FEBRUARY
196 1
[CONTRIBUTION FROM
537
AMINO SUGARS. XXIV THE
DEPARTMENT OF MEDICINE, HARVARD MEDICALSCHOOL,AND HOSPITAL]
THE
MASSACHUSETTS GENERAL
3-Amin0-3-deoxy-n-idose and 3-Amino-3-deoxy-~-gulose~ ROGER W. JEANLOZs
AND
DOROTHY A. JEANLOZ
Received June 10,1960 Methyl 3-acetamide3deoxy-a-~-idopyranoside, obtained by ammonolysis of methyl 2,3-anhydre4,6-O-benaylidene-aD-tdopyranoside, was transformed into 3-acetamido-l,6-anhydro-3-deoxy-j3-~-idopyranose, which waa identical with the product obtained in a side reaction of the ammonolysis of 1,6: 2,3-dianhydro-&~talopyranose.3-Aminc+3deoxy-~-gulose hydrochloride and 3-amino-1,6-anhydro-3-deoxy-~-~-gulose hydrochloride were obtained from methyl 3-acetamido-4,6-Obenzylidene-3-deoxy-n-Didop yranoside.
The recent isolation of 3-amino-3-deoxy-~- benzylidene-a-D-talopyranoside or of methyl 4,6glucose as a constituent of the antibiotic kana- O-benzylidene-2,3di-O-ptolylsulfonyl-a-~-galactomycin14 and of 3,6diamino-3,6dideoxy-~-glucosepyranoside. Removal of the benzylidene group of from the antibiotic neomycin,6 after the isolation I11 gave the crystalline methyl 3-acetamido-3af 3-amino-3-deoxy-~-ribosefrom puromycin16has deoxy-a-D-idopyranoside (I). A better yield of I brought interest to the 3-amino-3-deoxy- was obtained by purification through the crystalD-hexoses. Whereas all the 2-amino-2-deoxy-~- line 2,4,6-tri-O-acetyl derivative 11. It is possible hexoses have now been synthesized, only the that the conditions used to remove the benzylidene group, 60% acetic acid, may produce some acetyla3-amino-3-deoxy derivatives of ~-allose,~~8 Daltroselg D-glucose,'O and D-idose1'J2 are known. tioni4 of the primary hydroxyl group, resulting in I n the present publication the synthesis of a new the contamination of the final product, I, with its 3-amino-3-deoxy-~-hexose, 3-amino-3deoxy-~-gu- 60-acetyl derivative. Action of hydrochloric acid lose is described, as well as new derivatives of 3- on I resulted in the formation in high yield of the amino-3deoxy-~-idose. l,&anhydro derivative, which was characterized In the preceding publication,13 the synthesis of through the formation of its N-acetyl derivative methyl 3-acetamido-4,6-0-benzylidene-3deoxy-a- IX possessing a low solubility and excellent properD-idopyranoside (111) has been described, using ties of crystallization. Very little of the 3-amin0-3the ammonolysis of methyl 2,3-aihydro-4,6-0- deoxy-D-idose (as its N-acetyl derivative) could be detected in the mother liquors of IX by paper (1) Amino Sugars XXIV. This is publication No. 286 of chromatography. Thus, 3-amino-3deoxy-~-idose The Robert W. Lovett Memorial Unit for The Study of forms an anhydro derivative as easily as the 2Crippling Disease, Harvard Medical School at the Massa- amino-2-deoxy d e r i v a t i ~ e or ~ ~the ~ ' ~parent sugar, chusetts General Hospital, Boston 14, Mass. This investigation has been supported by a research grant from the D-idose.16 The same 3-acetamido-l16-anhydrc-3National Institute of Arthritis and Metabolic Diseases, deoxy-8-Pidopyranose (IX) was obtained by alkaNational Institutes of Health, Public Health Service (Grant line hydrolysis of 3-acetamido-2,Pdi-0-acetyl-] ,6 A-148 C5). This work was presented at the Fall meeting anhydro-3deoxy-p-~-idopyranose (X), a side prodof the Swiss Chemical Society, Lausanne, Switzerland, uct of the ammonolysis of' 1,6:2,3dianhydro-&uSeptember 1959.2 (2) R. W. Jeanloz and D. A. Jeanloz, Chimia, 13, 372 talopyranose (XI) ,12 The ease of formation, as (1950). well as the properties of crystallization of the 1,6(3) Special Investigator of the Arthritis and Rheumatism anhydro derivative IX, makes it an ideal compound Foundation. for the characterization of 3-amino-3deoxy-~(4) M. J. Cron, D. L. Evans, F. M. Palermiti, D. F. Whitehead, I. R. Hooper, P. Chu, and R. U. Lemieux, J . idose. The synthesis of 3-amino-3deoxy-~-gulose hyAm. Chem. SOC.,80, 4741 (1958). ( 5 ) K. L. Rinehart, Jr., and P. W. K. Woo, J . Am. Chem. drochloride XI1 was achieved using the method SOC.,80,6463 (1958). of inversion introduced by Baker, et a1.l' in the (6) C. W. Waller, P. W. Fryth, B. L. Hutchings, and J. carbohydrate field and already used in the syntheH. Williams, J. Am. Chem. Soc., 7 5 , 2025 (1953). sis of a 3-amino-3-deoxy-~-hexose derivative, (7) K. Freudenbere. -, 0. Burkhart. and E. Braun. Ber.. 59,714 (1926). methyl 3-acetamido-2,4,~tri~-acetyl-3~eoxy-~-~(8) R. U. Lemieux and P. Chu. J . Am. Chem. SOC.. , 80., allopyranoside.18 The crystalline 2-mesylate IV 4745 (1958). (9) E. Fischer, M. Bergmann, and H. Schotte, Ber., 53, 509 ( 1920). (10) S..Peat and L. F. Wiggins, J . Chem. SOC.,1810 (1938). (11) L. F. Wiggins, J. Cbem. SOC.,522 (1944). (12) S. P. James, F. Smith, M. Stacey, and L. F. Wiggins, J. Chem. SOC.,625 (1946). (13) R. W. Jeanloz, Z. T. Glazer, and D. A. Jeanloz, J . Org. Chem., 26, 532 (1961).
(14) See R. B. Duff, J . Chem. Soc., 4730 (1957). (15) R. Kuhn and W. Bister, Ann., 617, 92 (1958). (16) E. Sorkin and T. Reichstein, I;lelv. Chim. Acta, 28, 1( 1945). (17) B. R. Baker and R. E. Schaub, J . Am. Chem. Soc., 75, 3864 (1953); B. R. Baker, R. E. Schaub, J. P. Joseph, and J. H. Williams, J . Am. Chem. Soc., 76,4044 (1954). (18) B. R. Baker and R. E. Schaub, J . Org. Chem., 19, 646 (1954).
538
JEANLOZ AND JEANLOZ
VOL.
26
RO-C-H H-C-0
C,H,CH
I
I.R=H 11.R = CHsCO
H-C-0 CHZOR I
H-C-0 I
\O-CH2
CHzOR III.R=H IV. R = CH3S02
V.R=H VI. R = COCH,
/
I I C-H -C-H RO-C-H
I
H-C-NHCOCH~
I
RO-C-H
I
H-C-0-
I
IX.R=H X.R=CHsCO
-C-H
I
,C-H O\A-H I HO-C-H
H-C-OH H-C-R HO-C-H I H-C-0
I H-C-OI
I
-0-CHz
XI
VII. R = H VIII. R = COCH3
CH2OH
XI1.R NH, XII1.R =N-CHCmH'OH
-
I
I H-C-OH I
I H-C-OI -0-CH2
XIV. R = NHz.HCI XV. R = NHCOCH,
deoxy-D-gulose (XII).The second substance formed had a Raluoo-,ina of 1.28 to 1.33; it gave a purple 4,6-0-benzylidene-3deoxy-cr-~-gulopyranoside(V) spot with ninhydrin, reacted very slowly with with the best yield so far obtained in this type of the alkaline silver reagent, and not at all with transformation (97%). It is noteworthy that the aniline phthalate. The identity of this substance spatial configuration of t h e carbons at positions 2 has not been established. The fastest moving and 3 involved in the inversion axe in opposite con- compound had a of 1.57 (R, 0.45); formation (axial) to those of methyl Zacetamido- it did not react with aniline phthalate, and only slowly with the alkaline silver reagent; with 4,6-0-benzylidene-2-deoxy-3-0-methylsulfonyl-t~-~galactopyranoside, the only 4,6-0-benzylidene de- ninhydrin it gave a brown color. Judging from the rivative of a 2 or 3-aminodeoxy sbgar which has intensity of the ninhydrin reaction on samples resisted inversion under the standard conditions hydrolysed thirty minutes, two hours and six used.lQ Removal of the benzylidene group of V hours, it was inferred that formation of this third gave methyl 3-acetamido-3-deoxy-a-~-gulopyrano-compound waa favored by duration of hydrolysis. These various observations indicated this fast side (VII). As described above for the idoside derivative, a better ykld was obtained by puri- moving substance to be 3-amino-l,6-anhydro-3fication through the 2,4,6-tri-O-acetyI derivative deoxy-8-D-gulose. It has been isolated as a crystalVIII. The effect of secondary acetylation was, line hydrochloride (XIV), obtained in 58% yield however, less important. after a ten-hour hydrolysis of VII. The tendency to When the glycoside VI1 was hydrolyzed with 2N form a 1,6-anhydro ring seems, at least qualitahydrochlmic acid at 100°, three different compounds tively, to be much greater for the 3-amino-3were formed, as detected by paper chromatogra- deoxy derivative than for the 2-amino-2-deoxy phy (Fischer-Nebel solvent systemz0; Whatman derivativel21pZZand in the same order of magnitude No. 1 and No. 54 papers). The compound moving as for the parent sugar.2a The ease of formation of of 1.06, reacted the anhydro derivative XIV as well as its 3most slowly had a RCIluavrunind strongly with the aniline phthalate and alkaline acetamido derivative XV makes them ideal comsilver reagents, and gave a purple color with nin- pounds for the identification of 3-amino-3-deoxyhydrin. This compound was formed when hy- D-gulose. Characterization of 3-amino-3-deoxydrolysis was carried out for thirty minutes; but D-gulose (XII) waa obtained by reaction of 2when hydrolysis lasted two or six hours, it could hydr~xynaphthaldehyde~'with the product of be detected in small quantities only. On the basis (21) R. W.Jeanloz, J . Am. Chem. SOC.,81, 1956 (1959). of its properties, it was assumed to be 3-amino-3(22) E. E.van Tamelen, J. R. Dyer, H. E. Carter, J. V. (19) Z. Tarasiejska and R. W. Jeanlos, J . Am. Chem. Pierce, and E. E. Daniels, J . Am. Chem. SOC.,78, 4817 reacted very easily with sodium acetate in Methyl Cellosolve solution to give methyl 3-acetamido-
SOC.,79,4215 (1957).
( 1956).
(20) F. G. Fischer and H. J. Nebel, 2. Physiol. Chem., 302,lO (1955).
Soc., 77,1021 (1955).
(23) L. C. Stewart and N. K. Richtmyer, J . Am. Chem.
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1961
539
acetyl-1,6-anhydro-3deoxy-&~idopyranose (X)" in 2.5 ml. of 0.2N sodium methoxide was refluxed for a few minutes. After removal of the cations and purification aa d e scribed above, the crystdine residue was recrystalhed from methanol to g v e 128 mg. (99%) of elongated priam, map. 245-246', [=ID -96 f 1"(in methanol, c 1.54). Anal. Calcd. for CaHllOa: C, 47.29; H, 6.45. Found: EXPERIMENTAL C, 47.30; H, 6.59. b ) From I. A solution of 60 mg. of 1 in 0.5 ml of 2N Melting points were taken on a hot stage, equipped with hydyhloric acid was heated in
