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COMMUNICATIONS TO THE EDITOR
Vol. 85
From this assignment, it follows directly that the Acknowledgments.-This investigation was supabsolute stereochemistry of deoxystreptamine in neported in part by research grant No. E-1278 from the amine is as shown in Ie. The neamine component of National Institute of Allergy and Infectious Diseases, neomycins B and C is identical and substituted deoxyPublic Health Service. We also wish t o express our streptamine structures If and Ig may be written for thanks to the Upjohn Company for neomycin samples, the antibiotics themselves. Since Ib is also obtained to Mr. W. S . Chilton for assistance in carrying out some from poly-0-methyl-penta-N-acetylparomomycin, 3a and of the experiments and, particularly, to Professor Gabor from the poly-0-methyl-N-acetyl derivatives of zygoFodor, who, during discussions in Budapest, raised the mycins AI and A23b(probably identical with paromomypossibility of application of Reeves' method to this cins I and 11), the substituted deoxystreptamines in problem. these antibiotics are I h for paromomycin-zygomycin AI, DEPARTMENT OF CHEMISTRY ASD CHEMICAL EKGISEERING OF ILLINOIS MARTINHICHENS UNIVERSITY and probably Ii for paromomycin 11-zygomycin A2. URBANA, ILLINOIS KENNETH L. RINEHART, JR. Moreover, the very recent isolation of paromamine8 RECEIVED OCTOBER 24, 1962 [Ij; 4-(2-amino-2-deoxy-a-~-glucosy~)-deoxystreptamine] from partial hydrolysis of kanamycin C9 estab1,1,1,4,4,4-HEXAFLUORO-2,3-DIPHENYL-2,3-BUTANEDIOL lishes the absolute configuration of deoxystreptamine in that antibiotic'" as in Ik. Also, since kanamycins Sir : A" and B,12 like kanamycin C,l0 contain kanosamine We wish to report the observation of a remarkable re(3-amino-3-deoxy-~-glucose) and deoxystreptamine, but sistance to pinacol-pinacolone rearrangement exhibited differ from kanamycin C in the replacement of its by a symmetrical alkyl aryl ethanediol. glucosamine fragment by 6-aminoglucose in kanamycin 1,1,1,4,4,4-Hexafluoro-2,3-diphenyl-2,3-butanediol (I) A and by an unidentified diaminohexo~e'~(on biowas prepared in 17y0 yield by the photopinacoligenetic grounds this should be neosamine C) in kanazation reaction between 13 g. of trifluoromethyl mycin B the absolute stereochemistry of deoxystrepphenyl ketone' and 75 ml. of 2-propanol in a quartz tamine in these antibiotics is almost certainly as in tube a t 5 cm. from a Hanovia 16A-13 mercury vapor 11 and Im, respectively. lamp. Distillation of the solvent and recrystallization With the assignment of this last stereochemical of the residue from 80 : 20 hexane-ether produced 2.16 point the structure of neomycin C is completed and g. of white needles. These were further purified by submay be written as shown. limation in vacuo; m.p. 155-156O. ( A n d . Calcd. for Cl6Hl2O2F6:C, 54.86; H, 3.45. Found: C, 55.10; H , CHzNHz 3.38.) HO The compound possessed an infrared spectrum, in KBr disk, completely consistent with its assignment ps Deoxystreptamine the pinacol: -OH, 3440-3600 cm.-'; -CF3,2 11651210 cm.-'; and the complete absence of carbonyl absorptions. O+NH~HO Oxidative cleavage of I with lead tetraacetate in boiling acetic acid gave only trifluoromethyl phenyl ketone, identified as its 2,4-dinitrophenylhydrazone : m.p. and HO mixture m.p. 108-109°; literature m.p. 106-107°.3 The pinacol was found to be completely resistant to Neosamine C >Ribose several concentrations of sulfuric acid in acetic acid a t rieornycin C steam bath temperatures. It could be recovered unchanged from 38y0 sulfuric acid after 4 hr. heating and Complete structures of neomycin B and paromomycin from 65% sulfuric after 6 hr. heating. I t resisted the await further evidence for the stereochemistry of neoaction of boiling acetic acid-0-naphthalenesulfonic acid samine B. The cuprammonium method provides for 30 hr. further evidence on this point, as well. As expected, The non-fluorinated analog of I , 2,3-diphenyl-2,3a high positive increment is observed in the rotation of b ~ t a n e d i o lprepared ,~ by the addition of excess methylmethyl N,N'-diacetyl-a-neosaminide C (a 2,6-diaminolithium to benzil, could be transformed into 3,3-diphenD-glucose derivative, with free hydroxyl groups a t C-3 yl-2-butanone by much less vigorous conditions: 0.6% and C-4) in cuprammonium B solution; A [ M ] ~ u p r aB p-toluenesulfonic acid or O.670 iodine in acetic acid = +2280". Of greater significance is the strong positive after 0.5 hr. reflux. increment of methyl N,N'-diacetyl-a-neosaminide B ; The resistance of I to acidic conditions substantially A [ M l ~ u p r aB = 1880". Though this observation does in excess of those required to rearrange similar diols may not of itself exclude L-talose or L-altrose stereochemistry be interpreted as a destabilizing influence of the powerfor neosamine B, it does exclude the five other isomers fully electron attracting trifluoromethyl group to the allowed by neosamine B's stereochemistry a t C-214,l 3 development of carbonium character on the hydroxyl(with the amino group on the right in the Fischer probearing carbons. Such carbonium character is generally jection formula) and is most consistent with the previously suggested2 2,6-diamino-2,6-dideoxy-~-idoseagreed to be a prerequisite to the rearrangement step.5 DEPARTMEXT OF CHEMISTRY WILLIAM X MOSHER stereochemistry. ~
HoGyH +
(8) T . H . Haskell, J. C. French and Q. K. Bartz, J . A m . Chem. S o r . , 81, 3480 (1959). (9) T. Wakazawa and S. Fukatsu, J. Anlibiolics (Tokyo), S e r . A , 16, 225 (1962). (10) M. Murase, ibid., 14, 367 (1961). (11) M. J. Cron, D. L. Evans, F. M. Palermiti, L). F. Whitehead, I . R . Hooper, P. Chu and R . U. Lemieux, J . A m . Chem. SOL., 80, 1742 (1968). (12) H . Schmitz, 0. B . Fardig, F. A. O'Herron, M. A. Rousche and I. R . Hooper, ibid., 80, 2912 (1958). (13) I. R. Hooper, personal communication. (14) K . L. Rinehart, Jr., A. L). Argoudelis, T . P. Culbertson, W. S. Chilton and K . Striegler, J . A m . Chem. Soc., 82, 2979 (19fiO). (15) T. H. Haskell, J. C. French and Q.R . Bartz, ibid., 81, 3181 (1959).
UNIVERSITY OF DELAWARE NEDD . HEINDEL~ XEWARK, DELAWARE RECEIVED MARCH 21, 1963
(1) The ketone was synthesized according t o the procedure of A . Sykes, J . C. Tatlow and C . R . Thomas, Chem. I n d . (London), 630 (1955). (2) I n agreement with previous spectral investigations of the -CFa group, an intense absorption band consisting of a series of multiple peaks is observed: 1.. J . Bellamy, "The Infrared Spectra of Complex Molecules," 2nd. Ed., John Wiley and Sons, Inc., New York, N. Y . , 1958, p. 330. (3) A . Sykes, J . C. Tatlow and C . R . Thomas, J . Chem. Soc., 835 (1956). (4) I). Cram and K . Kopecky, J . A m . Chem. SOL.,81, 2748 (1959). (5) J . F . 1)uncan and K. R . Lynn, Auslralian J . Chem., 10, 7 (1957). ( 6 ) N . S . F . Coiiperative Graduate Fellow, 1959-63
