NOTES
3440 Inclusion Compounds of Carbohydrates and Related Compounds’ HARMON L. HOFFMAN, JR., GEORGER. BREEDEN, JR., AND R. WINSTON LIGGETT Southern Research Institute, Birmingham, Alabama Received January 29, 1968
Inclusion compounds have attracted considerable attention in recent years, and an inclusion mechanism has been suggested as an explanation for the occurrence and the specificity of certain organic reactions, particularly enzymic reactions.2 However, the inclusion of carbohydrates in such compounds has apparently not been studied, and this investigation was undertaken to explore the possibility that, if inclusion compounds of carbohydrates are formed, the inclusion would affect the reactivity of the carbohydrates. It was found that carbohydrates and some related compounds can be included in crystals of Dianin’s compound (4-phydroxyphenyl-2,2,4-trimethylchroman) 3 and in 0cy clodextrin. The inclusion compounds were best prepared by a method in which the guest and host compounds were dissolved and the inclusion compound was crystallized from the solution. Table I shows examples of host and guest compounds, solvents, and yields and compositions of the inclusion compounds. The presence of each included compound was demonstrated by paper chromatography, and, except for L-ascorbic acid, the amount was determined quantitatively by an appropriate method. TABLE I INCLUSION OF CARBOHYDRATES AND RELATED COMPOUNDS
Host
Dianin’s compound
D-Glucose
Solvent
Yield of inclusion compd., %“
1 N NaOH
100
Guest content,
%
4
1 N NaOH 100 8 Glycerol DMFb 100 3 Sorbitol DMF 14 5 n-Glucose pentaacetate 100 11 Pyruvaldehyde 2 N NaOH 90 5 Dihydroxyace- Decalin tone 100 4 Dihydroxyace- Decalin tone diacetate DihydroxyaceDecalin 90 14 tony1 acetonide 95 2c >Ascorbic acid 1 A: NaOH HzO 46 8 p-Cyclodextrin D-Glucose HzO 85 7 Glycerol HnO 41 2 Sorbitol Dimethylformaa Weight 70 of starting host compound. mide. Estimated from paper chromatograms. (1) This investigation was sponsored by the United States Army Research Office ( D u r h a m ) . (2) F. Cramer, Angew. Chem., 66, 320 (1953); Ber., 86, 1576 (1953); W. Lautsch, W. Rroser. W. Biedermann. and H. Gnichtel, Angew. Chem., 66,123 (1954). (3) A . P. Dianin, J . R u s s . P h y s . Chem. S O C . ,46, 1310 (1914); Chem. Zentr., I, 1063 (1915)
VOL.29
D-Glucose (lye) was included preferentially by Dianin’s compound in a diniethylformaniide solution containing equal amounts of D-glucose and sorbitol, and glycerol (3%) was included in preference to Dglucose. Attempts to include glycerol, D-glucose, and D-glucose pentaacetate in the Werner complexes, tetrakis(Pmethy1pyridino)nickel dithiocyanate, tetrakis(4-ethy1pyridino)manganese dithiocyanate, and tetrakis(4-methy1pyridino)cobalt d i ~ h l o r i d e were , ~ unsuccessful. The largest quantity of glycerol (8%) included in Dianin’s compound represents about 1 molecule/ Dianin cage which has been estimated: from X-ray diffraction data to be 27 A. high and 11 A. in diameter at the narrowest part. The inclusion compounds of the larger carbohydrates contained an average of 1 molecule/3-6 cages. p-cyclodextrin might be expected to include a maximum of 12% of D-glucose to correspond to 1molecule/dextrin ring. I n some cases, the inclusion of the carbohydrate rendered complete protection from oxidative attack. I n other cases, it seemed that the oxidation proceeded more slowly. Glycerol included in Dianin’s compound, for example, was not attacked by hydrogen peroxide or lead tetraacetate. However, oxidation occurred if periodic acid was used. I n contrast, both sorbitol and D-glucose were protected from oxidation by periodic acid but were attacked, a t least to a certain degree, by hydrogen peroxide and lead tetraacetate. pCyclodextrin with its more open structure offered less protection, as is indicated by the fact that no essential difference between oxidation of included and unincluded carbohydrates could be observed. Experimental Preparation of Inclusion Compounds.-The host and the guest materials were dissolved with heating in the solvent indicated in Table I and the inclusion compound crystallized from the solution on cooling to room temperature and standing for a few hours. When sodium hydroxide solution waa used as the solvent, the solution was neutralized to induce crystallization. Adherent materials were removed from the crystalline inclusion compounds by washing them with suitable solvents. The crystal habit of the host usually was not changed by inclusion of the guest, but when sorbitol was included in Dianin’s compound, the crystals were changed from a fine powder to chunky needles. Identification and Analysis of Included Materials .--D-Glucose, sorbitol, glycerol, L-ascorbic acid, pyruvaldehyde, and dihydroxyacetone were identified qualitatively by descending paper chromatography on Whatman No. 1 paper. The irrigant w a ~1butanol-ethanol-water (40: 11: 19, v./v./v.). The presence of carbohydrates on the chromatograms was demonstrated by development with silver nitrate, which also produced a spot due to Dianin’s compound, but not with p-cyclodextrin. D-Glucose, L-ascorbic acid, pyruvaldehyde, and dihydroxyacetone were identified with aniline hydrogen phthalate as the developer. Sorbitol and glycerol were identified with the aid of bromocresol purple borate as the developer.e Various procedures were used for the quantitative determinations of included carbohydrates. Reducing compounds, for example, D-glucose, pyruvaldehyde, and dihydroxyacetone, were
(4) W. D. Schaffer, W. 9. Dorsey, D. A. Skinner, and C. G. Christian, J . A m . Chem. Soc., ’IS,5870 (1957). (5) H . M. Powell and B. C. P. Wetters, Chem. Ind. (London). 256 (1955). (6) R . H.Hackman and V. M. Trikojus. B i o c h e n . J . , Si, 653 (1952).
NOTES
NOVEMBER, 1964 determined by the Lane-Eynon copper-reduction method.? DGlucose pentaacetate and dihydroxyacetone diacetate included in Dianin’s compound mere determined by analyzing the inclusion compound for acetyl content according to the method of Green and Perkin.6 Dianin’s compound did not interfere in either of these analyses. Glycerol and sorbitol included in a host were determined by analysis of the products from periodic acid oxidation of the carbohydrategafter the inclusion compounds were dissolved to release the carbohydrate. The amount of the dihydroxyacetonyl acetonide included in Dianin’s compound was determined by the weight increase of the host compound. The quantity of 1.-ascorbic acid included in Dianin’s compound was estimated by comparison with known quantities of L-ascorbic acid on paper chromatograms. Oxidation.-The inclusion compounds of D-glucose, sorbitol, and glycerol with Dianin’s compound and of sorbitol and glycerol with (3-cyclodextrin containing from 0.0003 to 0.01 mole of carbohydrate were suspended separately in about 10 ml. of water. Ferrous sulfate (0.0001 g. for Dianin’s compound and 0.005 g. for (3-cyclodextrin) and hydrogen peroxide in mole ratios of 1 : 1 and 1: 10 (hydrogen peroxidecarbohydrate) were added to the slurry. The mixture was stirred for 1 hr. and then allowed t o stand for 3 hr. a t room temperature. The crystalline material was collected by filtration, washed with water, and dried. Solutions and solids were examined chromatographically using butanol-ethanol-water (40:11: 19, v./v./v.) as the irrigant. Most inclusion compounds produced oxidation products identical with those obtained from oxidations of the corresponding unincluded carbohydrates under the same conditions. Only glycerol included in Dianin’s compound was unaffected. Slurries (in dilute acetic acid) of n-glucose, sorbitol, and glycerol included in Dianin’s compound were treated with lead tetraacetate following the procedures of Perlin and Brice.lo Oxidation occurred only with D-glucose and sorbitol but not with glycerol a~ was indicated by paper chromatographic examination of the oxidation product. Oxidation of carbohydrates included in Dianin’s compound and in 8-cyclodextrin with periodic acid were carried out according to a procedure of Miner and Dalton.g The formic acid produced was determined quantitatively and considered as an indication of the extent of oxidation. (7) (a) J . Lane and L. Eynon, SOC.Chem. Ind. (London), 42, 3 2 ~ 1, 4 3 ~ , 4 6 3 ~(1923); 44, 1501 (1925); 46, 4 3 4 ~(1927); SO, 851 (1931); (b) “Polarimetry, Saccharimetry, and t h e Sugars.” Circular C-440, United States Government Printing Office, Washington, D. C., 1942, p. 185. (8) A. G . Green and A. G . Perkin, J. Chem. SOC.,89, 811 (1906). (9) S. Miner and N. Dalton, “Glycerol,” American Chemical Society Monograph 117, Reinhold Publishing Corp.. New York, N. Y . , 1953, pp. 187-193. (10) A. S. Perlin and C. Brice, Can. J. Chem., SS, 1216 (1955).
Studies on the Alkaloids of Securinega virosa Pax. et Hoffm. IV.’ The Preferred Conformations of Allosecurinine (Phyllochrysine) and Dihydrosecurinine T. NAKANO, T. H. YANG,AND S. TERAO Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, J a p a n Received M a y 86, 1964
I n the preceding publications,’ we proposed the absolute configuration Ia for virosecurinine, Ib’ for allosecurinine (phyllochrysine), and Ia’ for securinine. (1) The paper which was published b y T. Nakano, T . H. Yang, S. Terao’ and L. ,J. Durham [Chem. I n d . (London), 1034 (1963)) represents part I11 of this series; for part I1 see T. Nakano, T. H. Yang, and S. Terao, J . O r g . Chem., 18,2619 (1963). (2) J. Parello, A. Melera. and R. Goutarel, Bull. m c . chim. France, 898 (1963). According t o a private communication from Dr. Parello, phyllochrysine was shown b y direct comparison to be identical with allosecurinine.
344 1
This assignment is not in agreement with that suggested recently by Tarello, et aLJ2on the basis of the relative rates of reaction of these alkaloids with methyl iodide, but the nuclear magnetic resonance evidence is more compatible with our proposed structure, as was already pointed out by us in a recent paper.3 Our conclusion was later supported by Horii, et al.,4who also proposed the absolute configuration Ia’ for securinine, an antipode of virosecurinine. 0
0
H Ia’
Ia 0
& 0
N ’
Ib
H Ib’
Parello, et a1.,2 examined the ultraviolet absorption spectra of allosecurinine and securinine and suggested that while securinine possesses the conformation b-1 (or a mirror image of b-1), allosecurinine exists in the conformation a-2 (or a mirror image of a-2). The same ultraviolet spectral observation was also made by Horii, et aLJ4who reported that the conformation of a mirror image of a-15 is preferred for securinine. Both these authors noted that the characteristic absorption a t 330 mp in the ultraviolet spectrum as well as the yellow coloring of securinine would originate most probably in transannular interaction from the nitrogen to the conjugated system in this alkaloid. However, in the conformation of a-2 (or a mirror image of a-2) assigned by Parello, et al., for allosecurinine, no interaction can arise between the electron pair of the nitrogen atom and the conjugated system because of an intervening methylene bridge, even if the ring A adopts a boat forme2 I n view of this contradictory conclusion made by Parello, et al., we have examined in some detail the ultraviolet absorption spectrum of allosecurinine, in comparison with that of virosecurinine, and the effects of solvents on their absorption spectra were studied. Allosecurinine and virosecurinine exhibited in ethanol solution two absorption maxima at 256 mp (log E 4.04),6 306 (3.11), 254.5 (4.21),6and 331 (3.26), respectively. The wave length and the maximum extinction coefficient of the lower wave length absorption bands in both these alkaloids are affected by a change of (3) T. Nakano, T. H. Yang, S. Terao, and L. J. Durham, Chem. I n d . (London), 1763 (1963). (4) Z . Horii, M . Ikeda, Y. Yamawaki, Y . Tamura, S. Saito, and K. Kodera, Tetrahedron, 19, 2101 (1963). ( 5 ) I n this case, according t o whether the electron pair of the nitrogen atom is either equatorial or axial in respect t o ring A, two conformers are possible. (6) As was already reported, this absorption band is due t o the a , & y , & unsaturated five-membered lactone moiety [see T. Nakano, T. H. Yang, and S. Terao, Telrahedron, 19, 609 (1963)).
