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COMMUNICATIONS T O T H E EDITOR THE STERIC STRUCTURE OF BSTRIOL ARD RELATED STEROIDS
described, cis-oid isoestrio1-Al0 (acetonide, m. p. 183.5-184.5', uncor.) and trans-oidg estriol are Sir: obtained. Isoestriol-A and estriol are therefore, Stodola, et ad.,'#* have shown that the zinc- respectively, A1.**C-estratriene-3, 16(a),17(a)-triol acetic acid reduction of 16-oximino-17-keto- and A1#a*6-estratriene-3, 16( 17(a)-triol. steroids followed by acetylation results in the Ruzicka and co-workersl1*l2have recently preformation of 16-keto-17-acetoxysteroids.The pared in the estrogen and androstane series 16,17structure of the intermediate a-keto1 was not de- glycols which they designated as A1-aJ-estrat.rienetermined. 3,16(a),17(a)-trioll and androstane-3 (P), 16(a), We have found that 16-keto-17-acetoxysteroids 17(a)-tri01,~~ respectively. These two triols must made by the Stodola method possess the 17-group be cis-oid a t Cl6-Cl7, since they were formed in the a-position, since As-androstene-3(j3),17- through the osmium tetroxide addition to the diol-16-0ne &acetate* so prepared readil forms a proper A%teroid. However, as neither of the 16-diethyl thioacetala (m. p. 136.5-138 , uncor.) two triols is identical with isoestriol-A or with the which, upon hydrogenolysis,' yields the known saturated androstene-triol (m. p. 251-2S0, unAK-androstene-3(@),17(a)-diol diacetate'J identi- cor.) of Butenandt, we suggest that the two comfied by comparison with an authentic sample. pounds are in reality A1J6-estratriene-3,IS(@, Furthermore, we feel certain that no rearrange- 17(8)-triol and androstane-3 (g), IS(@,17(8)-triol. ment occurs in the acetylation of a-ketols pre(10) M. H. Huffman and H. H. Darby, TEISJOURNAL, 66, 150 pared by the Stodola method, and that these (1944). ketols are also 16-keto-l7(a)-hydroxysteroids, (11) V. Relog, L. R u d c h and P. Widand, H c b . Chim. A d o , S8, (1945). because: (1) the acetylated a-keto1 may be 255(12) L. Ruricka, V. Prelog and P. Wielnnd, W . .SO, 1608 (1945). saponified to regenerate the original a-keto1 from DEPARTKBNT OF BIOCHEMISTRY which it was prepared; (2) the same acetylated SOUTHWESTERN MEDICALCOLLEGE M u N. HUFFMAS a-keto1 results on esterification by long standing DALLAS,TEXAS MARY H A RLon ~ in pyridineacetic anhydride or by almost inRECBIVEDJars 11,1947 stantaneous acetylation according to Ciusa and S o l l a ~ z o the , ~ yields being virtually identical in both instances. Hydrogenation of Ab-androstene-3(8),17(a)diol-16-one diacetate with Raney nickel in ethanol Sir: (Stodola, et aL1)or in ethyl acetate-ethanol (our In a previous communication,1 it was pointed confirmation) yields Butenandt's tri0l.l Since out that the form of the A-dc curve of nthis triol is known to be cis-oid at C ~ O - C its I ~ , ~octadecylpyridonium chloride in water is similar structure must be AE-androstene3(8),16(a),17- to that of the paraflinchah electrolytes in general (a)-triol. If A6-androstene-3(B),17(a)diol-ls- (i. e., A decreases abruptly a t the critical concenone (Stodola prepared, m. p. 200-202', uncor.) tration), but that in water-methanol mixtures is reduced with sodium amalgam in excess dilute containing 10 to 35% of methanol (by wt.), A ethanolic acetic acid (40'), both Butenandt's passes through a maximum a t concentrations in triol (cis-oid) and Hirschmann's triol8 (trans- the neighborhood of the critical concentration in oid) may be obtained. Hirschmann's triol (trans- water. Maxima in the A-dc curves in suitoid at c16-c179) is therefore A5-androstene-3(@), able water-methanol mixtures, but not in water, 16( 17(a)-triol. have also been found for the following n-octaIf, in the estrogen series, A1*a~6-estratriene-3,17decyltrimethylammonium salts: chloride, bro(a)-diol-I&one (Stodola prepared, m. p. 234- mate and formate. On the other hand, the corre237', uncor.) is reduced with sodium amalgam as sponding nitrate, bromide and oxalate exhibit ( 1 ) F. H . Stodola, E. C. Kenddl and B. F. McKenrie. J . Orx. the usual "break point" phenomenon in mixtures Chrm., 8 , 841 (1941). containing 0 to 38% of methanol. (2) F. H. Stodola and E. C. Kenddl, ibid.. T, 338 (1942). We now find that the existence of a maximum in (3) S. Bernstein and L. Dorfmnn, T u n JOURNAL, a,1152 (1946). (4) L. Ruricka and A. Wettstdn, Hrlo. Chim. Acfo, 18, 1264 A is not limited to water-methanol mixtures as is (1935). clearly shown in Fig. 1, where A has been plotted (5) A. Butroandt and G. Hanisch. 2. physroi. Chrm.. SST, 89 as a function of 4 for n-hexadesylpyridonium io(1936). date (curve 1) and n-octadecylpyridonium iodate (8) R . Ciusa nod 0. .%llasro. AIR. cham. opplicolo. SS, 72 (1943). (curve 2) in water at 25'. In the first mentioned (7) A. Buteoandt. J . Schmidt-ThomC and T . Weisr. Bn.. TS, 417 case, the peak is approximately 1 A unit high, and (1939). in the second, approximately 10 A Units. ( 8 ) H.Hinrhnuoo. J . Biol. C h . ,160,863 (1948).
a),
B
a),
(9) M . N. Huffmon and M . H. Lott. ibid.. lU,786 (1946).
(1) B v m . Criegrr and h u m , Tmm J o m n l ~m, . 1187 (1040).
COMWNICATIONS TO THE EDITOR
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Vol. 69
lated on the weight of glycol, not on the glycolcopper complex. The magnitude of the optical rotations (1200') in claprammmium is striking. The sign and nitude of the rotations indicate that the form may be oriented as are the 2- and 3-hydroxyl groups of substituted methyl glycoside and the D - ( - ) - form as are the 3- and %-hydroxylgroups of substituted methyl glucoside. And such a condition is distinctly possible in view of the configurations which have been assigned to these two butanediols by M o d and Auernheimer.' Specific rotations for the appropriately substituted methyl glucosides in cuprammonium have been reported.* They were +M0 (436 mp) for methyl 2-methyl-/3-glucoside, and - 1008' (436 m p ) for methyl 4-methyl-B-glucoside.
~-21
TABLEI SPECrprC ROTATION OF 2,3-BUTANEDZOL S o l ~ a and t light mwcc L-(+)-forrn o-(-)-form
I
I
I
0.02
0.04
0.M
Water, Dline Water, Hg blue line (436 mp) Cuprammonium, Hg blue line
+ +
11.8' 20.6"
- 1200'
-
11.1" 19.2" +1200"
-
The samples of optically pure butanediols used in the investigation were supplied by Dr. Robert Fig. l.-Cor~ductancecurves in water at 25': (1) nhuadecylpyridonium iodate; (2) n-ochdecylpyridonium D. Coghill, formerly head of the fermentation division of the Northern Regional Research Laboiodate. ratory. W e the addition of methanol in suitable ( 1 ) S. A. Maell and A. H. Auanhdrncr, Tars Joaanu,, 64,79!4amounts to water solutions of certain paraffin- 796 (1944). (2) R. E. Reeves, 1. Bid. C h . .lW,49-S6 (1944). chain salts gives rise to a maximum in A, the SOUTI~ERN REGION&RESEARCH LABORATORY addition is not indispensable in,some instances, BURBAUOF AGRICULTURA~ AND INDUSTRIAL CHEXIS~RY nor is it sufficient to produce a maximum in others. A cnrcv~~iw RESEARCH . ADMINISTRATZON It is evident that the phenomenon is closely re- u. s. DEPARTMENT OF AGRICULTURE lated to the nature of the "gegenion." NEWORLEANS 19, LA. RICHARD E. REEVES Sufficient results have now been obtained to perRECEIVED APRXL 14,1947 mit of formulating a fairly general description of the electrical conductance of solutions of paraffinchain electrolptes in watq+xganic solvent mix- An ALBlJbUN FEUCTIOH ISOLATBD FROM HUMAH PLASbU AS A CRYSTALLIHE MERCURIC SALT tures; the details of .this work will be presented in Sir: the near future. Following the addition of mercuric chloride to GEORGE L. BROWN DEPARTYBNT OF CHEMISIRY PHILIPF.GRIBCEI~ a solution of human serum albumin, a fraction of BROWNU"8RSITY E. CKARLBS E v ~ n s the albumin crystallized. The best yield was ob~ O V I D B N CR. B ,I. CKARLES A. KRAUS tained when approximately one-third mole merRECEIVEDJUNE 12,1947 curic chloride per mole albumin was added to a 15% solution of Fraction V' or to human serum albumin crystallized with decanol,) in 15% C ~ M O ~ M - 2 , 3 - B U T A N E D I OCOM.€'LBxBs L ethanol at -5O, a t PH 5.2, I'/2 = 0.02. More sir: than half the senun albumin separated after In connection with a study of the properties of prolonged standing, or within a few days following cuprammoniurn-glucoside complexes the behavior seeding, in the form of rhombic or hexagonal of the optically active 2,3-tmtanediols in cupram- plates. Sparingly soluble in water, the crystals dissolved readily in 0.02 M sodium chloride and monium hydroxide solutibn has been observed. In Table I are given the specific rotations for could be recrystallized by the addition of ethanol. the D-(-)-and L-(+)-forms of the two butane(1) E. J. C o b , L. E. Strong, W. L. Hughes, Jr.. D. J. Mulford, diols in water (approx. 1% gl col concn.) and in J. N. Ashworth, M.Melin and H. L. Taylor, THIS JOUXNAL, U,469 cuprammonium. (approx. 0 . 8 6 ) . The rotations (ISM). (2) T h a r O ~ O ~ T ~ O which M , rill pruenUy he reported in full, were measured at 25'. The cuprammonium followed upon. and nre clacly relsted to, the methods for the cry.contained 15 g. of copper and 240 g. of ammonia tslliutlon of mrn dbamiru dencribel d r w h e r e in this iuue. Cohn, per liter. The rotations on this solvent are calcu- Hughannd W a r e ,(bid., eB, 1753 (1947).
