Silicon- Substituted Medicinal Agents.
Silacarhainates Related to Meprobaniate’
ItJis of interest. t o iiote that silicoii, i i i spitc of its :iburidaiiw o i l earth as xilicat , plays 110 discerriihl(~ role i r i innnirnnliati biochei stiy.2 .\lthough O I I P iii:iy speculate on t h e reasotis for this wo1utioii:iry disc.rimiriwtioii,~the f:ic*t iwn:tiiis t h t oi.g:tiiosilic.oii (*ompouridstire orp:tiiiv r:ithcr t 1i:iii iiiorgxiiir iit t ticir properties. T h r silic.oit-c.nrhoii tmtid is ( ( f l i t , sprii i i c*liurnctci.~ :ihout, 20% longer t1i:iri tlie ( Il-c~nrholl Ilolid, :111d the silicwn is elertroposith-e. tscqueiitly, jt ~ ~ o i i l d lw ctxpevted that tu-o organic, (wiiipouridx, n-hicah differ only in the substitutioii o f w siliiwii atoiii for I rnrboii :itom, would differ subtly i i i ;itcreoi~l-ieriii.;11.\.n r i d i l l physiral arid rlieiiiicxl properties. Thc lit(~ratui*c :rltcl our own preliiiiiiinry ~ o r l . ;arc’ suggest ivc that . i l i c ~ ) t i imnpoutids rail be used ah bioisost c i w of caarboii (winp o u ~ i d s . ~Iii order to obtniii a 1 : i i . g ~group ~ of‘ voiiipourids to evaluate such a use of sili(.oii cwiiipoiuids, wr’ have prepared and studied, i t i n preliiiiiiiatLy iiiiit1t1(’1’, 1.2 pairs of cornpouiid,aiii:itw : r i i t f wl:il t l is t h e muscale relasnitt and i,:llilate 15, Tahie ri.
iiiild
ti,:iitqtiiIin~r,i i i ~ p i ’ o -
I’iihliv liraltli Srrvire Kese i l I i x ) l‘liis research \vas siipporttvl I>>G r a n t G l I l O l 2 2 , frorn the S a t i o n a l I n s t i t u t e of General 1Iedical ,Sc,ience.*. ( b ) Presented i o the Division of JIedicinal Chewistry of tlie .iiii?ri(.an Ctiernical Society, Ctiir.ago. 111.. Sept. 1961. ( 2 ) Silicon, however, is foiind as a trace element in nearly all living inatti.1 For example, t h e silicon content of hrain t sile has heen tlie subject of a number of investigations [a. 0 . Voinar a n d K. Rusanov, B i o k h i m i y a , 14, I. Dorfman a n d S. A . S h i p i t 102 (1949): Chem. Ahstr., 43, 6719 (1949); s>-n,Biokhimi?ja, 20, 136 ( 1 9 5 5 ) : Chem. A b s t , 49, 32653 (19a5); 11,Kiillitd . , 46, 998 (1955): C h e m . ACstr.. 50, 122.52 (19Xii p r r i i i i . Bioi. i .\fed., 62, 59 (1961): Clte7i7. i l h n f r . . 66, 0257 (I962!]. (3) Tlie incorporation of the silicon is iriiportant in the plant k i n ~ c l o t i i ~ For esaniple, see 5 . 1Iitsui a n d H. T a k a t o , S i p p u n l>ojo-Hiruoouh-u %asshi. 30, ,535 (1960): Chem. Ahstr., 66, 72.7 (1962). W i t h the iiiatoili. silicun apsiinilation appears to he s n enzymatic process [J. C. Lewin. J . Gpn. I’hUu&(il., iine 37, 589 (1951): C h e m . A h s t r . , 48, 8339 (1954) 1. ~ i l i c a t ~ - c o n s ~ i ~ ihacterili h a r e alsu heen reporte(l [ % . P.Tesic a n d AI. d. ’l’,xIoroviv, % ( w t l i i s t p Bdjki, 7, 233 (1959): C h u m Ahstr.. 64, 8980 ( l 9 6 0 ) l . ( 4 ) (a) S,I’rraert arid E{. Rorsnian, .Vnturp, 192, 989 ( I W 3 ) : JZ. E’e&sen(leri aiirl AI. I). Coon, J . . l i d Chem., 7, 261 flY64). ih) T h e niajority of t l l i . Liolopical evaliiatiun of urrranosilicon rompminds has been for toxicity. l:
