Synthesis of acylated thioureylenedisaccharides

摘要

495J. CHEM. SOC. PERKIN TRANS. 1 1990 Synthesis of Acylated Thioureylenedisaccharides Martin Avalos," Reyes Babiano, Pedro Cintas, Jose L. Jimbnez, and Juan C. Palacios Department of Organic Chemistry, University of Extremadura, 0607 1-Badajoz, SpainJose Fuentes Department of Organic Chemistry, University of Seville, 4 107 I-Seville, Spain Thioureylenedisaccharides have been prepared from sugar isothiocyanates and aminosugars. Thus, a thiourea bridge connects the (C-I )-(C-2) or (C-2)-(C-2) positions of some pentose, hexose, and heptose frameworks with different anomeric patterns in compounds (16)-(28). With this aim, several C-2-functionalised derivatives of compound (7) have been synthesized. A (Z,Z)-conformation is proposed for thioureylenedisaccharidesin solution.Many biologically important products have two sugar units joined through an atom (as oxygen in disaccharides) or group of atoms (as phosphate in dinucleotides and agrocinopines I). The AcOreplacement of these classical bridges gives rise to compounds of great structural analogy with natural products, and which may be used as enzyme inhibitors. For this reason, much effort has CI-been directed toward the synthesis of such compounds. Thus, iiS-,2 N-,3 and C-disaccharides are already known. Pseudodi- S saccharides with disulphide and hydrazine bridges, and (3)R' = OAC, R2= Hpseudodinucleotides with ~arbonate,~methylphosphonate,8 (1)R' =OAC, R~=H arba am ate,^ thiocarbamate," thiophosphate," phosphor-(2) R' = H, R2= OAC (4) R' = H.R2 = OAC amidate," and diphenylsilanel3 bridges have been also synthesized. Sugars joined by urea or thiourea groups, non- ionic isosteric bridges 01phosphates, have been studied to some extent. These bridges are present in a few natural products such as gl yc~cinnamoylspermidines,'~a family of broad-spectrum antibiotics. The condensation of monosaccharides with urea,' the benzoylation of glycosylureas,16 the addition of water l7 and hydrogen sulphide '* to diglycosylcarbodi-imides,and the reaction of glycosyl isothiocyanates with glycosylamines produced 1,3-diglycosylureas and 1,3-diglycosylthioureas,res-pectively. The same compounds were also obtained as side- products in several reactions of glycosyl isocyanates 2o and glycosyl isothiocyanates.2 On the other hand, two 2-deoxy-2- glycosylureidosugars have been and Jochims and Seeliger23 have described the only urea and thiourea derivatives in which both nitrogen atoms are joined to non- anomeric carbon atoms. In this paper we report on the preparation of a wide set Iof thioureas in which the HN-CS-NH group links the aldopyranose frameworks that have different anomeric patterns, through the reaction of the free amino group of one aminosugar with a sugar isothiocyanate.(10) (9)Results and Discussion Synthesis of Precursors.-Starting compounds (1),24 (2),2 Scbeme 1. Reagents: i, EtOCH=C(COOEt),; ii, Ac,O-pyridine; iii, (3),26(4),23 (5)," and (6)27have been prepared by methods Br,-CHCl,-water described in the literature.The synthesis of several 0-acyl derivatives of 2-amino-2-deoxy-~-gZycero-~-~-gZuco-heptopy-The p-anomer (13) 1was easily available (total yield 47) ranose hydrochloride28 (7)t and their use as intermediates for through the N-protection of compound (7) with 4-methoxy- the synthesis of sugar thioureas is now described. The reaction of compound (7) with diethyl ethoxymethylenemalonate gave compound (8).Conventional acetylation of (8) afforded penta- t Correct name: 2-amino-2-deoxy-~-~-glycero-~-gluco-heptopyranose. $ Note: the text uses 01, p to describe the stereochemistry of the anomeric acetate (9) which led to the amine (10) through N-deprotection centre with respect to that at C-5, for comparative purposeswith bromine in humidified chloroform.This alternative homomorphous sugars. The strictly correct (IUPAC) nomenclature for synthesis follows with greater total yield (82) that was the heptopyranoses should show the reverse anomeric configurational previously reported 29 (Scheme 1). prefix (see Experimental section). 496 J. CHEM. SOC. PERKIN TRANS. I 1990 (7)Ii AC H2 Ac N-C OAc . C lii AcOCH~ H (12)Iiii OAc CI-(13) Sebeme 2. Reugents: i, 4-MeOC6H,CHO-1M-NaOH ii, Ac@-pyridine; iii, SM-HC1-acetone AcOCH,H amp;R2 AcO NdkS Acb OAc (14) R'= OAC, R2 =H (15) R' =H. R~=OAC benzaldehyde (Scheme 2). The Schiff derivative (11) was then acetylated to give penta-acetate (12),which showed a high value of J1,2(8.3 Hz), in accord with a @-configuration. A similar anomeric anchorage has been observed in the D-glucosamine series.25 Isothiocyanates (14)30and (15)were prepared from amines (10)and (13)with thiophosgene in a two-phase reaction system.Synthesis of Thioureylenedisaccharidesand Analogues.-Ano-meric and C-2 carbons of different sugars have been linked by a thiourea group in the reaction of 2,3,4,6-tetra-O-acetyl-P-o-glucopyranosylamine(5) with 1,3,4,6-tetra-U-acetyl-2-deoxy-2-isothiocyanato-a- and -P-~-glucopyranose,~~~~~(3) and (4) respectively, to give products (16) and (17). From the heptopyranose (14)the thiourea (18)was obtained. In the same way, 2,3,4-tri-0-benzoyl-P-~-ribopyranosylisothiocyanate (6)was linked to the sugar residues of 2-deoxy-/3-~-glucopyranose and 2-deoxy-~-glycero-P-~-gZuco-heptopyranosein the thio- ureas (19)and (20)by reaction with the amines (2)and (13), respectively.On the other hand, in compounds (21)-(28) the thiourea bridge connects the C-2 atoms of hexose-hexose, heptose-heptose, and hexose-heptose frameworks with different anomeric patterns. All these reactions were performed with equimolar amounts of aminosugar and isothiocyanate in pyridine at room (20) temperature. Structures of new compounds were demonstrated by elemental analyses and spectral cata. The U.V. spectra showed Amx. at 243-249 nm, as W? :Id be expected, for the thiourea moiety, and the i.r. spectra showed characteristic absorption bands of NH at 3 390-3 300 and -1 540 cm-'.'H and 13C n.m.r. spectra of products (16)--(28) show some analogies with those other thioureas already des~ribed,'~~~~~~~*~'althoqh the presence of two sugar rings made their interpretation difficult. Molecular symmetry of compounds (21)and (22)simplified their spectra and thus they served as model compounds. Resonances of compound (23) were coincideutal with those of (21)and (22),as might have been expected. The thioureas (24)--(26) showed analogous n.m.r. spectra to their homomorphs (21)--(23),except for the presence of the 6-H proton and C-6 carbon signals. The 'H n.m.r. spectra of the sugar moieties of unsymmetrical thioureas (16)-(18),(27),and (28)are almost superposable on those of symmetrical thioureas (21), (22), (24), (25),and (29)19when they have the same sugar framework. The ribopyranosyl residue of compounds (19) and (20) showed n.m.r.spectra analogous to that of the tri-0-benzoylribopyranosylamine27 except for 1-H. This proton appears shifted downfield (-1.5-2.0 p.p.m.) in a similar way as for other thioureas with respect to its parent aminosugar.'9.27*30*31 All compounds described showed a 4C,(~)conformation for hexose residues or a 'C4(~) conformation for heptose residues. The 4C1(~)conformation of the ribopyranosyl residues contrast with that 'C4(D) of the parent isothiocyanate (6)." The f3-anomeric configuration has been assigned on the basis of the large Jl,2value (8.2-10.0 Hz), and the a-anomeric configurations are consistent with a small J1,2value (3.24.0 Hz) (see Table 2).J. CHEM. SOC. PERKIN TRANS. 1 1990 Ac OCH, /s=c H:+amp;kbsol; (21) R1=F?=OAc, R2=R4= H (22) R' =R3= H, R2=R4= OAC (23) R'=R~=OAC,R2=R3=H OAc (27) R' =R3 = OAC. R2=R4=H (28) R' =R3 =H, R2=R4=OAc Generally, 1,3-disubstituted alkylthioureas exist in solution as an equilibrium mixture of three conformational isomers: (2,2),(Z,E),and (E,Z).The free-energy barrier to the internal rotation for thioureas 32-37 is -50 kJ mol-'. The (E,E)-isomer has not been dete~ted.~' The chemical shifts of 1-H or 2-H protons joined to the thiourea bridge are similar to those of the corresponding protons of the 2-isomer in sugar thioforma- mide~,~~and coincide with the chemical shifts of sugar protons 497 H S H H H S H H H Z E Figure. joined to the unsubstituted nitrogen of N,N'-bis(glycosyl)-N-(2-thia~olin-2-yl)thioureas?~In these latter compounds the (Z,Z)-conformations are fixed by an internal hydrogen bond.On the other hand, the large couplings J1,NHor J2,NH observed agree with an antiperiplanar disposition between these protons. For these reasons, we propose a (2,Z)-assignment to the major isomer of compounds (16)--(18) in CDC13 solution at room temperature (see Figure). This assumption was confirmed by means of low-temperature n.m.r. experiments for compound (21). The 'H and I3C n.m.r. spectra at 193 K and 298 K are closely similar (see Tables 1 and 3), showing the presence of only a single conformer at both temperatures.Experimental General Methotis.-M.p.s were determined using a Gallen- kamp apparatus, and are uncorrected. Optical rotations were measured with a Perkin-Elmer 141 polarimeter. T.1.c. was performed on silica gel GF254 (Merck) with detection by U.V. light or iodine vapour. 1.r. spectra (KBr discs) were recorded with a Perkin-Elmer 399 spectrometer, and U.V. spectra (ethanol solutions) with a Pye-Unicam SP8-250 or a Beckman 50 instrument. 'H n.m.r. spectra were obtained with Perkin-Elmer R-32 (90 MHz), Bruker AC 200-E, and Varian XL-200 (200 MHz) instruments. 13C N.m.r. spectra were recorded on a Bruker AC 200-E or a Varian XL-200 (50.2 MHz) spectrometer. For n.m.r. experiments at low temperature, the spectrometer was fitted with a variable-temperature accessory capable of maintaining temperature to within amp;l K, and spectra were recorded in 2H,acetone solution at 298, 273, 243, 213, and 193 K.Elementary analyses were performed using a Perkin- Elmer 24OC analyser. 2-Deoxy-2-(2,2-bis(ethoxycarbonyl)uinylamino)-P-~-gly-cero-L-gluco-heptopyranose(8).-To a suspension of compound (7) (29.5 g, 120.2 mmol) in methanol (600 ml) were added triethylamine (42 ml) and diethyl ethoxymethylenemalonate (26.0 ml, 130.0 mmol) and the mixture was refluxed for 5 min. Crystals obtained by cooling (31.0 g) were washed with 1: 1 ethanol-ether and then with ether. Concentration of mother liquors, followed by refrigeration, afforded two additional crops (total yield 41.3 g, 91).Recrystallisation from methanol gave the title compound as needles, m.p. 193-195 OC (decomp.);a,$7 -139O, -147O, -170.5", -318", and 01:amp; -581O (c 1.0, pyridine); A,,,. 277 nm (E 21 900); vmax. 3 380-3 100 (OH and NH), 1 680,1650 (GO),1 605 and 790 cm-' (GC)(Found: C, 47.1; H, 7.0; N, 3.9. C15H25N010 requires C, 47.49; H, 6.64; N, 3.69). 1,3,4,6,7-Penta-O-acetyZ-2-amp;oxy-Z{ 2,2-bis(ethoxy-carbonyl)uinylamino)-P-~-glycero-~-gluco-heplo~vranose 498 J. CHEM. SOC. PERKIN TRANS. I 1990 Table 1. 'H N.m.r. chemical shifts of compounds (16)-(28)" Compound Ring 1-H 2-H 3-H 4-H 5-H 5-H' 6-H 6-H' 7-H 7-H' NH A 6.28d 5.07m 5.3-5.2m 4.03m 4.29dd 4.08dd 6.64d B 5.69m 4.95t 5.33 5.07t 3.85m 4.36dd 4.07dd 6.92d A 5.8Od 5.25-5.2m 3.85m 4.29dd 4.1 3dd 6.87d B 5.74t 4.98t 5.33 5.05t 3.85m 4.37dd 4.07dd 6.89d A 6.-5.1-5.Om 5.3-5.1m 4.04dd 5.3-5.1 m 4.25dd 4.15dd 6.86d B 5.69m 4.90t 5.33 5.03t 3.9 1m 4.32dd 4.24.b 7.08d A 5.74d 5.2-5.1 m 3.78m 4.26dd 4.12dd 6.85d B 6.38d 5.44dd 6.22t 5.47m 4.34.1m 7.25d A 5.63d 4.97m 5.3-5.1m 4.06m 5.3-5.1m 4.4-4.om 6.80d B 6.38m 5.6-5.4m 6.31t 5.6-5.4m 4.4-4.om 7.29d A=B 6.28d 5.05m 5.3-5.1m 4.m 4.26dd 4.07dd 6.50d A=B 6.28d 5.02m 5.29t 5.16t 4.15m 4.24dd 4.03dd 7.14d A=B 6.17d 4.91m 5.23 5.18t 4.25m 4.25dd 3.84dd 7.65d A=B 5.81d 5.24.9m 5.41 t 5.2-4.9m 3.92m 4.34.1m 6.3 A 6.34 5.24.9m 5.3-5.2m 4.05m 4.29dd 4.07dd 6.48m B 5.76d 5.24.9m 5.3-5.2m 5.12m 3.88m 43-41 m 4.14.0111 A=B 6.27d 5.1-5.Om 5.3-5.1m 4.06dd 5.3-5.1m 4.26dd 4.13dd 6.14d A=B 5.77d 5.2-5.b 5.32t 5.08t 3.97dd 5.23m 4.33dd 4.19dd 6.54d A 6.34m 5.3-5.b 4.08dd 5.3-5.om 4.27dd 4.12dd 6.25d B 5.67d 5.3-5.h 3.88dd 5.3-5.b 4.35dd 4.14dd 6.34m A 6.27d 5.2-5.Om 5.3-5.2m 4.07dd 5.3-5.2m 4.24dd 4.13dd 6.42d B 6.27d 5.2-5.Om 5.3-5.2m 4.02m 4.27dd 4.08dd 6.43d A 5.77d 5.2-5.0111 5.33t 5.06t 3.88dd 5.3-5.1m 4.31dd 6.56d B 5.81d 5.2-5.0111 5.38t 5.14t 3.95m 4.3-4.1m 6.53d a In CDCI,.Rings A and B are the sugar moiety joined to N and N atoms respectively. ' In C2H6acetone at 298 K. In C2H6acetone at 193 K. Table 2. 'H N.m.r. coupling constants of compounds (16)--(19) and (21)-(28)" Ring J1.Z J2,3 J3.4 J4.5 J5.6 J5.6' J6.6' J6,1 J6,1' Ji.7' J1.m J2,~n A 4.0 4.2 4.8 13.2 8.8 B 8.8 8.8 8.8 9.8 4.8 4.4 12.6 8.8 A 9.0 4.0 3.0 13.0 10.0 B 10.0 9.5 10.0 9.5 4.5 3.0 13.0 9.0 A 8.0 2.2 5.1 6.9 12.3 8.6 B 9.4 9.4 9.7 4.7 13.1 8.3 A 9.2 8.0 4.7 2.2 12.5 10.0 B 9.4 2.8 2.8 10.0 A=B 3.6 9.5 9.5 4.0 2.0 14.0 8.8 A=B 8.2 10.0 10.0 9.2 A 4.0 4.0 2.0 13.0 B 8.2 A=B 3.2 8.8 8.8 9.1 2.9 5.1 6.5 12.4 8.8 A=B 8.6 9.6 9.6 9.6 1.7 3.8 7.4 11.9 9.4 A 8.0 3.2 5.1 7.7 12.1 8.4 B 8.3 9.4 1.7 4.5 7.7 11.7 A 3.6 9.0 2.6 5.8 7.3 11.4 8.5 B 3.6 4.2 2.2 13.4 8.5 A 8.6 9.6 9.6 9.6 1.7 3.9 7.4 11.8 9.3 B 8.4 9.8 9.8 9.8 9.3 " In CDCI,.(9).--Conventional treatment of compound (8) (40.0 g, 105.0 NH) (Found: C, 51.3; H, 6.2; N, 2.3.C25H35N015 requires C, mmol) with pyridine (300 ml) and acetic anhydride (240 ml) 50.93; H, 5.98; N, 2.37). overnight at room temperature gave the title compound (9)(59.1 1,3,4,6,7-penfa-0-acefyl-2-amino-2-deoxy-P-D-glymr0-L-g, 95). RecrYstallised from aqm it showed m.Pm gluco-heptopyranose Hydrobromide (10).-To a solution of 122 OC; Calk2 -83.50, CaI:+S -880, Ca1226 -lolo, CaIz36 amp;ester (9) (24.8 g, 42.1 mmol) in chloroform (60 ml) was added -1890yand a325 -3470 (' '.09 'max-275 nm gradually a solution ofbromine (7.0 g, 43.8 mmol) in chloroform (22 300); 'max. 280-3 loo(NH)7 740, 6709 630 (c--o)y (150 ml) containing water (0.75 ml). Crystallisation of free 6oo and 795 cm-l (-1; 'euro;I(CDC13) 1.25 (3 H,T, Me), lS3O (3 amine (10) began at room temperature and was completed by s9Hyt*Me)92.00 (9 H9 OAc), 2'08 (3 H9s9OAc)*2m25(3 H9 dilution with ether (19.9 g, 95).Compound (10) decomposesOAc), 3*80(l H, m, 5-H),4.15 (2 H, 9, CH2), 4.22 (2 H, 9, CH2), above 185OC without melting (lit.,29 lg(t-182 OC).4.00-4.40 (4 H, m, 2-H, 6-H, and 7-H2),5.10 (1 H, t, J9.3 Hz, 4-H), 5.36 (1 H, t, J9.3 Hz, 3-H), 6.26 (1 H, d, J4.0 Hz, 1-H), 7.92 2-Deoxy-2-(4-methoxybenzyle)~m~no-a-~-glycero-(ll).-To a solution of compound (7)(1 H, d, J 13.3 Hz, CH=C), and 9.05 (1 H, dd, J 9.7, 13.3 Hz, L-gluco-~epfopy~uno~e J. CHEM. SOC. PERKIN TRANS. 1 1990 Table3. * 3C N.m.r. chemical shifts of compounds (16)--(28)'" Ring c-1 c-2 c-3 c-4 c-5 C-6 c-7 c=s A 90.28 55.68 70.62 67.26 69.54 61.52 183.92 B 82.61 71.00 73.62 68.22 72.62 61.77 A 92.23 57.15 72.96 68.08 72.64 61.57 184.67 B 82.5 1 70.51 73.25 67.63 72.64 61.48 A 89.60 55.61 70.64 66.38 69.87 66.38 62.00 184.15 B 82.35 70.33 73.14 67.99 72.45 61.64 A 94.0 1 57.36 72.8 1 67.49 72.40 61.60 185.12 B 80.54 69.24 69.15 67.09 62.97 A 92.80 57.24 73.03 67.30 73.03 66.47 62.33 185.59 B 80.88 69.69 69.56 66.47 63.04 A=B 90.46 55.92 70.96 67.42 69.72 61.68 183.55 A=B 90.78 56.52 7 1.06 68.70 70.57 62.33 185.20 A=B 90.46 55.65 70.79 67.00 69.60 6 1.48 184.29 A=B 92.9 1 57.33 72.45 68.55 72.13 61.53 183.97 A 89.85 57.32 70.4 1 67.23 69.60 61.57 183.78 B 92.74 57.54 72.70 67.61 72.61 61.38 A=B 90.28 55.65 71.03 66.53 69.87 66.3 7 62.1 3 183.53 A=B 93.27 57.52 73.02 67.28 73.02 66.58 62.85 184.30 A 89.78 55.22 72.75 66.29 69.75 65.65 62.06 183.73 B 92.83 57.17 72.93 66.29 70.43 65.65 62.09 A 90.13 55.48 70.70 66.32 69.35 66.32 61.36 183.78 B 90.25 55.48 70.85 67.15 69.49 61.88 A 93.02 57.45 73.09 67.14 72.38 66.48 61.70 184.27 B 93.02 57.63 73.30 68.57 72.84 62.72 'Assignments of C-3, C-4, and C-5 resonances may be interchanged. In CDCl,.'In 'H,acetone at 298 K. In ZH,acetone at 193 K. (31.5 g, 128.0 mmol) in lw-sodium hydroxide (150 ml) was added 4-methoxybenzaldehyde (23.0 ml, 189.0 mmol).The mixture was stirred vigorously at room temperature; a white solid crystallised out, and was separated and washed successively with cold water, ethanol, and ether to give compound (11) (26.2 g, 62), m.p. 190-192OC; ai8 -46", b:?g -48.5", a:amp; -55", ai!6 -105.5", a$amp; -103' (starting value), a;' -55", a1578 -57.5", a:amp; -66S0, aamp;, -129.5", and a:amp; + 724.5" (final value, 6 days) (c 1.0, pyndine); vmax.3 460-3 160 (OH), 1 635 (GN), 1 600, 1 510, and 830 cm-' (aromatic) (Found: C, 54.4; H, 6.5; N, 4.2. C15H21N07requires C, 55.04, H, 6.47; N, 4.28). 1,3,4,6,7-Penta-O-acetyl-2-amp;oxy-2-(4-methoxybenzyl-idene)amino-a-D-glycero-L-gluco-heptopyranose(12).--Conven-tional treatment of compound (11) (25.8 g, 78.9 mmol) with pyridine (120 ml) and acetic anhydride (97 ml) at room temperature for 12 h gave penta-acetate (12) (33.1 g, 78) as needles, m.p.188-190 "C (from ethanol); -58", aamp;-61.5'7 a;amp; -74", ai!6 -170'3 a:amp; -418" (c 0.6, chloroform); Amx. 269 nm (20400); v,,,. 1730 (Mester), 1 625 (GN), 1 595,1495, and 815 cm-'(aromatic);ljH(CDC13) 1.88, 2.07, and 2.11 (each 3 H, each s, 3 x OAc), 2.02 (6 H, s, 2 x OAc), 3.48 (3 H, s, OMe), 3.47 (1 H, t, J9.6 Hz, 2-H), 3.68 (1 H, dd, J2.3,9.7 Hz, 5-H),4.00 (1 H, dd, J7.7,13.3 Hz, 7-H'), 4.38 ester), and 1 570 and 1 495 cm-' (NH;); 6H(CD3),SO 1.96, 2.00,2.02,2.04, and 2.21 (each 3 H, each s, 5 x OAc), 3.57 (1 H, t, J9.7 Hz,2-H), 3.96-4.32 (3 H, m, 5-H and 7-H2), 4.91 (1 H, t, J9.7Hz,4-H),5.1~5.30(1H,m,6-H),5.42(1H,t,J9.7Hz,3-H), 5.96 (1 H, d, J9.0 Hz, 1-H), and 9.03 (1 H, m, NH) (Found: C, 44.7; H, 6.0; N, 3.1. C17H26C1NOll requires C, 44.79; H, 5.75; N, 3.07).1,3,4,6,7-Penta-O-acetyl-2-deoxy-2-isothiocyanato-a-D-glycero-L-gluco-heptopyranose(15).-To a mixture of com-pound (13) (5.4 g, 12.0 mmol), chloroform (90 ml), calcium carbonate (4.1 g, 40.8 mmol), and water (40 ml) was added thiophosgene (15 ml, 19.0 mmol). The mixture was stirred vigorously for 48 h and then filtered. The organic layer was washed with water, dried (CaCl,), and evaporated to dryness. The residue was crystallised from ether (3.6 g, 65). Recrystallisation from ether gave the title isothiocyanate, m.p. 136138 "c, Calk2 -23'9 a1338 -25", a:amp; -29'9 ai$6 -53.5", and a$25 -90" (c 1.0, chloroform); A,,,.246 nm (7 300); vrnax.2 100 (NCS) and 1740 an-' (G=Oester); (CDCl,) 2.01, 2.05, 2.09, 2.11, and 2.20 (each 3 H, each s, 5 x OAC), 3.93 (1 H,dd, J2.2,10.0Hz, 5-H),4.00(1 H,dd, J8.6, 9.2 Hz, 2-H), 4.10 (1 H, dd, J8.0, 12.0 Hz, 7-H'), 4.27 (1 H, dd, J 6.0, 12.0 Hz, 7-H), 5.00 (1 H, t, J 10.0 Hz, 4-H), 5.28 (2 H, m, 3- and 6-H), and 5.65 (1 H, d, J 8.6 Hz, 1-H) (Found: C, 47.25; H, (1 H,dd, J5.7,13.3 Hz, 7-H), 5.13 (1 H, t, J9.7 Hz,4-H), 5.27- 5.1; N, 2.8. C18H23N01 1S requires C, 46.85; H, 5.02; N, 3.03). 5.41(1H,m,6-H),5.42(1H,t,J10.0Hz,3-H),5.88(1H,d,J8.3Hz, 1-H), and 8.18 (1 H, s, CH=) (Found: C, 55.8; H, 6.0; N, 2.7. C2SH31N012requires C, 55.86; H, 5.81; N, 2.61).1,3,4,6,7-Penta-O-acetyl-2-amino-2-deoxy-a-~-glycero-L-gluco-heptopyranose Hydrochloride (13).-A boiling solution of compound (12) (20.0 g, 37.2 mmol) in acetone (100 ml) was treated with SM-hydrochloric acid (8.5 ml); immediately, a white solid was formed. Crystallisation was completed by dilution with ether (100 ml) and further refrigeration (16.6 g, 98). This product decomposes above 209 "C without melting; a;' -5.5", a:;8 -4.6", aamp;j -6", a:i6 -1o.so, and oramp; -16" (c 0.6, pyridine); v,,,. 3 180-2 500 (NHZ), 1 745 (GO General Procedure for the Preparation of Compounds (16)- (28).-To a solution of a sugar isothiocyanate (1.3 mmol) in pyridine (6 ml) was added the appropriate aminosugar (1.3 mmol).The solution was stored at room temperature for 24 h and then poured into ice-water; the resulting white solid was collected. If the precipitation failed, the aqueous solution was extracted with dichloromethane (3 x 50 ml). The extracts were repeatedly washed with 2w-hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and water, dried (MgS04), and evaporated to dryness. The residue was crystallised from an appropriate solvent. According to this general procedure, the following products were prepared. N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-a-~-glucopyrano-san-2-yl)-N'-(2,3,4,6-tetra-0-acetyl-p-~-glucopyrunosyl)-thiourea(16). From compounds (3) and (5) (7379,m.p. 206-208"C (decomp.) (from ethanol); a;2 +58", a;amp; +60", aamp; +68",a:amp;j + 112.5", and a$amp; + 176.5" (c 1.0, chloroform); A,,,.249 nm (11 300); v,,,. 3 350 (NH),1 745 (GO),and 1530cm-' (NH)(Found: C,47.6;H,5.7;N,3.7. C29H40N208s requires C,47.28;H,5.47;N,3.80).N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-~-~-glucopyrano-san-2-yl)-N'-( ~-D-glucopyrunosyl)-2,3,4,6-tetra-0-acetyl-thiourea(17). From compounds (4) and (5) (8679,m.p. 175-176"C(lit.," 178"C).N-(1,3,4,6,7-Penta-O-acetyl-2-deoxy-~-~-glycero-~-gluco-heptopyranosan-2-yl)-N'-(2,3,4,6-tetra-O-acetyl-p-D-glucopyranosy1)thiourea (18). From compounds (14) and (5) (59), m.p. 126128deg;C (from ethanol); Cali8 -24.5", a;!amp; -25", a;amp; -27.5", aamp; -30.5",and+ 17.5" (c 1.0,chloroform); A,,,. 245 nm (11 100); vmax.3 350 (NH),1 745 (GO),and 1530 cm-I (NH)(Found: C,47.8;H, 5.5; N, 3.3. C32H44NZ020Srequires C,47.52;H, 5.48;N,3.46).N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-$-~-glucopyrano-san-2-yZ)-Nf-(2,3,4-tri-O-benzoyl-~-~-ribopyranosyl)-thiourea(19). From compounds (6) and (2) (5773,m.p. 203-205"C (decomp.) (from ethanol); a2d) -3S0, aamp; -3", a;amp; -3.5", -0")and + 29"(c 1.0,chloroform);A,,,. 249nm (12OOO); vmx. 3 390(NH),1 765(M),and 1 540 cm-' (NH)(Found: C,57.75;H,5.0; N,3.2. C41H42N2016S requires C,57.88;H, 4.98;N,3.29).N-(1,3,4,6,7-Penta-O-acefyl-2-amp;oxy-a-~-glycero-~-gluco-heptopyranosan-2-yl)-N'-(2,3,4-tri-O-benzoyl-p-D-ribopyranosy1)thiourea (20). From compounds (6)and (13)(99),m.p. 177-179 "C(decomp.) (from aqueous methanol); ah8 +17",a;f8 +19", +22.5", aamp; +56", and aJ$z5+ 158" (c 0.5, chloroform); Am=.247 nm (19600); vma. 3 370(NH),1 765,l 740 (GO),and 1 550 cm-' (NH)(FoundC,57.35;H,5.0; N,2.9.C44H46N2018Srequires C,57.26;H, 5.02;N,3.03).N,N-Bis-(1,3,4,6-tetra-O-acety1-2-deoxy-a-~-gluco-pyranosan-2-y1)thiourea(21). From compounds (3) and (1) (5 l), m.p. 219-220 "C(decomp.) (from ethanol); Calk3+ 82", a;s8+ 86",a)$amp; +97", + 147.5",and a;amp; + 179"(c1.0,chloroform); Am,. 248 nm (8 OOO); vmx. 3 320(NH),1 760, 1 740(GO),and 1 545cm-1 (NH)(Found C,47.7;H,6.0;N,3.5. C29H40N2018S-amp;H50H requires C,47.43;H,5.70;N,3.69).N,N'-Bis-(1,3,4,6-tetra-O-acety1-2-deoxy-~-~-glucopy-ranosan-2-y1)thiourea(22). From compounds (4) and (2) (82), m.p. 175-177 "C(lit.,23172-173 "C).N-(1,3,4,6-Tetra-O-acetyl-2-deoxy-a-~-glucopyrano-san-2-yl)-N-(1,3,4,6-tetra-0-acetyl-2-amp;oxy-$-D-gluco-pyranosan-2-y1)thiourea(23). From compounds (4) and (1)(65),m.p.173-174 "C(from ethanol), ak3 +43.5",aamp; +44", aamp; +49", +66",and a;amp; +48" (C 1.0, chloroform); Am=. 248 nm (11200); vmx. 3 350 (NH), 1755 (GO),1 550 and 1 540 cm-' (NH)(Found: C,47.0;H,5.45;N,3.5.C29H40N2018Srequires C,47.28;H, 5.47;N,3.80).N,N'-Bis-(1,3,4,6,7-penta-O-acety1-2-deoxy-~-D-gly-cero-~-gluco-heptopyranosun-2-yl)thiourea(24). From com-J. CHEM. SOC. PERKIN TRANS. 1 1990 +94.5",and a$amp; +195" (c 1.0,chloroform); h,,,. 246 nm (11 200);vmx. 3 340(NH),1 760(GO),and 1 550 cm-' (NH)(Found: C,47.4;H,5.8;N,3.1).N-(1,3,4,6,7-Penta-0-acetyl-2-deoxy-a-~-glycero-~-gluco-heptopyranosan-2-yl)-N'-(1,3,4,6,7-pentu-O-acetyl-2-deoxy-~-D-glycero-L-gluco-heptopyranosan-2-y~)thio-urea(26). From compounds (15) and (10) (51), m.p.176-178"C(decomp.) (from aqueous methanol); Cali6 -5", a;:8 -5.5", -5", a:s6 +8.5", and afZs +63.5" (c 1.0, chloroform); Am=+ 245 nm (11 500);v,,,. 3 370 (NH),1 755 (GO),and 1 540cm-I (NH)(Found: C, 47.4; H,5.6;N,3.1).N-(1,3,4,6,7-Pentu-O-acetyl-2-deoxy-P-D-glycero-L-gluco-heptopyranosan-2-yl)-N'-(1,3,4,6-tetra-O-acetyl-2-deoxy-a-~-glucopyranosan-2-yl)thiourea(27). From com-pounds (3) and (10) (48),m.p. 212-213 "C(decomp.) (from ethanol); a;6 + 12S0,a;:8 + 12.5", + 14.5",a:;6+26",and a$d5 +45" (c 1.2,chloroform); A,,,.244 nm (11OOO); v,,,. 3 380,3 320 (NH),1 760(GO), and 1 560cm-' (NH)(Found: C,47.5;H,5.5;N,3.2.C32H44N2020Srequires C, 47.52;H,5.48;N,3.46).N-(1,3,4,6,7-Penta-O-acetyl-2-deoxy-a-~-glycero-~-gluco-heptopyrunosan-2-yl)-N'-(1,3,4,6-tetra-O-acetyl-2-deoxy-~-~-glucopyranosan-2-yl)thiourea(28). From com-pounds (4) and (13) (5379,m.p. 176-178 "C(decomp.) (from methanol); a;6 + 19.5", + 20.5",aamp; + 23.5",aamp;+42",and afz5+69" (c 1.0,chloroform); A,,,. 246 nm (10600);v,~. 3 360(NH),1 760(GO),and 1 555 cm-' (NH) (Found: C,47.7;H,5.6; N,3.4). Acknowledgements The present work was financed by CICYT(No. 860255). References 1 M. H.Ryder, M. E. Tate, and G. P. Jones, J. Biol. Chem., 1984,259, 9704. 2 M. Akagi, S. Tejima, and M. Haga, Chem. Pharm. Bull., 1961,9,360; L. A. Reed 111and L. Goodman, Carbohydr. Res., 1981, 94, 91; 0. Kanie, J. Nakamura, M. Kiso, and A. Hasegawa, J. Carbohydr. Chem., 1987,6,105. 3 H. Paulsen and K. Pflughauot, in 'The Carbohydrates,' eds. W. Pigman and D. Horton, Academic Press, New York, 1980, Vol. IB, p. 881; K. Linek, J. Aroldi, and J. Defaye, Carbohydr. Res., 1987, 164, 195; J. M. J. Tronchet, N. Bizzozero, and F. Barbalat-Rey, J. Carbohydr. Chem., 1987,6,155. 4 D. Rouzaud and P. Sinay,J. Chem. SOC., Chem. Commun., 1983,1353; B. Giese and T. Witzel, Angew. Chem., Int. Ed. Engl., 1986,25,450; S. A. 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Plumet, submitted for publication in Tetrahedron Lett. 40 M. Avalos, R. Babiano, P. Cintas, J. Fuentes, J. L. Jimenez, and J. C. Palacios, Heterocycles, 1989,29, 1; M. Avalos, R. Babiano, P. Cintas, J. L. Jimtnez, and J. C. Palacios, unpublished work. Received 27th June 1989; Paper 9/02710F