2336
BEVERLY SMITHGRIFFINAND ALFREDBURGER CONTRIBUTION FROM
THE
Vol. 78
DEPARTMENT OF CHEMISTRY, UNIVERSITY OF YIRGIVIA]
D-Glucopyranose 6-Deoxy-6-phosphonic Acid BY BEVERLY SMITH GRIFFIN'AXD XLFREDBURGER RECEIVED NOVEMBER 21, 19% The synthesis of D-glucopyranose 6-deoxy-6-phosphoiiic acid from 1,2,3,4-tetra-0-acetyl-6-bromo-6-deoxy-~-~-g~ucopyranose via 1,2,3,4-tetra-0-acetyl-~-~-glucopyranose 6-deoxy-6-(diphenyl phosphonate) has been accomplished.
I n the glycolytic process which provides energy cessful. However, when the hlichaelis-hrbuzovfor mechanical work, the creation of heat, and for methodi' was applied, compound I being heated synthetic metabolic processes, glucose-&phosphoric with a large excess of triethyl phosphite for six 6acid commands a central position. I t may be con- hours, 1,2,3,4-tetra-O-acetyl-B-D-glucopyranose verted to glucose, glucose-1-phosphoric acid and deoxy-6-(diethyl phosphonate) (111) was obtained fructose-0-phosphoric acid in ieversible reactions in near-quantitative yield. Under analogous conunder the influence of appropriate enzymes, and ditions, 11 furnished benzyl 2,3,4-tri-O-acetyl-P-Dseems to be oxidizable to 6-phosphogluconic acid glucopyranoside G-deoxy-(i-(cliethyl phosphonate) b y an alternative pathway.' Since little is known (IV). 0 about the substrate specificity of these reactions t beyond certain steric requirements of the carbohyJ3rCH2 (R'O)rPCII, drate moieties, i t was of interest t o explore the effect of structural changes of phosphorylated monosaccharides upon the biochemical behavior of such substances. A minimal structural alteration has been performed in the present study which describes D-glucopyranose-6-deoxy-6-phosphonic acid (X). 1 ; , H OAc H OAc This compound rese-nbles the metabolite, glucose-fi111, R = Ac, R' = C2H5 I, R = d c phosphoric acid, in solubility, polarity, over-a.11 It', R = CHzCsHj, R' = ClHs 11, R = CHlCaHs chemical reactivity and molecular shape but differs VI, R = Ac, R' = CsHs from i t by its inability to be dephosphorylated unV I I , R = CfI?CsHj, R ' = CsH5 der ordinary conditions. It was hoped t h a t its reV I I I , R = Ac, R ' = H IS,R = I t ' = €1 actions with glycolytic and related enzymes would shed some light on structural limitations of subThe ester I11 was also formed in lesser yields strate analogs in glycolysis. Inhibitory analogs when 1,2,3,4-tetra-0-acetyl-G-O-p-tolylsulfony1-~might, in turn, influence neoplastic growth since the D-glucopyranose12 or the corresponding methylsultumor cell derives considerable energy from rapid fonyl esterI3 were heated with triethyl phosphite in glycolysis under anaerobic and even aerobic condi- a manner described for simple alkanol arylsulfontions. ates in the recent literature. l 4 The synthesis of 6-phosphonate derivatives of Deacetylation of 111 with 0.05 iV hydrobromic glucose started from 2,3,4-tri-O-acety1-6-bromo-G- acid gave amorphous ~-glucopyranose-6-deoxy-Gdeoxy-a-D-glucopyranosylbromide (acetodibronio- (diethyl phosphonate) (V) which was characterized glucose), prepared3 by warming triacetyllevogluco- as the osazone. Hydrdysis of t h e diethyl phossan4 with phosphorus pentabrornidej in an open phonate ester group with strong acids could not be vessel on a steam-bath. Xcetodibromoglucose was effected because the products suffered decomposiconverted t o 1,2,3,4-tetra-O-acetyl-G-bromo-O-detion under these conditions. Likewise, attempts to oxy-P-D-glucopyranose (I),6 as well as to benzyl hydrolyze IV with alkali were unsuccessful although 2,3,4-tri-O-acetyl-0 - bromo - G - deovy - /3 - D - glucopy- model experiments to saponify phosphonate esranoside (11).' These compounds served as the hal- ters15s1'" using diethyl benzhydrylphosphonate availides for the subsequent introduction of the phos- able in this Laboratory" furnished low yields of phonate ester groups. The singular inertness of G- ethyl hydrogen benzhydrylphosphonate. Therehalogenoglucose derivatives recorded by earlier fure, the hydrogenolysis of glucopyranose-6-deoxyworkers,s-10 was confirmed when attempts to sub- (i-(dibenzyl or diphenyl phosphonates) appeared ject I or TI to the Kylen reaction" with sodium di- as the only feasible route t o the desired glucosealkylphosphites in hydrocarbms reniained unsuc- phosphunic acids. While benzyl and phenyl phosphate esters (1) Virginia-Carulina Chemical C,,rpornLion 17cllow. l!l,;2 -1 ( 2 ) J . S. F r u t ,n and S. Simmrinds. "(:eni.ral 13iochemistry. have been hydrogenolyzed as a means of preparing Wiley and Sons, I n c , S e w York, h ' . Y ,19,S otherwise inaccessible derivatives of phosphoric (3) J . C Irvine and J . 15'. 11. Oldham, .I. Cheiii. S a c , 127, 2729 (19231. fi) G. H . Culeman, C. hl. XcCloskey and R. K i r b y , l i z d . E i f g . Cliem., 36, 1040 (1944). ( 5 ) A. I . Popov and h-,E . Skelly, T H I S J O U R N A L . 7 6 , 3910 ('954). ( 0 ) E. Fischer, B. Helferich a n d P.Osttnann, B e r , , 63, 873 (1920). (7) E. Fischer and K. Zach, z b z d . , 4 5 , 4.56 ( 1 9 2 1 ) . (8) W. S. Mills, C h e w . 4 e n , s , 8 8 , 2 (9) B. Helferich a n d H. Collati.. B (IO) B. Helferich a n d J . F I,e?te, (11) See G. M . Rrisolapuff, "Org'inic Reactions," Vu1. V I , John Wiley and Sons, Inc., S e w York, S . Y , 19:l.
(12'1 is. 11,rrdefigrr .ind R.?,I \\li,nt;rvon, Nelz,. Chiin ilcfii, 2 9 , I I!>!? (l!l4ljl (13; 13, Hclferich, 11. Dressler and I-drogeii i r a s absorbed in 20 anol, twice with ether-methanol (1 : 1,I, and then with drbminutes, the catalyst \\-as filtered, arid the filtrate concen- ether. The yield \vas 0.1g. ( c a . 50yo,, [e]% +28.7" ( c 4.9, water). trated a t 40" in t a c u o . The residual viscous oil gave a posiAnal. Calcd. for CsH1~K70aP.H?O: C, 21.30; H , 3.87; tive Fphling test, and solidified on stirring with 3 ml. of P, 9.16. Found: C,21.56; H , 4.21; P, 9.17. pentane. It was recrystallized from ether-pentane. Th: colorless material darkened a t 175' and had m.p. 187-191 From the combined mother liquors and washings of the dec. It contained two moles of ether of crystallization potassium salt, 0.5 g. of a colorless barium salt \vas obtained xvhich could not be removed a t 110' iiz vnczio without de- with barium hydroxide, but some contaminating barium composition of the compound. carbonate could not be separated. A n a l . Calcd. for C I ~ H ~ ~ O I ~ P . ~ ( CC,~ H 46.33; I ~ O ~H:, Anal. Calcd. for C6H11Ba08P: Ba, 36.20. Found: c i . s 8 . Found: C, 46.21; H , 7.60. Ba, 3,5.47. 1,2,3,4-Tetra-O-acetyl-~-~-glucopyranose-6-deoxy-6-( b ) A solution of 0.7 g . (1.6 inmoles) of 1711in 50 1111. of phosphonic Acid (VIII).-Hydrogenolysis of 1.5 g. (0.0027 0.65 -I' hydrobromic acid was heated on a steam-hatli for mole! of \'I in 40 mi. of absolute ethanol in the pres2 hours, cooled and neutralized to p H 3 with 50 ml. of 0.63 ence of 0.15 g. of platinum dioxide waq carried out as desodium hydroxide solution. -1mixture of 1.2 g. of plienscribed in the preceding experiment. The reaction required ylliydrazine h-drochloride. 1.8 g. of anhydrous sodium from 30-90 minutes. The product (0.92 g., 76%) crystalacetate : ~ n d1 nil. of a saturated sodium bisulfite solution lized slowlyfrom absoluteethanol, m.p. 171-178' dec., [eja5, was added, and the whole heated at 95' for 2 hours. X '9.5' (c 3.27, chloroform). I t wa? dried a t 66" over someirhat gelatinous j-elloir precipitate appeared on cooling. phosphorus pentoxide. I t \vas recrystallized from 75yo ethanol to melting point Ann?. Calcd. for ClaH,101?I-'~2H~O: C, 37.30; H, 5.62. 162-169', and purified further by sublimation a t 65" (1.,5 Found: C, 37.83; H , 5.77. X mm.). The osazone melted a t 170-172°. Further drying a t 78' for four days removed all but 0.5 Anal. Calcd. for C18H23X40GP: S,13.27; neut. equiv., mole of water of crystallization. 422. Found: S,12.63; neut. equiv., -E%.?' ___ A i d . Calcd. for C14H21012P.L/?H?O: C, 39.91; H , 5.27. (24) T h e analyses nf this osazone were performed b y Dr. C h Found: C, 39.94; H, 5.01. The acid gave a lead salt insoluble in Jr-ater, and a some- bourne E. Griffin. \\-hat water-soluble barium salt. CHARLOTTESVILLE. VIRGISIA
COMMUNICATIONS T O T H E EDITOR NEW SYNTHETIC CRYSTALLINE ZEOLITES
Sir: T h e outstanding characteristic of some natural hydrated zeolites is their ability to undergo removal of water of crystallization with little or no change in crystal structure. T h e dehydrated crystals are then interlaced with regularly spaced channels of molecular dimensions in which adsorption may occur. Because of the interesting adsorptive properties of these rare natural minerals, a research program was initiated in this laboratoq in 1949 t o study the synthesis and properties of zeolites. Between 1949 and 193, twenty crystalline zeolites mere synthesized. These included. synthetic counterparts of the minerals chabazite, gxnelinite, erionite, and mordenite, a species very similar to gisxnondite, and a species isostructural with faujasite but quite different in chemical composition. I n addition, fourteen zeolite species were synthesized which have no natural counterparts knowii to LIS. These new synthetic zeolites have been the subject of intensive study in this and other baboraiories, and a number of papers describing their properties in detail will appear shortly.
Chemically, these zeolites may be represented by the generalized formula : Mex,%[ (AlO2),(Si02),]. MHzO, where x / n is the number of exchangeable cations of valence n, and df is the number of water molecules, removal of which produces the characteristic pore system. One of the new synthetic zeolites, designated as zeolite "X," which has no known natural counterpart has the composition: Me12/%[(A102)12(Si02)1?. 27H20. iXrhen M e is S a + or Ca'f the adsorption volume is about 0.30 cc. per gram of dehydrated zeolite. IVhen M e is ?Ja+ the dehydrated 7 6 0 lite readily adsorbs molecules having a critical dimension up t o 4 A., the critical molecular dimension being defined as the diameter of the smallest cyliiider which will accommodate a model of the molecule constructed using the best available van der n'aals radii, bond angles, and bond lengths. U%en of the sodium ions are exchanged for calcium ior,s, the effective pore dianieter increases to about c5A. For example, straight-chain hydrocarbons are adsorbed readily whereas branched-chain hpdrocarbons are excluded. Iieplacenient of sodium by potassium decreases the effective pore diameter. These and other phenomena are explained on the
