Noms
4352
VOL.30
tive.6 Since it had been reported also that cleavage of methyl 3,4-anhydro-p-~-galactopyranoside in basic solution resulted in either predominant or total attack at C-3,2v4we expected to obtain methyl 3-thio-p-~MURIELDAHLQARD gulopyranoside as the main or only product. The results showed that attack did occur a t C-3, but the Department of Pharmaceutical Chemistry, College of Pharmacy, only product isolated was the sulfide, 3,3'-thiobisUniversity of Florida, Gainesville, Florida, and Department of Chemistry, Randolph-Macon Woman's College, (methyl 3-deoxy-P-~-gulopyranoside) (11), as a white Lynchburg, Virginia solid, m.p. 219-220°, along with some unreacted oxide (94% yield based on the oxide consumed). Received January $2, 1966 Proof that the sulfide I1 actually possessed a 3,3' linkage was obtained by reductive desulfuration of I1 Recently much interest has been shown in the synwith Raney nickel to give the known methyl 3-deoxythesis of carbohydrate derivatives in which an oxygen P-D-zylo-hexopyranoside (III), m.p. 175-176", which atom of a hydroxyl group has been replaced by a sulfur showed no depression in melting point when mixed atom.a We were interested in the preparation of 3with an authentic sample of I I L 4 Additional proof and 4-thiohexoses for use as possible antimetabolites was furnished by hydrolysis of the original reduction of the pentose phosphate pathway of carbohydrate mixture, followed by paper chromatography. Only m e t a b ~ l i s m . ~A , ~ possible ,~ route to such compounds one spot was detected and its Rxylose value of 1.30 was involved the reaction of sugar epoxides with hydrogen very close to the reported value of 1.33 for 3-deoxysulfide. We wish to report the results of experiments ~-xylo-hexose.~No evidence of attack a t C-4 was obin which methyl 3,4-anhydro-p-~-galactopyranoside tained. (I)was treated with hydrogen sulfide in the presence of From these results it seems probable that the initial aqueous base. attack of the HS- anion occurred a t C-3 with formation of methyl 3-thio-/3-~-gulopyranosideand that the anion CH,OH CH,OH of the latter, being a more effective nucleophile than the HS- anion, reacted immediately with a second molecule of the oxide to give the sulfide. This behavior is reminiscent of that observed with 5,6-episulOH fides, substances which polymerize in aqueous alkali.' I The sulfide I1 has also been obtained from the reaction of the oxide I with potassium thiolacetate.8 Hydrolysis of the sulfide I1 with either Amberlite CH,OH IR-120 (H+) ion-exchange resin or with 0.2 N sulfuric acid yielded 3,3'-thiobis(3-deoxy-~-gulopyranose)(V) , a white waxy solid, map.92". This substance appeared to undergo decomposition on standing; therefore, in subsequent preparations it was fully acetylated imI I mediately with acetic anhydride in pyridine and characterized as the octaacetate VI, m.p. 202-203'. When the sulfide I1 was treated with benzaldehyde in the presence of zinc chloride, a benzylidene derivative (IV) was obtained which showed a double melting point of 119-120" and 139-140" when recrystallized from benzene. This substance absorbed at 2.82 I.( in the infrared region, indicating the presence of free hydroxyl groups, and had an approximate molecular weight of 598. It could not be separated into more than one P , R = H component on a column of aluminum oxide. From the m, R = Ac elementary analysis the structure of IV appears to be the 4,6,4',6'-dibenzylidene derivative of 11, containing It had been shown earlier that the reaction of 5,60.5 mole of benzene of recrystallization. This would anhydro-l,2-O-isopropylidene-~-~-g~ucofuranose with require a molecular weight of 601 and would show abhydrogen sulfide in the presence of aqueous barium sorption at 2.82 p . Because the homogeneity of this hydroxide led to the formation of the 6-thio derivasubstance was in doubt, it was converted into the diacetyl derivative, 3,3'-thiobis(methy1 2-0-acetyl-4,6(1) This investigation was initiated a t the University of Florida with O-benzylidene-3-deoxy-P-~-gulopyr anoside) , obtained support of Grant No. CY-3885 and was continued a t Randolph-Macon as colorless needles from 95% ethanol, m.p. 259-260'. Woman's College under Grant No. CA-06314, both from the National Cancer Institute, National Institutes of Health, U.S. Public Health Service. Results of the biological testing of the compounds This support is gratefully acknowledged. described above will be reported elsewhere. (2) Part 11: M. Dahlgard, B. H. Chastain, and R. L. Han, J . O w . Chem.,
Methyl 3,4-Anhydro-P-~-galactopyranoside. 111. Reaction with Hydrogen
Hoa-
27,932 (1962). (3) See, for example, (a) E. J. Reist, D. E. Gueffroy, and L. Goodman, J . Am. Chem. Soc., 86, 3715 (1953); (b) D. Horton and D. H. Hutson, Aduan. Carbohydrate Chem., 18,123 (1963). (4) M. Dahlgard, B. H. Chastain, and R. L. Han, J . Org. Chem., 27, 929 (1962). ( 5 ) M. Dahlgard and E. Kaufmann, ibid., 26, 781 (1960).
(6) H. Ohle and W. Mertens, Ber., 8 6 8 , 2176 (1935). (7) L. D. Hall, L. Hough, and R. A. Pritchard, J. Chem. SOC.,1537 (1961). (8) M.Dahlgard, unpublished results.
Noms
DECEMBER 1965 Experimental Sections
4353
0.3 g. of a white solid, m.p. 253-256'. Recrystallization to constant melting point (95% ethanol) gave 0.24 g., m.p. 259260", [ a l z S D -24.9' ( c 2.084, CHCl,). The infrared spectrum showed no absorption band a t 2.82 p. Anal. Calcd. for C32H38012S: C, 59.44; H, 5.88; S, 4.95. Found: C, 59.33; H , 6.02; S, 5.26. 3,3'-Thiobis(3-deoxy-~-gulopyranose)(V).-A solution of I1 (2.5 g.) in 250 ml. of water was refluxed with 25 ml. of Amberlite IR-120 (H+) ion-exchange resin until constant rotation was obtained (6 hr.). The resin was removed by filtration and washed well with water. The filtrate was evaporated to a small volume and filtered through a thin mat of Norit and Celite No. 535, then taken to dryness (
