2026
Vol. 80
COMMUNICATIONS TO THE EDITOR
ETHYNYLATED DERIVATIVES RELATED TO ADRENOSTERONE AND A STEROIDAL EFFECT ON EXPERIMENTAL HYPERLIPAEMIA
( I ) : m.p. 303", [a]D + 1 1 O 0 (c 0.5 in dioxane), 238 mp ( E 15,300) (EtOH). Infrared maxima (CHC13) a t 1618, 1663, 1705, 3310, 3600 cm.-I. sir: Found: c,7'7.3; H, 8.2. The recent communication of Marshall, Riegel et (11): imp. 250", [.ID +SO" (c I ) , A,, 23s inp al.' on 11-oxygenated 17a-ethynyl,-vinyl and -ethyl (E 13,GOO). Infrared maxima a t 1605, 1692, 1602, testosterones, prompts us to publish the result of a 170'3, 3310, 3600 cm.-'. Found: C, i i . 6 ; H, 7.4. work2 on the ethynylation of steroids derivcd (111): m.p. 283", [ a ]+jjo ~ (c 0.5), Xma, 212 inp from A4-androstene-3,11,17-trione (adrenosterone), ( E 15,500). Infrared maxima a t 1615, 1663, 3310, which provides several compounds described herein, 3 6 0 @ ~ m . - ~Found: . C, 76.6; H, 8.6. whose physiological study has been undertaken in (IV): m.p. 2Sn0, [ a ]0"~ (c 0 3 ) , A,, 212 m p our laboratory. ( E 14,630). Infrared maxima a t 1606,1621, 1662, The first published 17a-ethynylated derivatives 3310,3600cm.-1. Found: C, 77.4; H, 8.2. from the 17-ketosteroids related to testosterone We have studied the effect of 3-keto-11P917@-diwere obtained by condensation of acetylene on a hydro~y-l7a-ethynyI-A~~~-androstadiene (IT') on 3P-hydroxy 17-ketosteroid, using potassium in experimental hyperlipemia and have noted its liquid a m m ~ n i a ,sometimes ~ followed by an Op- clarifying action on blood plasma. Compound IV penauer oxidation. Stavely4prepared 17a-ethynyl- was given orally to dogs (5-10 mg. 'kg.) on an hypcrA5-androstene-3,l'I-diolby condensing acetylene lipaemizing diet (10 g./kg. of milk-cream) and the in the presence of potassium tertiary amylate and blood plasma turbidity measured 3, 5 and 7 hours Inhoffen5extended this procedure to the 3,17-diones after treatment. The values noted under these whose 3-keto group previously has been protected conditions and those obtained in the Kunkel test as the enol ether. were much lomcr than the data of control series of \Ye have prepared ethynylated derivatives from dogs on the same diet, but without I V , as indicated adrenosterone6 and 3,11,17-triliet0-A~~~-androstadiin Tables I xnd 11. ene,' without protecting the 3-keto group nor making use of liquid ammonia, by condensation with TABLEI acetylene in the presence of potassium tertiary BLOOD PLASMA TURBIDITY amylate a t room temperature. The ethynylated Untreated Treated derivatives I and 11, thus obtained, lead to the cor(10 dogs) (IO dogs) Time, hr. responding 1I@-hydroxycompounds I11 and IV, by 0 0.36 0.34 reduction of the 11-keto group with borohydride, 3 1.68 .91 the 3-keto group having been protected previously 5 2.20 .85 by semicarbazide. Compounds 111 and IV may 7 1.35 .6l also be obtained by direct ethynylation of 11-dihydroadrenosterones and 3,17-diketo-l lpTABLEI1 hydroxy- A i ,4-androstadiene.7 Amax
BLOOD PLASMA TURBIDITY IN THE KUNKEL TEST Untreated
Iv (1) C. W. Marshall. J. W. Ralls, F. J. Saunders and B. Riegel, J. Bioi. Chcm., 228, 339 (1957).
(2) French Patent 1,085,464 (27-6-53) ; Belgian Patent 554,136 (French priority 13-1-56). (3) L. Ruzicka and K. Hofmann, Helv. Chim. A d a , 20, 1280 (1937); J. Kathol, W. Logemann and A. Serini, Nalurwissenschaffen, 26, 682 (1937); H. H. Inhoffen, W. Logemann, W. Hohlweg and A. Serini, Ber., 71, 1024 (1938). (4) H. E. Stavely, THIS JOURNAL, 61, 79 (1939). (5) H. H. Inhoffen and H. Koster, Ber., 72, 595 (1939). (6) T.Reichstein, Heiv. Chim. A d a , 19, 29 (1936). (7) H. L. Herzog, C . C . Payne, M. A. Jevnik, D. Gould, E. L. Shapiro, E. P. Oliveto and E. B. Hershberg. THISJOURNAL, 77, 4781 (1955). (8) M. Steiger and T.Reichstein. Ilelu. Chinz. A d a , 2 0 , 878 (1937).
Time, hr.
(10 dogs)
Treated (10 dogs)
0 3 5 7
2.40 2.53 2.68 2.62
2.30 2.12 2.12 1.72
These results seem to be related to a previous physiological study effected on adreno~terone.~ Detailed results of physiological tests will be published elsewhere. RESEARCH LABORATORIES ROUSsEL 35 BOULEVARD DES INVALIDES PARIS,FRANCE RECEIVED FEBRUARY 28, 1918
L. VELLUZ G. MULLER R. JEQUIER C. PLOTKA
(9) C. Plotka, R. Jequier and L. Velluz, Compl. rend., 244, 264 (1957).
