR. m.p. 191-192.5’1 by very mild treatment with STETTEN, JR. OF THE CITYOF NEWY o u , INC. DEWITT XEWYORK,N. U. acid. Upon more vigorous acid treatment, neoRECEIVED JUNE 15, 1954 diosgenin yielded diosgenin4 [m.p. 206-21 lo, no depression mixed with an authentic specimen, strong bands in infrared a t 982, 963, 921 and 900 THE STEREOCHEMISTRY OF STEROIDAL cm.-l, weak band a t 860 cm.-’; 982 cm.-’ band SAPOGENINS more intense than 963 cm.-’ band, 900 cm.-’ Sir: band more intense than 921 cm.-’ band]. Despite the voluminous literature’ dealing with Consideration of the probable mechanism of the structure and chemistry of the steroidal sapo- conversion of pseudodiosgenin to neodiosgenin and genins, the stereochemistry of the spiroketal side this to diosgenin leads to the assignment of strucchain of these substances remains obscure. In ture I1 to neodiosgenin and structure 111 to dioslight of recent discoveries this appears to have been genin. These acid-catalyzed reactions are condue in large part to the failure to appreciate the ceived to be polar in nature, with trans addition importance of the asymmetry a t both the C-22 occurring across the C-20,C-22 double bond.’O and C-25 positions. The fact that certain of these In the initial cyclization of pseudodiosgenin to substances can be converted2 by rather vigorous neodiosgenin, it would appear that attack of a acid treatment into isomeric substances, together solvated proton a t C-20 froin the less hindered with other lines of e ~ i d e n c ehas , ~ led to the assump- rear face of the molecule is kinetically favored and tion3 that such naturally occurring stereoisomeric leads to structure 11. However, on prolonged pairs of steroidal sapogenins as sarsasapogenin and treatment with acid a process of equilibration smilagenin are epimeric a t C-22. Recent ~ t u d i e s ~leads , ~ to the thermodynaniically more stable strucof infrared absorption have shown that the spectra ture 111; the driving force for the conversion of of all naturally occurring steroidal sapogenins neodiosgenin (11) to diosgenin (111) is furnished thus far examined possess bands in the vicinity of by hindrance between the C-18 methyl groups 9S0, 920, 900 and S60 cm.-’, which are character- and C-21 and possibly by the less stable axial istic of the spiroketal side chain. The relative conformation11~’2of the C-27 methyl group in intensities of the 920 and 900 cm.-l bands have been structure 11. The initial forination of the kineticcorrelated with the so-called “normal” and (‘iso” ally favored but thermodynamically less stable series, which were assumed to be epimeric a t C-22. neodiosgenin (11) and its subsequent double inHowever, recent work6 involving careful repetition version a t C-20 and C-22 to the more stable diosof s3me earlier transformations together with genin (111) is analogous to the formation of cholesdegradation studies has demonstrated that sarsa- terol h,Bp-dibromide and its isomerization to the sapogenin and smilagenin are epimeric a t C-25 more stable 5R,Ba-dibr0mide.‘~ and does not exclude the possibility that these I t will be noted that the relative intensities of the substances actually have the same configuration infrared bands near 900 cm.-’ and 920 cm.-’ are of a t C-22. By means of similar degradation of ( 8 ) (a) R. E. Marker, T. Tsukamoto and D. L. Turner, THIS diosgenin and hecogenin and by correlation of side JOURNAL, 60, 2525 (1940). (b) D. H. Gould, H. Staeudle and E. B. chain degradation products with the absolute Hershberg, ibid., 74, 3685 (1952). (9) A. L. Hayden, P. B. Smelzer and I. Scheer, Anal. Chem., 06, configuration of D-glyceraldehyde, James’ has (1954). shown that diosgenin, hecogenin and smilagenin 550(10) The C-20,C-22 double bond of pseudodiosgenin requires the
servations of Reichard,g and together with these, delineate the probable pathway of orotic acid synthesis in the rat: citrulline f aspartate (arginosuccinate) -+ ureidosuccinate (dihydroorotate) orotic acid. Neither in rat nor in pigeon liver slices (Table I) cnuld any contribution to orotic acid from the ainidine carbon of arginine be detected. The pxtulated intermediate arginosuccinate would therefore appear not to arise from arginine in the preparations studied.
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(1) See L. F. Fieser and RI. Fieser, “Natural Products Related t o Phenanthrene,” 3rd ed., Reinhold Publ. Corp., New York, N. Y., 1949, Chapt. VIII. ( 2 ) See, for example: (a) R . E . Xfarker and E. Rohrmann, THIS 61, 816 (1939); (b) R. E. Marker and J. Lopez, ibid., 69, JOURNAL. 2373 (1947). (3) See ref. 1 , pp. 587, 589. (4) C. R. E d d y , M. E . Wall and M. K. Scott, Anal. Chent., 06, 286 (1953). ( 5 ) R . N. J O I W , E. Katzenellenbogen and K. Dobriner. ibid., 76, 158 (1953). (fi) 1. Scheer, R. B Kostic and E. Mosettig, i b i d . , 7 5 , 4871 ( I Y i 3 ) ( 7 ) V H. T . James, Chemistry and Industry, 1388 (1953).
cis fusion of rings D and E on steric grounds, presumably in the 8configuration. (11) T h e axial conlormation of the C-27 methyl group coincides with hindrance between the C-18 and C-21 methyl groups oniy il the absolute configuration of the steroid-nucleus is as drawn; cases I1 and I11 would then represent absolute configurations of neodiosgenin and diosgenin, respectively. If the absolute configuration of the steroid nucleus is actually the mirror image of its usual representation, neodiosgenin (11) would differ from the above structure in possessing an equatorial methyl group a t C-25, and diosgeuin (111) would then have the axial tnrttiyl group a t C-25. (12) D. H . I-,Guelph, Ontario, and H. L. HOLMES,The Carwin Company, North Haven, Connecticut (Editors). Acatleinic Press, Inc., 125 East 23rd Street, S e w York 10, S . Y. 1953. viii 422 pp. 16 X 23.5 cm. Price, ~11.00. The third volume of the Manske and Holmes treatise on The Alkaloids has now appeared and continues to meet the Game high standards set by the earlier volumes. Again the editors have succeeded in assembling a group of reviews by especially well-qualified authors. Chapters on the cinchona alkaloids (Richard B. Turner and R . B . Woodward), quinoline alkaloids other than those of cinchona (H. T. Openshaw), quinazoline alkaloids (Openshaw), lupin alkaloids (Nelson J. Leonard), imidazole alkaloids ( A . R. Battersby and H. T. Openshaw), solanum and veratrum mall volume of only 125 pages! He deals with the practical author>, “It is intended primad), t u r the ubr of scicntifi(. ,)I- cxyrrimental side of the subject and he treats the modern
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