Two SYNTHESES OF POLYGALITOL
Aug., 1943
moles of oxidant consumed per mole of substance, against time in hours.
Summary 1. Rules relating to the oxidation of cyclic triols by lead tetraacetate have been stated in an expljcit form. 2. Standardized conditions for measuring the rates of oxidation of substances by lead tetra-
1477
acetate have been described. 3. The degree of resemblance of the oxidation curves of substances related in structure and configuration to the methyl-D-glucopyranosides has been determined. 4. Evidence has been presented concerning the configurations of styracitol and polygalitol. CAMBRIDGE, MASS.
RECEIVED MARCH17, 1943
THE DIVISION OF CHEMISTRY, NATIONAL INSTITUTE OF HEALTH, U. S. PUBLIC HEALTH SERVICE, AND FROM THE DEPARTMENT OF PHARMACOLOGY, UNIVERSITY OF MARYLAND SCHOOL O F MEDICINE]
[CONTRIBUTION FROM
Two Syntheses of Polygalitol (1,S-Anhydro-D-sorbitol) BY NELSONK. RICHTMYER, C. JELLEFF CARR AND C. S. HUDSON In a recent publication1 on polygalitol and its of styracitol for other p ~ r p o s e s . ~Polygalitol relation to styracitol, i t was stated that in view and styracitol, therefore, are epimeric, as Shinoda, of the codicting opinions and the lack of satis- Sato and Sato had claimed,s and accordingly factory evidence concerning the structure and polygalitol is to be represented as 1,5-anhydro-~coniiguration, especially of polygalitol, new sorbitol. Additional proof that polygalitol has the methods would be applied to the further examination of these substances. Thus the oxidation anhydro-D-sorbitol configuration is derived from of polygalitol and styracitol with periodic acid, the second synthesis in which D-glucose was followed by bromine water and strontium car- transformed to polygalitol by a series of reactions bonate, to strontium D-hydroxymethyldiglyco- which involved no change in the configuration late, proved that these anhydro hexitols possessed of the second, third, fourth or fifth carbon atoms the same 1,5-ring; the D-configuration of poly- at any time. Acetobromoglucose was converted disulfide,'j and this, in galitol followed from the known D-configuration to octaacetyl-/3,/3-diglucosyl When the turn, to tetraacetyl-/3-~-glucothiose.~ of styracitol. There are eight possible 1,5-anhydro-~-hexitols. latter -SH compound was shaken with Raney One of these, styracitol, has been synthesized nickel in absolute alcohol, according to the previously by Zervas,2by the addition of hydrogen general procedure of Bougault, Cattelain and to the l,%-ethylenic linkage of tetraacetylhy- Chabrier,* the sulfur atom was eliminated, and droxyglucal. The configuration of styracitol is tetraacetylpolygalitol could be obtained from the limited, therefore, to that of 1,5-anhydro-~- resulting solution. By the same procedure the mannitol or 1,5-anhydro-~-sorbitol. Definitive disulfide octaacetate underwent reductive cleavevidence has been presented by Zervas and Papa- age and desulfurization, and tetraacetylpolydimitriou3 that styracitol is 1,5-anhydro-~-manni- galitol was isolated in a 14% yield. tol. Experimental Part The mother liquors from synthetic styracitol Polygalitol from Tetraacetylhydroxyg1ucal.-The hydrowould be expected to contain the epimeric 1,5- genation of 745 g. of tetraacetylhydroxyglucalwas carried anhydro-D-hexitol. Polygalitol has now been (4) Bell, Carr, Evans and Krantz, J . Phys. Chcm., 4 2 , 507 (1938); isolated in a 4% yield from the mother liquors Dozois, Carr and Krantz, J. Bucf.,86,599 (1938); Carr and Forman, Bid. Chem., 128, 425 (1939); Krantz, Carr, Forman and Ellis, remaining from the preparation of a large amount JJ.. Pharmucol., 67, 187 (1939). ( 1 ) Richtmyer and Hudson, Txrs JOURNAL, 66, 64 (1943). (2) Zervas, Bcr., 68, 1689 (1930). (3) Zervas and Papadimitriou, ;bid., 78, 174 (1940). Although we
regard the evidence of Zervas and Papadimitriou as definitive, i t is true that their conclusionis in disagreement with that of Asahina and Takimoto [ibid., 64, 1803 (1931)],who studied the problem by an entirely different method of experimentation. In a forthcoming article, Hockett and Conley will disprove the experimental results of Asahina and Takimoto, and show conclusively that styracitol is 1,5-anhydro-~-mannitol(private communication).
(5) Shinoda, Sat0 and Sato, Bcr., 66, 1219 (1932). (6) Wrede, ;bid., 62,1756 (1919). (7) Wrede, 2. Phrsiol. Chcm., 119, 54 (1922). (8) Bougault, Cattelain and Chabrier, Compt. rend., 208, 657 (1939). We are indebted t o Mr. Theodore E. Perrine of this Institute for suggesting t o us the use of this method. The desulfurizing action of Raney nickel upon organic sulfides, particularly in the development of the structural formula of biotin, has been described by du Vigneaud, Melville, Folkers, Wolf, Mozingo, Keresztesy and Harris [ J . Bid. Chem., 146,475 (1942)l.
147h
kI.L'OS
E:
HICH'TMYER,
c. JRLLEFF C A R R AND c. s. HUDSON
$Jut, in small batches, according to the procedure of Zervas,2with a palladium catalyst. After deacetylation of the product there was obtained about IUS g. of crystalline styracitol, or 28:; of the theorclical yield. The combined mother liquors from ~ l i cs! yracitol crystallizations were kept in the laboratory for >is years. 9;the end of that time 15 g. of a ciiffererit substance had separated. This material Tras recrystallized from methyl alcohol as clusters of thin, more or lcss hexagonal plates which are typical of polygalitol. The niclting Iioint, 1411---141 ", and rotation, ! L Y 1% +-i2..1,' in wa:.i.r ( L . , S), icletiriricll it as polygalitol. 'i'he nieltiiig point was iiot tiepr ti \\.hen the substance \vas mixed with a n authentic sai t' of polygalitol, 111. 1,. i l l -112", from Polygali: .'erzegii. :I/>,!/.. CMcd, for CpH::L): C, 4.3 90; 1-1, 7.37 f>ou!itl: i', -kA,!J(I; FI, :jf; ! i is po+iblc hat the yrcltl of polygalitol can be increased !!y the selection of different conditions of temperature, .oivent arid catalyst fur t n t , Iiyc!rogeriaticjir of tcttaacetylhydroxyglucal. Preparation of Glucothiose Derivatives-Acetobromoglucose, prepared iii 3 1 1 8556 yield by the nqtliod of Helierich and Cuntheir." i v a b condensed lvith potassium r t h y l xanthate according to Schncider, CXle and Eisfeld,'O and the rcsulring tetraacetylglucosyl ethyl xanthate was isolated in a n 35':1 yield. Degradation of this substaiicc ii ; t h ,odium rriethylate to sodium glucothiosate;" !not tsolated), followed by usidst loti wit11 iodine and s u t m iluerit acetylation," protiuced a !KI: , yiihld of octaacetylj,p-diglucosyl disulfide,b of lii. 11. 1$2-1.K3ca and [ a ] % --1,jA" iii chloroforni I ! , 2 ) . The iatioii iii chloroform Iiai not lxen reportctl prwiousl 1f ila:ed lrith the valurs .aj"rr chloride and - 185' iii iLitrobenzerie.:' tlisulfide derivative 114' aluminum atiialgain was carrier1 $ ) u t according t o Schn er u i i l l i a t l ~ a l ~ the : amalgam appeared to bc lcss active, 40 that t \ w a n d one-half h o u r i action \vas required. 'L'iie yield \\-as 4.1 g. from 3 g. of the disulfide. The product, tetraacetyl-3-glucothiose, was rei,rystallized from cthcr i:.opentar;t in clusters of illin plates Tlit: 1i:rlting poiut i. i n agrcr\vhich nie1:ed at 74 7:).' : i i e t i t with that reporlcd origiriallv by M'redc'; t h e valiic ! 1:i .114", given b y Schneitlet arid i3ail.iz.11may be t h a t of a dimorphic motliticatioii i i i ! ) ( I 1 e t h y l alcohol 1 I . , 1 5 j , ti 2!13)t h e cornp';ulril Y l l L i l l - ~ l ' a i l ! ~ l l ,i i j ' l l --q.:.; , .
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Vol. 6.5
after five minutes, changing t o +47.0 (constant) after 12 weeks. Wrede reported [a]lSo- 13.57 -+ -6.78"in seven days; Schneider and Bansa reported [ C Y ] ~ O D --6,04'-* -37.0 after twenty-one days. Tetraacetylpolygalitol from Octaacetyl-p,p-diglucosyl Disulfide.--A mixture of 4 g. of the disulfide, 12 g. of Kaiiey nickel arid 200 cc. of absolute alcohol was shaken for teii days at room temperature. The nickel was removed by centrifugation, and the solution concentrated in P U C Z ~ io a sirup which was dissolved in ether and filtered from a small amount of flocculent precipitaLe. The ether was O the residual sirup \\-as extracted removed in U ~ C Z ~and by shaking i t several times with isopentam. As the isopentane evaporated it deposited clusters of acicular prisms recembling tetraacetylpolygalitol. The crystals were separated from adhering sirup and recrystallized from a mixture of ether arid isopeiitanr. The yield was 0.5 g. 'I'he product showed [a]*% + X Y O in chloroform (c, 2 ) . :rut1 a melting point of W . 7 4 "in agreement with tlie values rcported previously for tetraacetylpolygalitol.' X mi ii~eltingpoint showed nu depression. . l m d Calcd. for C141S1110y: C , 50.fi0; H, ti.07. Fourid. C . .31.71: H, i j , ! O . Tetraacetylpolygalitol from
[email protected] h e desulfurization of 1 g . of the tetraacetylglucothiose by 2.4 g. of Kaney nickel was carried out as above. Tetraacetylpolygalitol was isolated in sniall yield, and identified l)y melting point atid mixed melting point.
'1'h;mks are expressed to Ilr. -4rthur T. N e s s of this Laboratorv, for carryiiig out the iiiicrJmal>,-
Summary The configuration of polygalitol as 1,3-anhydrou-surbitol has been established coriclusively by two syntheses. I n the first synthesis, polygalitol was sliow~rito be the epimer of styracitol (1,;anliyclro-Ij-niari!iit~l~b y the isolation ol: both substatices iron1 tlie deacetylated products resulting from the hydrogenation of tetraacetylhycirusyglucal. I n the second synthesis, tetrnaceryIpolygalito1 was obtained simply by the tiesullurixation of tetraacetyl-~-D-glucothios~ \~:itli I< a m y nickel. 1; I::TIIESDA, MARYLAXD )
