Dec. 20, 1957
COMMUNICATIONS TO THE EDITOR
6569
I n an alternate preparation of this diamine, a (And. Calcd. for CzaHaO: C, 84.00; H, 12.00. solution containing ethyl p - c y a n o b ~ t y r a t e(12 ~ g. ; Found: C, 83.35; H, 12.11). The infrared specb.p. 66' a t 1 mm., n z 5 1.4195)) ~ dimethylamine trum indicated absorptions a t all the wave lengths (16 g.) and ethanol (100 ml.) was heated in a bomb believed to be characteristic of a A7-stenolIs and tube a t 105' for 5 days. The N,N-dimethyl-fi- the rate of color development with the Liebermanncyanobutyramide (7.25 g., b.p. 77-78' a t 5 mm;. Burchard reagent was similar to that of A7-stenols.I nZ5D 1.4620) so prepared was reduced with excess The behavior of the acetate of the new sterol (11), lithium aluminum hydride (10 g.) in ether (600 m.p. 93-94') to hydrogenation in glacial acetic acid over Adams catalyst (no hydrogen uptake) was ml.). l-Amino-4-dimethylamino-2-methylbutane and (3 g., b.p. 106-108' a t 100 mm.) was i ~ o l a t e d . ~also characteristic of AI- and AE(g)-stenols,8 Its dioxalate (m.p. 175-176') was the same as that resulted in isomerization. The reaction product, of the diamine derived from the pyridazinium bro- m.p. 76-77', absorbed one mole of hydrogen upon mide (infrared spectra identical). forced hydrogenation in the presence of HC1 a t The ion (RzN=NH+) is probably the interme- 60°9 to yield a saturated sterol acetate, m.p. 99diate that reacts with the isoprene rather than the 101'. The alcohol, m.p. 153-155') resulting from neutral species (RZN +=N-) obtained when the reac- the hydrolysis of the acetate failed to respond to the tion mixture is neutralized. The above pyridazin- Liebermann-Burchard reagent, and its infrared ium salt was obtained (84% yield) directly from spectrum indicated the absence of double bonds. the acidic reaction mixture. When an acid solu- On Kuhn-Roth C-methyl determination, lo I1 liber0.27 equivalents of acetic acid (calcd. tion from oxidation of 1,l-dimethylhydrazine and ated 3.48 concentrated base were added simultaneously to a as 4-methyl-A'-cholestenyl acetate) or 3.60 f 0.26 solution of isoprene in methanol a t such rates that (calcd. as 4,4-dimethyl-Ai-cholestenyl acetate). the reaction mixture remained just basic to phenol- Synthetic 4,4-dimethylcholesteryl acetate," cholphthalein, tetramethyltetrazene (84% yield) was esteryl acetate and A7-cholestenylacetate gave 3.60 obtained. f 0.31, 2.90 f 0.03, and 3.00 f 0.22 equivalents Evidence that this intermediate reacts with ani- of acetic acid, respectively. Thus I1 possesses line, phenol, styrene and vinyl n-butyl ether has approximately one more C-methyl group than the been gained from experiments in which acid solu- Cz7 sterol acetates (C-methyl = cu. 0.6 mole of acetions of i t were mixed with each of these substances tic acid). From chemical and biogenetic considera(1-2 hour reaction times), and little or no tetra- tions, either 4(a or p)-methyl-A7-cholesten-3P-ol or methyltetrazene was found by spectroscopic analy- 4,4-dimethyl-A7-cholesten-3p-ol became attractive sis after the reaction mixtures were made basic. plausible structures for I. A7-Cholesten-3P-olwas The products here formed and further possible re- subjected to Oppenauer oxidation to give A7-choactions are under investigation. lesten-3-one, m.p. 143-145'. This ketone upon treatment with potassium, t-butyl alcohol, and (3) J. Bredt and J. Kallen, A n n . , 293, 351 (1896). methyl iodide, gave a mixture which was reduced (4) L. K. Amundsen and L. S. Nelson, THIS JOURNAL,73, 242 (1951). with LiA41H4. Purification of the resulting alcohols through the digitonides12 followed by silicic acid GEORGE HERBERT JONES LABORATORY UNIVERSITY OF CHICAGO W. H. URRY chromatography of the @-sterolsafforded two main CHICAGO 37, ILLINOIS compounds of m.p. 122-124' and m.p. 146-147', INORGANICCHEMISTRY BRANCH CHEMISTRY DIVISION HOWARD W. KRUSE respectively. The former compound was identical U. S. NAVAL ORDNANCETESTSTATION to A7-cholesten-3p-ol, and the latter sterol (less CHINA LAKE,CALIFORNIA WILLIAMR. MCBRIDR polar) was identical to I (Anal. Calcd. for CW RECEIVED ~'OVEMBER 2, 1957 C, 84.00; H, 12.00. Found: C, 83.22; H, 12.01) by m.m.p. and infrared spectrum, Evidence has been obtained which tentatively rules out 4,4ISOLATION AND SYNTHESIS OF A NEW STEROL dimethyl-A7-cholesten-3p-01.Future publication of FROM RAT FECES112 the data will be made. The possibility of the 2(a Sir: or p)-methyl isomers cannot as yet be eliminated, I n previous reports, 3.4 the presence of a new sterol but is unlikely on biological grounds. Others13*14 (I) in rat feces was announced. Separation from have reported the monoalkylation of A4-3-onesterthe less polar coprostanyl p-phenyl azobenzoate oids a t position 4 using conditions similar to ours. was effected by chromatography of the mixed es- Since these conditions favor the more stable equaters on silicic acid:Celite (2:1)5 columns using pe- torial configuration, it appears likely that I is 4atroleum ether (b.p., 90-95'). Saponification of (I) methyl-A7-cholesten-3p-01. The origin of I sugp-phenyl azobenzoate, and crystallization of the en- gests the possibility that this sterol arises from the suing sterol (I) from absolute ethanol yielded thin D. R. Idler, S. W. Nicksic, D. R. Johnson, V. W. Meloche, needles; m.p. 146-147', [ a I z 5 D 0.00 in chloroform H .(6) A. Schuette and C. A. Baumann, THIS JOWRNAL, 7 6 , 1712 (1953) (1) This work was supported by a research grant (H-2458 C, CS) from the National Institutes of Health, U. S. Public Health Services. (2) Some of the properties of this sterol were studied in collaboration with D. L. Coleman and C. A. Baumann, Department of Biochemistry, University of Wisconsin. (3) W. W. Wells, D. L. Coleman and C. A. Baumann, Arch. Biochcm. Biophys., S7, 437 (1955). ( 4 ) D. L. Coleman, W. W. Wells and C. A. Baumann, ibid., 60, 412 (1956). (5) D. R. Idler and C. A. Baumann, J . Bid. Chcm., 195,623 (1952).
(7) D. R . Idler and C. A . Baumann. J . B i d . Chcm., 203, 380 (1953). (8) H.Wieland and W. Benend, A n n . Chcm., SS4, 1 (1943). (9) A. Windaus and G. Zhhlsdorff, A n n . , S36, 204 (1938). (IO) E. Weisenberger, Mikrochcm. Microchim. Acla, 3 3 , 51 (1947). (11) R. B. Woodward, A. A. Patchett, D. H. R . Barton, D.A. Ives and R . B. Kelly, J . Chcm. Soc., 1131 (1957). (12) W. Bergmann, J . B i d . Chcm., 132, 471 (1940). (13) F.Sondheimer and Y.Mazur, THIS JOURNAL, 79, 2806 (1957). (14) N. W. Atwater, ibid., 79, 5315 (1957).
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TO THE EDITOR COMMUNICATIONS
intestinal mucosa,3 and that it may be an intermediate in the biosynthesis of cholesterol. Evidence for the existence of demethylated intermediates in the conversion of lanosterol to cholesterol have been reported. l5 Acknowledgment.-We are indebted to Dr Hans No11 for infrared measurements, and to Drs. Klaus Hofmann and Arvid Ek for helpful suggestions.
(11). Finally, rescinnatnine and pseudoreserpinr have been correlated with reserpine216' (111, Y = OMe). However, no data chemically relnting the. three groups of compounds have been reported yet. Palladium-maleic acid dehydrogenationg of reserpine (111, Y = OMe) yielded its tetradehydro derivative (47%) as perchlorate, m.p. 194-1!)Ti0 (Found for C33H37013NzC1CH30H : C, Ei5.11; H , 6.02; N, 3.50). Hydrogenation of the latter with platinum in acetic acidg gave the demethoxytctra(15) F. Gautschi and K.Bloch TsI3 TOIIRNAI.. 79, 684 (19 57) hydrotetradehydro compound IV ( G l % ) , m.p. 1%BIOCHEMISTRY DEPARTMEKT UNIVERSITYOF PITTSBURGH WILLIAMW. WELLS 1S9', Xmpx 250 mp (log E 4.16)) 270 mp (log E 4.101 SCHOOL OF MEDICINE DEWEYH. NEIDERHISER and 335 mp (log E 3.61), [CY]D -40' (chloroform) PITTSBURGH, PENNSYLVANIA (Found for C32H3501~N2C1: C, 55.94; H, 5.25; RECEIVEDNOVEMBER 15, 1957 N, 4.25). The identical product, checked by m.p., mixed m.p., infrared and ultraviolet specTHE STEREOCHEMICAL INTERRELATIONSHIP OF tra, and specific rotation, was obtained by the cataTHE YOHIMBINE-TYPE ALKALOIDS' lytic hydrogenation of the tetradehydro derivative Sir : of deserpidine (111, Y = H).*b These results conWe wish to report the completion of the first stitute the first chemical correlation of compounds phase of our continuing studies of the stereointer- of group I1 and 111, and represent a potentially relationship of indole alkaloids containing the ring useful method of interrelating the many ring A system of yohimbine, ajmalicine and corynantheine, oxygenated ajmalicine-type alkaloids with alstoniiie ie., the steric relationship of all yohimbine-type and serpentine.2 alkaloids. Corynanthine, @-yohimbine and pseudoyohimbine have all been related to yohimbinej2whose absolute configuration (I) was ascertained by molecular rotation difference3and optical rotatory dispersion' studies. Similarly, alloyohimbine, rauwolscine, deserpidine, raunescine and isoraunescine have been interrelated with 3-epi-c~-yohimbine~,~,~
u\ I /
When apoyohimbic acid hydrochloride, readily derivable from yohimbine2 (I), was exposed to a Schmidt reaction, 16-yohimbone (V), m.p. 256' (dec.), [a]D -86.1' (pyridine) (Found for C19H22ONz: C, 77.7; H, 7.28; N, 9.3) was obtained in 17% yield.l0 The same reaction, carried out on the apo derivative of 3-e~i-a-yohimbine5~ (11),led to R ketone (17%) whose m.p. 254-256', [ a ] D +85.0° (pyridine), and infrared spectrum, identical with that of V, proved it to be the enantiomer of 16-yo-
\/0\
(1) This work was supported in part by a research grant from Ciba Pharmaceutical Products, Inc., and from the National Institutes of Health, Public Health Service, Department of Health, Education and Welfare (M1301). (2) For a review of t h e stereochemistry of indole alkaloids cf, J . E. Saxton, Quart. Revs., 10, 108 (1956). (3) W. Klyne, Cheinislry and Indurlry, 1032 (1953). (4) C. Djerassi, R . Riniker and B. Riniker, THISJ O U R N A L , 78, 6862 (1956). (5) (a) C. F. Huebner and E. Schlittler, ibid., 79, 250 (1957); (h) E. E. van Tamelen and C. W. Taylor, ibid., 79, 5256 (1957). (6) For a discussion of the absolute configuration of these alkaloids based on molecular rotation difference data cf. E. Schlittler, T h e Chemistry of Rauwolfia Alkaloids. in "Rauwolfia," I.ittle, Brown and C o m p a n y , Boston, 19\57.
l i
04%'
V (7) M. W. Klohs, F. Keiler, R . E. Williams a n d G W. Kussrrow, THISJOURNAL, 79, 3763 (1957). (8) (a) E. Wenkert and L. H. Liu, E r p e i i e n f i a , 11, 362 (1SB.jii; (b) E. Wenkert and D. K . Roychaudhuri, in press. (9) Cf.H. Schwarz and E. Schlittler, IIPIo. Chint. A r l i r 3 4 , 629 (1951).
(lo) Since the completion of this work t h e synthesis of I(i-ketu. yohimbane has been reported also by R K. H i l l : ~ n dK . X I u e n c i i , J. Org. Cizem., 22, 1276 (1957).
