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COhI1ZIUNICATIONS TO
THE
EDITOR
VOl. 84
T H E ISOLATION AND SYNTHESIS OF T H E METHYL ESTER-METHYL a-GLYCOSIDE OF
react with an excess of (methyl tri-0-acetyl-a-Dglucopyranosyluronate) bromide and mercuric cya~-O-@-D-GLUCURONOSYL-N-ACETYL-Dnide in a mixture of nitromethane and benzene GLUCOSAMINE (HYALOBIURONIC ACID)’ for 8 days. The resulting product was purified by Sir: chromatography on silicic acid, heated for 15 Polysaccharide components of animal connective min. with 60yGacetic acid, and acetylated with tissue, such as hyaluronic acid, chondroitin sul- acetic anhydride in pyridine solution, to give I1 fate and dermatan sulfate, are built of alternate in 427; over-all yield, m.p. 2;37 - 2 3 S o , [ c Y ] ~ ’ D+30° units of uronic acid and hexosamine linked a t posi- (c O.W, CHCl:{),identical with the product detions 4 and 3, respectively. Isolation of a 3 - 0 - scribed above. .InaZ. Calcd. for C26H&iN: C, 0-D-glucuronosyl-hexosamine disaccharide, chon- 49.13; H, 5.Si; OCH3, 9.7i. Found: C, 49.27; drosin, from chondroitin sulfate was reported H , 5.96: OCH3, 9.91. Reduction of I1 with lithalready in 1914,2 whereas a similar disaccharide, ium borohydride in tetrahydrofuran, followed by 3 - 0 - ( p - D - glucopyranosyluronic acid) - 2 - amino- acetylation, gave a product identical with VI, 8-deoxy-D-glucose (hyalobiuronic acid) (I) re- described below. cently has been isolated from hyaluronic acid. The product resulting from the reaction of V with We wish to report the first synthesis of this type equimolecular quantities of tetra-0-acetyl-a-Dof disaccharide, isolated as the fully acetylated glucopyranosyl bromide and mercuric cyanide in methyl ester-methyl-a-glycoside of I , namely, benzene-nitromethane a t 30’ for 3 days was demethyl 3-O-(methyl tri-0-acetyl-P-D-glucopyrano- acetylated catalytically with sodium methoxide, syluronate) -2 - acetamido -4,B-di-0- acetyl - 2 - deoxy- and heated with 6n7c acetic acid. After purifia-D-glucopyranoside (11). The same compound cation through a charcoal-Celite (1 : 1) column, I1 was obtained directly by degradative meth- methyl 3-0-(p-D-glucopyranosyl)-2-acetamido-2-deanolysis of hyaluronic acid, then by acetylation, oxy-a-D-ghcopyranoside (VI) was obtained in and from hyalobiuronic acid (I), by glycoside 35% yield, m.p. 252-254’; [(Y]~’D +44’ (c I.[)[), formation and acetylation. H20). &lnal. Calcd. for C15HeTOllN: C, 45.33; Dried hyaluronic acid (1.10 g.) from human H , 6.85. Found: C, 45.88; H , 7.13. Acetylation umbilical cord,j was refluxed with 6Yc methanolic of VI with acetic anhydride in pyridine solution hydrochloric acid for 24 hr. The resulting sirup, gave the hexa-0-acetyl derivative in 75% yield, treated with pyridine and acetic anhydride gave, m.p. 236-237’, [ C Y ] ? ~ D +21’ (c 1.11, CHC13). after purification by chromatography on silicic -1nal. Calcd. for C2iH39OliN: C, 49.92; H, 6.05. acid, 0.76 g. of crystalline material. Recrystalli- Found: C, 50.02; H , 6.08. zation afforded 0.22 g. of 11, m.p. 236-238’, [ a ] ” D Acknowledgement.-This work was supported 4-30’ (c 0.68, CHC13). *~lnal.Calcd. for C26H3701,X: C, 49.13; H, 5.87: N , 2.20; OCH3, 9.77. by research grants from the National Institute of Found: C, 49.19; H, 5.95; N, 2.33; OCHJ, Arthritis and Metabolic Diseases, Kational In10.36. Hydrolysis of I1 with barium methylate stitutes of Health, U. s. Public Health Service in methanol a t 0’ gave methyl 3-o-(p-D-glUCO- (Grant -1-3564) and from the National Science pyranosyluronic acid) -2 - acetamido - 2 - deoxy - a - D- Foundation (Grant 9-2312). The authors are glucopyranoside (111) in 95% yield, m.p. 207- very grateful to Dr. K. Meyer for the gift of N 210°, [ a ] =+31° (c 0.74, CH30H). Anal. Calcd. acetylhyalobiuronic acid. for C15H15012r\j’HzO: C, 41.96; H, 6.34. Found: (8) On leave of absence f r o m t h e Weizmann I n s t i t u t e o f Sciences C, 41.94, H, 6.40. Esterification of I11 with Rehovoth, Israel. diazomethane or methanolic hydrochloric acid DEPARTMENT OF BIOLOGICAL CHEMISTRY ASD MEDICISE afforded IV, identical with the compound de- HARVARD MEDICAL SCHOOL AND W. JEANLOZ GENERAL HOSPITAL ROGER scribed below. 3 - 0 - (,R - D - glucopyranosyluronic MASSACHUSETTS HAROLD M. FLOWER@ acid)-2-acetamido-2-deoxy-~-glucose,~ obtained by BOSTOX14, MASS. RECEIVED MAY19, 1962 N-acetylation of I , was refluxed with 1.5 N methanolic hydrochloric acid and gave, after purification by chromatography on silicic acid, methyl 3 - 0 - (methyl ,R - D - glucopyranosy1uronate)O F “SULFENE” T O KETENE 2 - acetamido - 8 - deoxy - a - D - glucopyranoside T H E CYCLOADDITION DIETHYLACETAL (IV) in 50% yield, m.p. 223-225’, [ a ] ” D +16’ (c 1.09, CH30H). Acetylation of 1lr gave I1 in Sir : yield. Sulfenes as reactive intermediates have been Methyl 2 - acetamido - 4,6 - 0 - benzylidene - 2- proposed by various workers. Diphenylsulfene deoxy - (Y - D - gl~copyranoside~ (17) was allowed to was suggested as an intermediate in the reaction of diphenyldiazomethane with sulfur dioxide which (1) Amino Sugars X X X I I , a n d publication h-o, 313 of t h e R o b e r t W. Lovett Memorial Group f o r t h e S t u d y of Crippling Disease, decomposed to form tetraphenylethylene. LikeHarvard Medical School a t t h e Massachusetts General Hospital, wise a similar structure was postulated by KloosterBoston 14. ziel and Backer.2 “Methylenesulfene” (CH2= (2) J. Hebting, Biochem. Z . , 63, 353 (1914). SOz) was proposed by Hesse and Reichold3as formed (3) T. Isikawa, TGhoku J . E x p l l . M e d . , 63, 217 (1951). (4) M. M . R a p p o r t , B. Weissmann, A . Linker a n d K . Meyer, by the interaction of diazomethane with sulfur g4
N a f u v e , 168, 996 (19,51). ( 5 ) R . W. Jeanloz a n d E . Forchielli, J . B i d Chem., 186, 495 (1950). ( 6 ) B. Weissmann and K. Meyer, J . A m . Chem. Soc., 76, 17.53 (1954). (7) A. Seuberger, J . Chem. Soc , 20 (1901); I>. F. Wiggins, ibid., 18 (1947).
(1) H. Staudinger a n d F. Pfenninger, Ber., 49, 1941 (1916). (2) H . Kloosterziel a n d H . J. Backer, Rec. trau. chim., 71, 1235 (1952). (3) G. Hesse a n d E. Reichold, Bey., 90, 2106 (1957).
Aug. 5, 1962
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BOOKREVIEWS
bands indicative of unsaturation or a carbonyl function. The n.m.r. spectrum (in carbon tetrachloride) is in full agreement with the structure of I. The peak for the six methyl hydrogens was centered a t 8.76 (relative to tetramethylsilane) and the peak for the four methylene hydrogens of the ethoxy groups was centered a t 6.55 r. A single unsplit peak occurring a t 5.93 r was attributed to the four methylene hydrogens of the ring. The relative areas were 3:2:2. No vinyl protons were detected. To date, attempts to isolate like products from methanesulfonyl chloride and the following unsaturated systems have been unsuccessful : ethyl vinyl CH,=C( OCH?CH3)2 + CHaS02Cl + (CH3CH2)aN + ether, p-tolylmercaptoethene, ethoxyacetylene, diCHz-C( OCH?CH$)? phenylketene, ketene-diethylmercaptal, vinylidene I ‘ chloride and cyclopentadiene. It appears from S02-CHY + (CH3CH2)aS.HCl these results that a facile polarization of the type 1
dioxide. Recently, Stork and Borowitz4 and, independently, Opitz and Adolph5 have formed four-membered-ring sulfones by interaction of enamines and methanesulfonyl chloride in the presence of base, presumably through a sulfene intermediate. Methanesulfonyl chloride has now been found to react with ketene diethylacetal in the presence of triethylamine to give the cycloaddition product 3,3-diethoxy thiacyclobutane- 1,l-dioxide (I). The structure of I was confirmed by elemental analysis, molecular weight, infrared and nuclear magnetic resonance spectrometry.
A solution of methanesulfonyl chloride in ether was added dropwise to a solution of ketene diethylacetal and triethylamine in ether. An immediate precipitate of triethylamine hydrochloride formed. The amine hydrochloride was removed by filtration (96Oj, yield) and the ether solution was evaporated under reduced pressure to give I in %yoyield, dnal. Calcd. for C7HI4O4S: C, m.p. 49-50’. 43.30; H, 7.22; S, 16.49; mol. wt., 194. Found: C,43.59; H, 7.10; S,16.74; mol. wt., 202. The infrared spectrum of I shows the presence of the sulfone grouping a t 7.45 and 8.65 p and the presence of ether linkages a t 9.15-9.25 1. There were no (4) G. Stork a n d I. J. Borowitz, J . A m . Chem. Soc., 84, 313 (1962). ( 5 ) G. Opitz a n d H. Adolph, Afrgew. Chem., 74, 77 ( 1 9 6 2 ) . (6) ADDEDIN PROOF.-The same product has been isolated b y Stork a n d co-workers (private communication).
()C=C(”
++)E-c
