COMMUNICATIONS TO THE EDITOR
Oct. 20, 1953
5135
of the valine methyl carbons. Indirect proof that carbon 3 of pyruvate can provide the carbon for the valine methyl carbons was obtained in the last experiment in the table in which it was found that carbon 1 of glucose, presumably v i a 3-labeled pyruvate, appeared preponderantly in the methyl carbons of valine. I n speculating on the mechanism of this conversion, the equal incorporation of lactate carbon 2 DEPARTMENT OF PHYSICS T. G. NORTHROPinto valine carbons 2 and 3 suggests a direct IOWA STATE COLLEGE R. L. NUTTER coupling of 2 lactate a-carbons. The only conR.L. SINSHEIMERceivable biological reaction of similar type is the AMES,IOWA RECEIVED JULY 24, 1953 condensation of pyruvate and acetaldehyde to yield acetolactic acid.4 From the structure of this substance it is not unreasonable to assume that VALINE BIOSYNTHESIS IN migration of a methyl group might occur, as in TORULOPSIS UTILIS1 the pinacol or related rearrangements, to yield sir: Results are reported herein which indicate that P,p'-dimethylpyruvic acid, a logical precursor of the carbon chain of lactic acid is a direct precursor valine. Some precedent for the biological occurof the valine carbon skeleton. The materials for rence of methyl group migration has recently been this investigation were specimens of labeled valine provided by Woodward and B10ch.~ This pathisolated, by slight modifications of the method of way is under further investigation. Moore and Stein,2 from hydrolysates of yeast 8 grown in the presence of C14-labeled tracer substances. Growth of the cells and other experimental details have been described previously. Submission of the valines to a degradation procedure for radioactivity assay of each of the four .different valine carbons gave the results shown in the table. Glycine, acetate, and lactate carboxyl ," I DISTRIBUTION OF LABELED CARBONS IN VALINE CARBON scattering determinations of molecular weights, the molecular weights of DNA as determined by Smith and Sheffer, Katz, and Doty and Bunce would seem to be too high by 37%. It should be pointed out that Tennent and Vilbrandt did not specify the wave length light used in their refractive measurements; hence direct comparison of their value of 0.180 with the above value of 0.201 should not be made.
Values are specific activities in cpm of BaCOa, corrected for equal initial activities of substrates. 7
Valine carbon number" 1 2 3 4,4'
Precursors
Acetate Glycine Lactate CHa- -COOH - C H r -COOH -CHOH- -COOH 10.5 170 30 575 45 905 1.55 -3 3fi5 -4 750 150 0 310 0 700 155 0 335 0 20
$*
Numbering begins with valine carboxyl carbon. tone not further degraded.
Glucose1-C"
-CHO 25 45 50 358
Ace-
SdHa-sC-OH
d!OOH
+
1
1COOH
LANKENAU HOSPITAL RESEARCH INSTITUTE MURRAY STRASSMAN~ AND INSTITUTE FOR CANCER RESEARCH ALICEJ. THOMAS PHILADELPHIA 11, PA. SIDNEY WEINHOUSE RECEIVED AUGUST14, 1953 (4) T . P. Singer and J. Pensky, Biochim. et B i o g h y s . Acta, 9, 316 (1952). (5) R. B. Woodward and K. Bloch, THISJOURNAL, '76, 2023 (1953). (6) Postdoctoral Fellow of the National Institutes of Health, Department of Health, Education and Welfare.
carbons appeared only in the valine carboxyl; glycine and acetate a-carbons appeared approximately equally in all of the valine non-carboxyl carbons; and the lactate a-carbon appeared equally REARRANGEMENT OF THE STEROID C/D RINGS. and nearly exclusively in carbons 2 and 3 of valine. SYNTHESIS OF AN 1 1-KET0-Al3(l7~)-C-NOR/DThe relatively low incorporation of acetate and HOMO-STEROID glycine carbons precluded these substances, as well Sir: as citric acid cycle components, as direct precursors Hecogenin (I) in the form of its toluene p of valine. However, the relatively high incor- sulfonylhydrazone derivative (Ia), m.p. 259-60' poration of lactate carbons suggested that lactate (dec.); found: S, 5.39; XgzoH226 mp (4.1), was or pyruvate may be the direct source of carbons for submitted to a BarnfordStevens rearrangement' valine biosynthesis, and that acetate and glycine with sodium in ethylene glycol to yield the Ccarbons were incorporated in valine via their prior nor/D-homo-sapogenin (11) m.p. ca. 110" ; found: conversion to pyruvate. The observed distribu- C, 77.95; H, 10.00. Acetate (IIa) m.p. 142-144'; tion of activity is in accord with the conversion of [ ( Y ] ~ ~ D -52.6 (CHC13). Found: C, 76.03; H, glycine to pyruvate via 'serine, and of acetate to 9.72. I1 was found to be identical with a compyruvate via the citric acid cycle and oxalacetate. panion olefin isolated together with I11 from the If this postulation is correct, it follows that the solvolytic rearrangement of the rockogenin derivmethyl carbon of pyruvate should be the precursor ative (IV)2; I1 was also formed in good yield (1) Aided by grants from the Atomic Energy Commission, contract from I11 on treatment of the latter with formic acid No. AT(30-1)777; the American Cancer Society; and the National a t room temperature. The endocyclic olefin (11) Cancer Institute of the Department of Health, Education and Welfare. (2) S. Moore and W. H. Stein, J . B i d . Chem.. 191, 663 (1951). (3) M. Strassman and S. Weinhouse, THISJOURNAL, '74, 1726 (1952).
(1) W. R. Bamford and T . S. Stevens, J . Chcm. SOC.,4785 (1962). (2) R. Hirschmann, C. S. Snoddy, Jr., and N. L. Wendler, THIS JOURNAL, '74, 2693 (1952).
BOOKREVIEWS
5136
VOl. 75 H
osmium tetroxide to a triol which on treatiiient with acetic anhydride in pyridine at room temI, R,0 = 11, K, €I perature gave only a monoacetate derivative m.p. Ia, R, C ~ H I S O ~ N H=S IIa, R, CHaCO 215-15"; [ a r l Z 6 ~ -39.3" (CHC13). Found: C, 71.00; H, 9.45. .- J I n a similar manner 11-ketohecogenin(V) was converted to its toluene 9-sulfonylhyI CHL C~aS02c1\1 l\o/ drazone derivative (Va), m.p. 156-158" I/ I 0 (dec.); XALFlo" 228 mp (3.90), 275 mp (3.82). Found: N, 434. The latter rearranged on treatment with potassium hydroxide in refluxing ethylene glycol to give A P y -I the 1l-keto-A18(17a)-C-nor/D-hmo-sapogenin (VI) 190-192"; [ct]24D -78.4' (CHClJ; c0o/'VV AcO /vv AXCH" ultraviolet 255 mp (4.17), 350 mp max I (2.88); X X ~ ~ Cinfrared " 5.85 p, 6.1 p (more (CHs)XOnCH3 I11 IV intense). Found: C, 75.54; H, 9.62. Acetate: (VIa) m.p. 178.5-179.5'; [ a ] " -80.7" ~ A/ (CWCla); AXE?;o" 225 mp (4.18), 350 mp (2.87). ' I Found: C, 73.74; H, 8.92. _ _ R I ' 0 The spectral characteristics of VI are essentially 17u I the same as those of jervine (VII).4 Of partic0 \ li,j\/'\ ular note is the unique reversal in intensity of the I --+ I C=O and C=C bands in the infrared spectra of AA, - -I fiA/V both VI and jervine. K0
~
mg.
1 7
>-
\(-J
I
I
H d b%'
v, R, 0
RdVv
=
Va, R , C ~ H ~ S O L S H =S
VI, R, €1 VIa, R, CHaCO
exhibited no absorption in the double bond region of the infrared and was smoothly converted with
(3) C DjerdSSl, H. Ringold and G Rosenkranz, ~ 6 2 d 73, 1613 (1961) (4) J. Fried, 0 Wrntersteiner, hI Moore B hl Iselin and A Klingsberg, ibrd , 75, 2970 (1951)
RESEARCH LABORATORIES CLAUDEF HISKEV MERCK& Co , I,.ic RALPHHIRSCHMANN RAHWAY, N. J. N L WENDLER RECEIVED ShPlEMBER 14, 1953
BOOK REVIEWS Computing Methods and the Phase Problem in X-Ray Crptal Analysis. Report of a Conference Held at T h e Pennsylvania State College, April 6-8, 1960. By RAY PEPIN(Editor). The X-Ray Crystal Analysis Laboratory, Department of Physics, The Pennsylvania State College, State College, Pa. 1952. xvii 390 pp. 21.6 X 27.6 cm. Price, $7.50. The conference report presented in this volume is the result of a meeting of about fifty specialists in the field of crystal structure determination from X-ray ditfraction data, which wa8 or nized by Professor Ray Pepinsky at the Pennsylvania &ite College under the joint sponsorship of the Rockefeller Foundation and the Ofice of Naval Research. It was the intent of the conference and the resulting report to review the current status of the problem posed
+
by the lack of experimental information on the phases of the X-ray beams scattered by a given crystal and also of the progress in computing methods applicable to crystal structure determination. This intent has been very successfully ful!illed, and this collected review is a basic contribution to the literature of that field. The report consists essentially of four parts. The first is a group of ten papers dealing with the basic mathematical problems involved in t h e application of Fourier t r a n s f m a tions in the analysis of the experimental intensity data. Following an introduction by R. Pepinsky and a general statement of the problem by J. M. Bijvoet, papers by 6.A. Beevm and A. L. Patterson discuss the structural information which can be obtained from the "Patterson" synthesis using IFl2 coefficients. M. J. Buerger then presents an-
