April 5 , 1958
COMMUNICATIONS TO THE EDITOR
1769
copolymer" character presumably is responsible for the variation in X-ray and physical property data observed with type I11 poly- (methyl methacrylate). The exact nature of the crystals themselves is under more intensive investigation.
the lower range expected for a stable carbinolamine ether.' (2) The infrared spectrum showed no absorption in the hydroxyl region. (3) The 16-acetate group survived prolonged treatment with methanol and triethylamine, an indication of the T. G. Fox absence of an axial hydroxyl a t C20 t o facilitate B. S. GARRETT methanolysis.4 (4) Chromic anhydride-pyridine RESEARCH LABORATORIES W. E. GOODE oxidation of IIIa afforded a neutral product (m.p. ROHMAND HAASCOMPANY SERGE GRATCH 263-264' dec., [a]D f54" diox., 6.07 p , J. F. KINCAID PHILADELPHIA, PA. ALDENLEESPELL -NCO-, found, C, 60.59; H, 7.17)) evidently the J. D. STROUPE formamido ketone IVa. Acid hydrolysis afforded one mole equivalent of formic acid. Alkaline hyRECEIVED FEBRUARY 8, 1958 drolysis of the corresponding formamido ketone 6.07 IVb (m.p. 288" dec., [a]D +52" py., &A:: THE CONFIGURATION OF CEVINE p ; found, C,60.98;H, 7.08) derived from cevine Sir: gave the desacetyl-formamido-ketone IVc (m.p. The configurations of nine (C3, Cq, Cg, CS,(210, 259-260' dec., [CY]D 4-22' py., found, c, 61.66; CIZ,C14, C1,,C26) of the fourteen asymmetric cen- H, 7.24). In addition to the amide band, the inters of cevine were established almost simultane- frared spectrum of this substance exhibited normal ously with the climactic structure elucidation in ketone absorption a t 5.85 p , 1954-55.1-3 Recent work in our laboratory made The alternative formulations V and VI for the possible assignment of configuration at CM and CZO oxide and formamido ketone were excluded on the and provides support for previously considered' basis of the following evidence. (1) The fonnconfigurational a$signments a t CS and C I ~ .Evi~ amido ketone IVb derived from cevine readily dence is presented herewith for assignment of con- formed a semicarbazone (m.p. 273-274" dec.; figuration a t the remaining asymmetric center found, C, 57.91; H, 6.80, N, 6.93). ( 2 ) The ((222) of cevine which now can be represented comformamido ketone IVa showed active methylene pletely by formula I. It is highly probable that group reactivity in the Zimmermann tests and upon closely related alkaloids, such as zygadenine and treatment in alkaline solution with furfural. (3) germine, also have this basic configuration. The corresponding formamido ketone (m.p. 253Oxidation of veracevine D-orthoacetate triace- 255" dec., [ a ] -83" ~ diox.; found, D, 60.96; H, tate (IIa)5 (pKa' 7.4) with ;N-bromosuccinimide6 7.10) from cevagenine-C-orthoacetate diacetate5 yielded a dehydro compound (m.p. 280-282' dec., was, like the parent alkaloid, stable to lead tetra[ a ] +33" ~ diox.; found, C, 63.51; H, 7.35; Ac, acetate. This behavior is characteristic of a rigid trans diaxial glycol system a t C17,C20, a situation clearly not satisfied by VI. The bridged /3-oriented oxide structure of I I I a and b requires that the hydrogen a t C52 be aoriented. T h a t the stereochemical integrity of the molecule was preserved during the oxide formation was demonstrated by catalytic hydrogenation of I I I a over platinum in acetic acid. Two moleequivalents of hydrogen was absorbed to give a substance identical with the product of hydrogenation (one mole-equivalent uptake) of IIa, namely veracevine-D-dihydroorthoacetate triacetate (m.p. 299300' dec., [ a ] -4-21' ~ diox.; found, C, 63.53; H, 7.85; Ac, 19.98).'s9 (7) H. Bloom and L. H Briggs, J. Chem. Soc ,3591 (1952) ( 8 ) W. Zimmermaaa, Z . physiol. Chem., 233, 257 (1935); D.H. R.
+b ,__ --0
Re
I1 I11 a (R1 = B-OAc,R2 = 0.4~; R 3 = At) b (R1 = or-OAc, R * = OAc; R3 = Ac) c (R' = a-OH, R2 = OH; R 3 = H)
IV
25.52), evidently the bridged oxide I I I a for the following reasons. (1) The QKa' (found, 3.8) was in (1) D.H. R. Barton, C. J. W. Brooks and P. De Mayo, J. Chem. SOC., 3950 (1954). (2) F. Gautschi, 0. Jeger, V. Prelog and R. B. Woodward, Helo. Chim. A d a , 38, 296 (1955). (3) S. M . Kupchan, THISJOURNAL, 77,686 (1955). (4) S.M.Kupchan and W. S. Johnson, ibid., 78,3864 (1956). ( 5 ) S. M .Kupchan, D. Lavie, C. V. Deliwala and B. Y.A. Andoh, ibid.. 1 6 , 5519 (1953). (6) C f . 0. E.Edwards, F. H. Clarke and B. Douglas, Can. J . Ckcm., 32, 235 (1954).
Barton and P. de Mayo, J. Chem. SOC.,887 (1954). (9) This work was supported in part by a grant (H-2275 ('22)) from the National Heart Institute of the National Institute,a of Health.
DEPARTMENTS OF CHEMISTRY S. MORRISKUPCHAN PHARMACEUTICAL CHEMISTRY S. JOHNSON WILLIAM UNIVERSITY OF WISCONSIN MADISON, WISCONSIN S. RAJAGOPALAN RECEIVED JANUARY 27. 1958
AND
1601-CHLORO- AND 16a-IODOESTRONE METHYL ETHER, NEW AND POTENT LIPID-SHIFTING AGENTS
Sir: The problem of finding estrogen-like substances capable of altering blood lipid composition, and which a t the same time are not feminizing, is important in clinical treatment of atherosclerosis. A
