COMMUNICATIONS TO THE EDITOR
474
ACTIDIONE, AN ANTIBIOTIC FROM STREPTOMYCES GRISEUS
Sir: It has been found in this Laboratory t h a t streptomycin-producing strains of Streptomyces griseus
Vol. 69
Toxicity tests, intravenously in mice, indicate an LD50 of approximately 150 mg. per kg. Actidione has been assayed satisfactorily in concentrations as low as 0.001 mg. per ml. by an adaptation of the paper-disk plate method for strepto -
TABLE I c
C
,---CL26D-
Actidione Diacetate Dioxime
Disemicarbazone a I n methanol
ca
Sf. p., ' C .
Deg.
115-116.5 143-145 203 -204 176-178
-2.8 f24.6
3.7
.... ....
... .,,
6.6
Formula
C1,HI.2SP07 C31H16NZ00 C27HaiN407 C29H,8X807
Calcd.
Found
64.01 63.03 60.42 56.12
03.74 02.98 60.66 55.53
Percentage composition H N Calcd. Found Calcd. Found
8.36
8.35
7.85 7.89 8 . 2 7 8.29 7.79
7.70
5.53 5.44 4.74 4.70 10.44 9.85 18.05 17.71
produce a second antibiotic which has little or no mycin3 using Saccharomyces pastorianus ATCC activity against bacteria but is very effective 2366 as the test organism. against many yeasts. The crude product was (3) Loo, Skell, Thornberry, Ehrlich, McGuire, Savage and isolated from streptomycin beers by adsorbing on Sylvester, ibid., 60, 701 (1945). carbon, eluting with 80% acetone, distilling the RESEARCH BYROKE. LEACH LABORATORIES JARED H. FORD acetone and extracting the remaining aqueous THEUPJOHNCOMPASY ALMAJ. ~VHIFFEN MICHIGAN solution with chloroform. The chloroform ex- KALAMAZOO, RECEIVED JASUARY 17, 1947 tract was decolorized with carbon and evaporated. -After purification of this crude product by counter-current distribution between benzene THE POSSIBILITY OF FREE ROTATION IN THE SILICONES and water,l it was obtained in crystalline form. Several recrystallizations from amyl acetate S i r : yielded colorless plates, m.p. 113-1 1A.5", [ L Y ] ? ~ D The low boiling points and small temperature - 2 3 " (c 9 6, methanol). Analytical data are in coefficients of viscosity of the silicones have led good agreement with the formula C27H42N207 to the view t h a t siloxane bonds result in low CO(mol. wt. 50'7). The molecular weight (cryo- hesive forces.la,b We have been determining the scopic in benzene) varied from 420 to S T 3 , de- crystal structure of octamethylspiro [5.5]pentapending upon the concentration. siloxane2 to see whether structural considerations Treatment of the compound with acetic anhy- would shed some light on this anomalous behavior. dride and sodium acetate a t room temperature Oxygen would be expected t o form covalent p produced a biologically inactive diacetate, m.p. bonds a t 90'. The Si-0-Si bond angle should be 14:3-143', I L Y ] ? ~ D +24.(io (c 3.7, methanol). The increased somewhat b y repulsion resulting from dioxirne melted a t 203-201' and the disemicar- the ionic character of the S i 0 bond. However, bazone a t 176-178'. We suggest that this com- Sauer and Mead3 calculate from the dipole mopound be named acfidione since it appears to be a ment of hexamethyldisiloxane an angle of 160 =e diketone and is produced by an actinomycete. 15' and Frevel and Hunter4 report a planar ring Xctidione is rapidly inactivated by dilute alkali for the cyclic trimer [(CH3)2Si0]3. a t room temperature with the formation of a fraThe spirosiloxane compound crystallizes with grant, dextrorotatory, volatile ketone; semicarba- the space group Dit(I%rnd). There are fou; zone, m.p. 190-193'. Refluxing with dilute sulfuric wid does not produce the volatile ketone, but molecules in the unit cell, each molecule consistwhen the hydrolysate is made strongly alkaline a ing of two planar six-membered rings linked a t low niolecular weight amine is evolved. Further 90' through a c o m m p Si atom. The S i 0 distance is about 1.64 A., comparable to distances degradation studies are now in progress. An antibiotic spectrum of crystalline actidione found in the inorganic si!icates and considerably was found to be very similar to t h a t previously less than the value 1.83 A. obtained from the coreported for crude preparations.? When tested valent radiusosum for Si and 0. The Si-C disagainst twclve representative bacteria it failed to tance is 1 .90 A., the expected covalent sum. Despite reasonable agreement between calcuinhibit :it concentrations up to 1 mg. per ml. lated and observed F' values for reflections with Crystalline actidione inhibits the fungal pathogen, lrkl indices, i t proved impossible t o refine low Cryptococczis iieofonimn Y, in concentrations as low parameters by conventional Fourier methods. as 0.0002 nig. per ml. This high order of activity Electron density projections and sections indisuggests its, possible usefulness in the treatment (1) ca) Hunter, Warrick, Hyde and Currie, THISJOTIRKAL, 68, of crjptococcosis, a rare but usually fatal disease. 2284 (1946); fb) D. F. Wilcock, ibid., 68, 6R1 (1946). (1) Craig, Golumbic, Uighton and Titus, J . R i d . Chem., 161, 321 (ISG). ( 2 ) Whiffen, Bohonos and Emerson, J. Bacl., 63, 610 (1946).
( 2 ) D. W. Scott, i b i d . , 68, 356 (1946). ( 3 ) Sauer and Mead, i b i d . , 68, 1794 (1046). (4) Frevel and Hunter, i b i d . , 67, 2276 (1945).
