Totally Synthetic Steroid Hormones. T.II.' Some (&)-8a-Estrane and (+)-13p-Alky1-8a-gonane Derivatives
13. GADSBY, A N D A. 13. A. .J.ZXSF,N John lV?/dh ck Hrolher Lld., Huntercornbe Lane South, l'nploir, JlnirlPnhPod,
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.I heries of ( ~)-13P-:ilkyl-80c-gona-l,Y,3( lO)-trieiie> of 1ypes 4 arid 5 lias been totally synthesized for iiivctstigation as possible nonfeminizing, lilood lipid lowering agents. The (I-t)-alcohols ( 5 , 11. = CH3 and C a 1 I 6 ; = €1) have been converted to the corresporiding ketones (10, It = CH, and C2H,; 1:' = C=CIf), required for birhgiral evalriation. i-arious biological activities of these campiiriiids are briefly described.
Reports of t,he cxorisiderable retent,ion of hormonal :i,ctivities b y an ( f)-cst.rone st'ereoisomer, subsequently shown to be (+)-8c~-estrone,~ and by 8aprogesterone5 and 8a-testost,erone5 prompted us to (:stend the synt,het.ical methods described in earlier to prepare a variety of related ( + )-estrane :md ( =t)-13/3-alkylgonanc derivatives for biological cvaluat'ion. A pa,rt of the work relating to the ring A :rromatio members of our series has already appeared in t,he pat,entliterat'u~e.~ (=1=)-8a-Estra-l,3,5(1O)-trienes and (+)-8a-Gona1,3,5(10)-trienes.---Re have shown that the (+)cstrapent,aenes (1, It = CH,; R1= H, CHs, and CH,C0)687 give predominantly t,he corresponding Sacstratsiencs (4) Inby cat:tlytic hydrogenation in ethanol over a pdlzidium rntalyst, arid that t,he estrapentaerie (1, R = R * = CIS,) arid the gonapentaenes (1, R = ('.H6 and n-CRH7; R' = CH,) give t8hecorresponding t.c%raencsof class 7 by s i m h r hydrogenation in benzen(~.G-s Accordingly, we could a s u m e t,hat, t,he palladium-catalyzed upt'ake of 2 moles of hydrogen by t,he pcntaenes (1, 2% = C&; R1 = H, CH,, and CH,CO) nould lead to the corresponding 8a-gonatrienes. The goriatriene formulated as 4 (R = C2H5;R' = CH,) is obtained from t h e ketone 1 (R = C2H5; R' = CH,) hy this process, and from it,s cyclic et'hylene ketal 3 (It = CzH5; Rl = CHa) by cat,alytic hydrogenattion :md :wid hydrolysis. Sodium borohydride convert's the lict,one 4 (R = Rl = CH,) into an alcohol (5, It = li.1 = (:Ha) shown t,o be a lip-ol from its identity with (1) Part V I : G. €1. I)ouglas, G . C. 13uzby. ,lr., C. R . \Talk, a n d H . Smith, Tetrahedron, in press. 12) T o &om inquiries concerning this paper should be addressed. (3) G. .\nner a n d K . hfiescher, Helu. C h i m . Acta, 32, 1957 (1949). (4) LV, S. Johnson, I. .iDavid, . H. C. Dehm, R . J. Highet, E. W.Warnhoff, TV, D. \Vood, and E. T. Jones, J. Am. Chem. Soc., 80, 661 (1958). (5) C. Ijjerassi, 1.J. Manson, and H. Rendas, Tetrahedron, 1, 22 (1957). [ ( j j G. A. Hughes and H. Smith, Chem. I n d . (London), 1022 (1960). ( i ) G. 13. I>ouglas, J. If. II. Graves. I). Hartley, G . A. Hughes, E. .I. .\Irl,oughlin, J. Siddall, and H. Smith, J . Chem. Soc., 5072 (1963). ( 8 ) ( a ) H. Smith, et d.,E z p e r w n l i a , 19, 894 (1963); (b) H. Smith, el al., .I. C h ~ m Sor.. . 4472 (1964). ( 9 ) G. A . Hughes and H. Smith, Belgian Patent 600,i59 (1R61: p r i o r i t y f r o m February 29, 1960). ( I O ) T h e structural formulas depict t h e enantiomer having t h e 1:i-alk.vI g r < > i i pin the 6 configuration.
that formed by hydrogenating thc tc~tr.:wtw 8 (It = I
