Vol. 69
COMMUNICATIONS TO THE EDITOR
1.530
a similar procedure and shown to be identical with acid (kept neutral with sodium carbonate) to prothe higher-melting isomer B from streptomycin B duce phenyl iodide and S-phenylthioglycolic acid by melting point (161-162", no depression on ad- (21'7, yield), m. p. 58-60' (lit. G1-63°2); sparingly mixture of isomer B), rotation ( [ a ] 2 5 -65' ~ (c, soluble in water, soluble in benzene. This reac1.1 in chloroform)), and analysis (C, 49.19; H, tion is a rapid one a t the boiling point of the solu5.98; S, 8.41; CHaCO, 44.7). The dextrorota- tion. It also proceeds a t room temperature but a t tory isomer A from streptomycin B presiimably a reduced rate. When thioglycolic acid dissolved represents the previously unknown anomeric a- in water is shaken with diphenyliodonium chlothioethyl-tetracetyl-D-mannoside. ride, sodium carbonate, tellurium and ether a t Dihydrostreptomycin B trihydrochloride', m. room temperature, diphenyltellurium is formed. p. 194-5' (cor. dec.), [a]''D -55' (c, O.gin.water), The latter compound can be isolated from the on treatment with 3% methanolic hydrogen chlo- ether layer as the yellow dibromide, m. p. 199ride for forty hours at room temperature and sub- 800'. The reaction with tellurium is an interestsequent acetylation yielded a-methyl pentaacetyl ing one because of the possibility of a free radical dihydrostrept~biosaminide~J m. p. 192-3' (cor.), mechanism, although other interpretations are [ a I z 5 -119' ~ (c, 0.40 in chloroform) and 8- possible. methyl tetraacetyl D-mannopyranoside, [ a1 I t has also been found that diphenyliodonium -50' (c, 0.69 in chloroform), m. p. 160-161" chloride reacts with other thiol compounds, such (cor.), unchanged on admixture of an authentic as thiophenol and cysteine. In the latter case the specimen. product is S-phenylcysteine, m. p. 200' (lit. 201Anal. Calcd. for C15H22010: C, 49.72; H, 202°)4; calcd. for C9HI102Sr\;: S,16.3. Found: 6.12; OC&, 8.56; CHaCO, 47.5. Found: C, S, 16.2. All the iodonium reactions show a characteristic transient yellow color or precipitate. 49.61; H, 6.08; OCH,, 8.35; CH&O,48.5. The above reactions should be of interest from These results together with analytical data previously reported' for the reineckate' and hydro- the standpoint of enzyme studies. Further work chloride of streptomycin B indicate that streptomy- is in progress and we hope to communicate full cin B is made up of streptidine, streptobiosamine details a t a later date. We are very grateful to and D-mannose joined glycosidically to forin a the Alberta Branch of the Canadian Cancer Sotriacidic base of the composition Cz7H~~017N7.ciety for financial aid in support of this work. DEPARTMENT OF CHEMISTRY REUBENB. SANDIN Anal. Calcd. for C27H4901iNi.3HCr[("3)2 ROBERT G. CHRISTIANSEN (SCN)4]*2HzO: C, 26.97; H, 4.29; N, 20.15; UNIVERSITY OF ALBERTA ROBERT I(.BROWN S, 22.11; Cr, 8.98. Found' (after drying itz vacuo ED'MONTON, C S S A D A SAMUEL KIRK\VOOD5 a t SOo for two hours): C, 26.89; H, 4.24; N, RECEIVED MAY14, 1947 20.1; S, 22.2; Cr, 8.70. Calcd. for C27H4901i- (2) Gilman and Webb, THISJ O U R N A L62, , 987 (1940). Nj.3HCl.HzO: C, 37.26; H, 6.24; N, 11.23; (3) Sandin, h l c c l u r e a n d Irwin, THISJOURNAL, 61, 2!)44 (1939); C1, 12.23. Found (after drying in vacuo at 140' Sandin a n d Brown, unpublished work. ( 4 ) Clarke and Inouye, J . B i d . Chem., 94,541 (1931). for two hours): C, 36.85; H, 6.11; N, 11.3; ( 5 ) Prrsent address: 201 Prospect Avenue. Princeton, New c1, 13.83. Jersey. f 4 ) J. Fried a n d 0. Wintersteiner, THISJOURNAL, 69, 79 (1947). (5) 0.R. Bartz, J. Controulis, H. M. Crooks, Jr., and M . C. Kebstock, ibid., 68, 2163 (194F).
FURAN AND TETRAHYDROFURAN DERIVATIVES. DIVISIONOF ORGANIC CHEMISTRY JOSEF FRIED VIII. THE SYNTHESIS-OF THE SULFONIC- ACID THESQUIBB INSTITUTE FOR MEDICAL RESEARCH ANALOGS OF OXYBIOTIN AND HOMOOXYBIOTIN ,YEW BRUNSWICK, NEWJERSEY HOMERE. STAVELYSir: RECEIVED MAY19, 1947
sir:
THE REACTION OF IODONIUM SALTS WITH THIOL COMPOUNDS
In the interesting paper by Freedlander and French' on the chemotherapy of certain ioclonium compounds, they have suggested tentatively that the activity of the iodonium compounds may, in some cases, be due t o a reaction with certain thiol groups essential to the microorganisms. For some time we have been engaged in the study of the reactions which occur between iodonium salts and sulfhydryl compounds. We have found, for example, that diphenyliodoniuni chloride reacts in an aqueous solution with thioglycolic (1) Freedlander and French, Proc. (1946): C. .4.. 41, 2115 (1947).
5'06.
E a p f l . B i d . M e d . , 63, 319
In connection with our studies on the relationships of chemical structure and biological activity in the biotin and oxybiotin series,' we became interested in dl-oxybiotin sulfonic acid (I) and dlhomooxybiotin sulfonic acid (11), the sulfonic acid analogs of dl-oxybiotin (111) and dl-homooxybiotin (IV), respectively. I n this communication we wish to record the synthesis of these two compounds.
co HS/
\EH
(1) Hofmann, Chen, Bridgwater a n d Axelrod,
191 (1947).
n
R
THISJOURNAL,69.
June, 1947
COMMUNICATIONS T O T H E EDITOR
1551
FISSION OF BETA-OXYGENATED dl - Hexahydro - 2 - oxo - 4 - (4 - hydroxybutyl)ORGANOSILICON COMPOUNDS l-furo-(3,4)-imidazole (V), m. p. 154-155' (Anal. Sir : Calcd. for CgH1603N2: C, 53.98; H, 8.05; N, Gilman and Clark in THISJOURNAL, 69, 967 13.99. Found: C, 54.12; H, 7.81; N, 13.80) was obtained from 2-furanbutano12 (cr-naphthyl- (1947)) quite naturally assume that the formation urethan, m. p. 72-73'; Anal. Calcd. for ClgH1g- of acetone from the reaction product of triethyl0 3 N : C, 73.76; H, 6.19; N, 4.53. Found: C, chlorosilane and sodioacetoacetic ester proves the '73.82; H, 6.17; N, 4.71) by the procedures de- absence of EtaSiCH(COCH3)COzEt. While that veloped in these laboratories for the synthesis of substance is likely absent, many studies in progsimilar corn pound^.^^^ Treatment of (V) with ress in this Laboratory on related /?-oxygenated thionyl chloride gave dl-hexahydro-2-oxo-4-(4-silicon compounds convince us that their reaschlorobutyl)-l-furo-(3,4)-imidazole (VI), m. p. oning is unsafe. Thus, we find that reactions 124-126' (Anal. Calcd. for CgHljOzN2C1: C, expected to form R3SiCH2COCH3and R3SiCH249.38; H, 6.90; N, 12.80; C1, 16.22. Found: C02H actually give acetone and acetic acid, reC, 49.16; €I, 6.84; N, 12.54; C1, 16.27), which on spectively. Moreover, R3SiCH2CHOHCH3 is reaction with sodiobenzyl mercaptide was con- sensitive to acid, giving propylene readily. In verted into the corresponding benzyl thioether each case most of the silicon appears as (R3Si)ZO. (VII), m. I). 76-79' (Anal. Calcd. for C16HZ2O2- Acetyl chloride and the Grignard reagent (I) N2S: C, (52.73; H, 7.24; N, 9.14; S, 10.46. from chloromethyltrimethylsilanelgave a yellow Found: C, 62.54; H, 6.96; N, 9.31; S, 10.32). solid which, on decomposition with water, formed Reductive cleavage of (VII) yielded dl-hexahydro- a variety of products including acetone. The latter was identified by conversion to dibenzal2 - oxo - 4 - (4 - mercaptobutyl) - 1 - furo - (3,4)- acetone, m. p. and mixed m. p. 111-113'. imidazole (VIII), which on oxidation with barium Addition of carbon dioxide to (I) formed a colpermanganate was converted into the crystalline orless gel which, on steam distillation, gave hexabarium salt. of oxybiotin sulfonic acid (I). (Anal. methyldisiloxane. The residue was acidified with Calcd. for C9H1505N2SBa/2: C, 32.53; H, 4.55; dilute sulfuric acid and steam distilled. The disN, 8.44; S, 9.66; Ba, 20.69. Found: C, 32.58; tillate smelled strongly of acetic acid. This was H, 4.74; N,8.18; S, 9.43; Ba, 20.33.) The con- identified as the p-phenylphenacyl derivative, m. figuration of (I) must be identical with that of dl- p. 110-11l0. oxybiotin (111), since (VI) upon reaction with Acetaldehyde and (I) gave P-hydroxypropyltripotassium cyanide followed by hydrolysis gave methylsilane, b. p. 48' a t 10 mm., nZoD 1.4281. (111). Anal. Calcd. for C6Hl6SiO: Si, 21.2. Found: Similarly, dl-homooxybiotin sulfonic acid (11) Si, 2.4. Warming with a few drops of 10% sulwas prepared from dl-hexahydro-2-oxo-4-(5- furic acid gave a stream of gas which was conchloropentyl) -1-furo-(3,4)-imidazole' through the verted to propylene dibromide, b. p. 139' a t 728 corresponding benzyl thioether (IX), m. p. 66-68' D mm., ~ z ~ O 1.5196. Other studies point to similar conclusions on the (Anal. Calcd. for C17H2402N2S: C, 63.73; H, sensitivity to hydrolytic agents of the grouping i . m ; N, 8.74; S, 10.00. Found: C, 63.24; H, in which the last two atoms may be 7.36; N, 8.89; S, 10.30), and the mercapto- Si-C-C-0 pentanol (X). .is in the case of the lower singly or doubly bound in alcohols, ketones, acids, homolog (11) was also isolated in the form of esters and the like. The resulting fissions are not its crystalline barium salt. (Anal. Calcd. for surprising in view of the ease with which silicon CI0H17O5N2SBa/2: C, 34.70; H, 3.95; N , can give an electron pair to an electronically de1.10; S, 9%; I3a, 19.86. Found: C, 34.37; ficient carbon atom in the position beta to it.* (1) Whitmore and Sommer, THISJOURNAL, 68, 481 (1D4G). H, 5.20; N, S.14; S, 9.30; Ba, 19.60.) Com(2) Cf.Whitmore, rbrd , 64, 3277 (1932); 55, 4153 (1933), Sompounds (I), (VII), (VIII), (IX), and (X) were mer, et aE , ibid., 68, 1083 (1946). found to have pronounced antibiotin and antiSCHOOL OF CHEMISTRY F. C. \I"ITMORE oxybiotin activity for a number of microorganA N D PHYSICS L. H. SOMMER isms, in contrast to substance (11)) which had PENNSYLVANIA STATECOLLEGE JACKGOLD PA. R. E. \-AN STRIEN a slight stimulatory effect. A detailed descrip- STATECOLLEGE, RECEIVED MAY13, 1947 tion of the synthesis and microbiological activity of these coinpounds will be presented in the near future. SYNTHESIS OF PROTEIN ANALOGS r
--
Sir: I~EPARTMENT OF CHEMISTRY KLAUSHOFMANN We wish to record what we believe to be the UNIVERSITY OF PITTSBURGH, ASD ANNABRIDGWATER THE INSTITUTE O F PATHOLOGY WESTERN PENXSYI,V.4SIA HOSPITAL A. E. AXELROD first successful synthesis of molecules having, like fibrous proteins, the structure PITTSBURGIT, PA. RECEIVED MAY9, 1947 HOOC-CH(RI)-SH-(COCH(R,) NH),,-COCH (Rs,+ 1 ) KHz I 12) Hofmann, Bridgwater a n d Axelrod, unpublished resiilts. (3) Hofmann, TIXIS JOIJRNAL: 67, 1459 (1945).
with very large values of n.
