A new approach to the synthesis of substituted 4-imidazolidinones as potential antiviral and antitumor agents

TETRAHEDRON Tetrahedron 54 (1998) 4859-4872

Pergamon

A New Approach to the Synthesis of Substituted 4-Imidazolidinones as Potential Antiviral and Antitumor Agents

A h m e d I. K h o d a i ~ t'* Chemistry Department, Faculty o f Education, Tanta University (Kafr El-Sheikh Branch), Tanta, Egypt.

and Philippe Bertrand b bLaboratoire de Chimie Xll, Universitd de Poitiers et CNRS, 40 Avenue du Recteur Pineau, 86022 Poitiers, France.

Received l0 October 1997; accepted 17 February 1998

Abstract: 5-((Z)-Arylidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinones 7a-d and 5-((Z)-

arylidene)-2-((2-(E)-polyhydroxyalkylidene)hydrazono)-4-imidazolidinones lla-d to 15a-d were prepared from the reaction of 5-((Z)-arylidene)-2-methylmercaptohydantoins 3a-d with 2-(E)benzylidene hydrazone 6 or 2-(E)-monosaccharides hydrazones 9a-e, which in turn were prepared by condensation of benzaidehyde or appropriate monosaccharides 8a--e with hydrazine hydrate. AMI semi-empirical calculations reveal that the azine system is favoured with a trans geometry and planar conformation for CfN-NfC. All the new compounds were tested for their potential antiviral and antitumor activities. © 1998 Elsevier Science Ltd. All rights reserved. A number o f 4-imidazolidinone derivatives display a wide range o f biological properties, including anticonvulsant, 1 antidepressant, 2 antiinflammatory, 3"5 antiviral, 6"s antitumor 9 and platelet inhibitory activities, I° and are a conspicuous structural feature o f several inhibitors o f aldose reductase. ~1.12 In this respect, it seemed worth-while to link the imidazolidinone to an hydrophilic moiety such as a glycoside. It was thus anticipated a better water solubility o f these beterocycles and an improved selectivity toward cancer cells which are known to be specifically enriched in carbohydrate receptors such as lectins. 13'~4 H

OH

RI

~1 ~ N"*N

H

11a-d = D-IPtbCto IZs-d = D-gluco

13a-d = D-mnno 14a-d ffiL-arabino 15a-d ffiD-xylo

H ~=N ~N

Ph

7a-d

a : A r = C6Hs

b : Ar = 4 - M ~ c : Ar ffi4-Mt<)C'~H. d : Ar ffi4-CIC6H4

Structures such as l l a - d to 15a-d were selected and their synthesis planned via the anticipated coupling o f these two moieties by an azine unit. Indeed the preparation o f simpler analogs such as 7a-d was first studied * Present address: Laboratoire de Chimie XI1, Universitd de Poitiers et CNRS, 40 Avenue du Recteur Pineau, 86022 Poitiers, France, Far: O0 33 05 49 45 35 01, E-mail: [email protected]

0040-40201981519.00 © 1998 Elsevier Science Ltd. All rights reserved. PH: S0040-4020(98)00170-7

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in order to test two synthetic pathways (vide infra) and the possible tautomerie equilibrium of such structures (notwithstanding the two azine isomers). Moreover, a number of 2-(alkylidenehydrazono)-4-imidazolidinone derivatives have been found to be useful inhibitors of the Malllard reaction in vitro and, as such, are potentially useful in the treatment of diseases caused by this reaction such as disorders associated with diabetes and aging. They also have hypoglycemic activity, and are characterized by a long-lasting activity, excellent adsorption properties, low toxicity and high stability ~s'16. Retrosynthetic analysis shows that arylazinoimidazolidinones 7 and 11-15 could be prepared using two different strategies (Scheme 1). Path A relies on the condensation of an aldehyde with an imidazolohydrazine, which may be prepared from the reaction of a methylthio derivative 3 with hydrazine hydrate. These steps are inverted in path B which is based on the condensation of an aldehyde hydrazone with the already mentioned methylthio derivative 3. H

A

HN~NH

H

H

~N -N 4

H I~NH H N

B

7 : R--CsHs 11-15 : R= (CHOH)aCH2OH

H

.,y.. $Me

3 Scheme 1

RESULTS AND DISCUSSION

The present work describes the synthesis, conformational analysis and biological testing of unreported series of 5-((Z)-aryfidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinones 7a-d and 5-((Z)-arylidene)-2((2-(E)-polyhydroxyalkylidene)hydrazono)-4-imidazofidinones l l a - d to 15a-d. First path A was considered. The condensation of aromatic aldehydes with 2-thiohydantoin 1 by refluxing in a solution of sodium acetate and acetic acid afforded 5-((Z)-arylidene)-2-thiohydantoins 2a-d, which upon methylation gave the corresponding 5-((Z)-arylidene)-2-methylmercaptohydantoins 3a-d? 7 In our hands these compounds could be conveniently prepared in one pot by the reaction of compound 1 with aromatic aldehydes in presence of sodium methoxide followed by the addition of iodomethane at room temperature. According to path A, when 3a-d were heated with hydrazine hydrate in boiling acetic acid until the evolution of methane thiol could not be

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detected, the corresponding N,N-bis-(5-(Z)-arylidene-4-oxo-2-imidazolidinylidene)hydrazines 5a-d were obtained instead of the anticipated 5-((Z)-ary~dene)-2-hydrazono-4-imidazolidinones4a-d. I~ The structures o f 5a-d were confirmed on the bases of elemental analysis and spectral data (IR, ~H NMR and MS). The IR absorption spectra of compound 5a was characterised by the absence o f signal for NH2 group at 3350 cmq and the presence of signal at 1730 cml due to the carbonyl groups in addition to the NH groups at 3145 cml . The JH NMR spectrum of compound 5a showed a singlet at fi 6.75 ppm assigned to the vinyl proton, indicating the presence of a Z-configuration for the exocyclic double bond, in agreement with the ~H NMR spectra of 5-(E)- and 5-(Z)-arylidenehydantoin derivatives whose vinyl protons respectively appear at 8 6.10-6.35 and 6.40-6.75 ppm) s-2°

H /_.__~O

HN~NH S

ArCHO, AcONa,

H~,,NH S

AcOH, reflux

H

2a-d

i l. ArCHO,MeON~A r ~ 2. Mel

0

N~NH

ql

aq. NaOH MeOH,Mel

SMo 3a-d N2H4.H20, AcOH, reflux

b : Ar = 4-MeC.#t4

N~ 2 4a-d

e : Ar = 4-MeOCq,H4 d : Ar = 4-CIC#t4

H

H 5a-d

Scheme 2 As path A gives only compounds 5a-d, we turned our attention to the use of aldehyde hydrazones according to path B. So, 2-(E)-benzylidene hydrazone 6 was prepared following the method of Lock2r via the reaction o f hydrazine hydrate and benzaldehyde in ethanol at room temperature. Compound 6 was condensed with 5-((Z)-arylidene)-2-methylmercaptohydantoins3a-d to give 5-((Z)-arylidene)-2-((2-(E)-benzylidene)hydrazono )-4-imidazolidinones 7a-d. The structures of 7a-d were established on the basis of their elemental analysis and spectral data (IR, JH NMR, J3C NMR and MS). The singlet observed at ~ 6.40 ppm for the corresponding vinylic proton is better in

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agreement with a Z-configuration of the double bond and this is confirmed by the ;3C NMR spectrum which shows a singlet at 108.90 pprn. The corresponding carbon for 5-(Z)- and 5-(E)-arylidenehydantoin derivatives respectively give signals at 6 105-112 ppm and 113-120 ppm. '8"2° thN--Nth.~O

+

H~==N~NITa

EtOH, r.t.

HX]==O 0045

/

H

C6Hs 6

H

H

SMe

1

J~

CsHs

3a-d

>

HN,~NH

a : A r = C 6 H s ; b : A r = 4-MeC_6H4; e : A r ffi 4 - M e O C 6 I ~ ; d : A r ffi 4-CIC6H4

Scheme 3 At this stage, calculations at the AM1

l e v e l 22 w e r e

considered in order to determine the relative energies

of the possible tautomeric forms. These also allow to determine the relative energies of the E and Z isomers of arylldenehydantoin derivatives. It was found that the Z-isomer is more stable by 3 kcal/mol for 7a and thus no double bond isomerisation is anticipated. For compound 7a, the 3 tautomeric forms ct, T and 8 and the azine isomer 13 were considered. As expected ordy a small energy difference exists between the azine isomers, but tautomers T and 8 were found to be much less stable and can be ruled out (Figure 1).

Ph es ~ / / O

HIN~2"H

Ph e

HIN~2"H

Ph s

1N~22NH

Ph e

H1"~,~N

(0) 13(+0,1) T (+11,6) ~ (+16,9) Figure 1. Relative energies (kcal/mol) ofazine isomers (ct and 13) and tautomers (~/and 8) for 7a. According to the literature (X-Ray data), 23~4 the azine conformation may be transoid or gauche (with a torsion angle of 10 to 30°). An out of plane twisting of the phenyl ring with respect to the H-C--N plane ofc.a. 350("` 5 °) is usually observed for Ph-CH=N-N moiety with bond distances of 1.27-1.30 A (CH=N) and 1.40 A (N-N). From AM1 calculations, the bond distances (C--N: 1.33/~, N-N: 1.34 • and ArC=N: 1.30 A), as well as

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A. L Khodair, P. Bertrand/Tetrahedron 54 (1998)4859-4872

the twisting of the aromatic ring at C-9 (30 °) with respect to each C=N bond, were found in agreement with these data. A twisting of c.a. 37 ° between the aromatic ring and the C-5, C-6 double bond is also found. Finally, a s-trans azine conformation is always more stable, the [3 isomer being almost planar while the ¢t one is

slightly distorded (C=N-N=C torsion angle : 177° for 13and 160 ° for ct). The synthesis of compounds 11-15 was then carried out. For the synthesis of monosaccharides hydrazones, it is known that under specific conditions, the open chain form 9 could be obtained without formation of ring form 10. 25 We found that monosaccharides 8a-e including D-galactose, D-glucose, Dmannose, L-arabinose and D-xylose could be condensed with hydrazine hydrate in anhydrous methanol to afford 2-(E)-monosaccharides hydrazones 9a-e.

--N,,,Nt~

I,,12N-- NI,.Iz.I,,12O +

'

~

~

OH

MeOH r.t.

9a-e

Rt

b: ntJZ3 =

OH, n2,1~ = H, ~ = CH2OH, D ~ c o

10a-e

gpR4 = H, I~,R3 ffiOH, 1~ ffiCH2OH,D-mnno d: RI,R4 -- OH, I~,R3 ffiH, !~ ffiH, L-arabino

c:

e:

RtJZ3 ffiOH, ~

= H, ~ - H, a-xylo Scheme 4

The structures of 9a-e were confirmed on the bases of their elemental analysis and spectral data (IIL mH NMlL m3CNMR and MS). The structure ofga was suported by its mass spectra, which showed a molecular ion peak at m/z 194 and its 1H NMR spectrum showed the anomeric proton as a doublet at 7.05 ppm withJ = 7.50 Hz, corresponding to the orientation of H-1 and H-2 protons. The triplet at 4.40 ppm was due to H-2, indicating the presence of only the E-configuration in accordance with the reported results for D-ribose Ehydrazone and D-ribose Z-hydrazone which showed signals for H-l, H-2 at 6.70-7.40, 4.10-4.70 ppm and 6.50-6.80, 4.80-5.30 ppm, respectively. 26'27The singlet at 6.05 ppm was due to NH2. The ~3C NMR spectrum of compound 9e was characterized by a singlet at 144.46 ppm (C-1), indicating the presence of only the Econfiguration of the open chain form. Consequently, the corresponding glycosylhydrazines 10a-e were not obtained. The reaction of 9a-e with equimolar amount of 3a-d was effected by heating in methanol to give the corresponding 2-((2-(E)-polyhydroxyalkylidene)hydrazono)- 5-((Z)-arylidene)-4-imidazolidinones

11-15. The

structures of 11-15 were established on the basis of their elemental analysis and spectral data (IlL IH NMR, J3C

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NMR and MS). Analytical data for compound l l a revealed a molecular formula Ci6H20N406 (m,/z 364). The IH NMR spectrum ofcornpound l l a showed the presence o f a singlet at 6.40 ppm assigned to the vinylic proton, proving Z-eontiguration of the exocyelic double bond. The doublet at 7.25 ppm was due to H - I ' and the multiplet at 4.50 ppm assigned to H-2', in agreement with E-eortfiguration of the other exoeyclic double bond. H

H

H

Y SMe

EtOH, reflux

R,

J

3a-d

RI 11a-d- 15a-d

1 l a - d = D-galacto 12a-d = D-gluco 13a-d = D-manno 14a-d = L-arabino 15a-d = D-xylo

a: Ar = C6H5 b: Ar = 4-MeC6H4

c: Ar = 4-MeOC6H4 d: Ar = 4-C1C6I-h Scheme 5

In conclusion, we have described the successful synthesis of glyco- and benzylidenehydrazonoimidazolidinone derivatives and the confirmation o f their most stable conformation by molecular modelization. Those compounds were submitted to antiviral and antitumor preliminary tests. For antiviral activities, all new compounds 7a-d and l l a - d to 15a-d were tested against HIV-1 (HTLV IIIB) in MT-4 cells and were found to he inactive.28 For antitumor activities, the 20 compounds ( l l a - d to 15a-d) were screened against leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer. 29 Only compounds 12d and 13a showed enough activity to be further tested in additional tumor systems.

EXPERIMENTAL SECTION

General. Melting points (°C, uncorrected) were recorded on a GaHenkamp melting point apparatus. Aluminum

sheets coated with silica gel 60 F254 (Merk) were used for TLC. Detection was effected by viewing under a short wavelength UV lamp. IR spectra (KBr disc) were obtained on a Pye Unicam Spectra 1000. ~H NMR spectra were measured on a Wilmad 270 MHz and a Bruker Advance DPX 300 MHz spectrometers for solutions in DMSO-d6 using TMS as internal standard and the chemical shifts are given as 8 values and the d values are given in Hz. Mass spectra were recorded on a Varian MAT 112 spectrometer. Analytical data were obtained from the Service Central de Microanalyse (CNRS, Lyon). 2-(E)-Benzylidene hydrazone 6 was prepared according to the published method 2m for the preparation of arylidene hydrazones by reaction o f benzaidehyde with hydrazine hydrate.

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General procedure for the reaction of hydrazine hydrate with (3a-d). The standard procedure was used) 7 A mixture of each 3a-d 17 (10 mmol) and a slight excess of h y d r ~ hydrate (0.55 g, 11 mmol) in glacial acetic acid (2 ml) was refluxed for 4 h. After cooling, the separated solid was washed with ethanol and recrystallized from dimethylformamide to give N,N-bis-(5-(Z)- arylidene-4-oxo-2imidazo lidinylidene)hydrazines 5a-d. N,N-Bis-(5-(Z)-benzylidene-4-oxo-2-imidazolidinylidene)hydrazine (Sa): Yield 2.53 g (68%), yellow crystals, mp >300 °C; IR: v 3145 cm~ (NH), 1730 cm~ (CO); tH NMR: G 6.75 (s, 1H, HC=C), 7.42 (m, 3H, At-H), 8.15 (m, 2H, At-H), 11.20 (s, 1H, NI-H), 11.70 (s, IH, N3-H); MS, m/z = 372 (M+); Anal. Calcd. for C20Hm6N602(372.39): C, 64.50; H, 4.33; N, 22.57. Found: C, 64.27; H, 4.56; N, 22.45. N,N-Bis-(5-(Z)-(4-methylbenzylidene)-4-oxo-2-imidazolidinylidene)hydrazine (5b): Yield 3.11 g (72%), yellow crystals, mp >300 °C; IR: v 3148 crn~ (NH), 1728 cm~ (CO); ~H NMR: G 6.82 (s, 1H, HC=C), 7.46 (d, 2H, Ar-H), 7.81 (d, 2H, Ar-H), 11.15 (s, 1H, NI-H), 11.75 (s, 1H, N3-H); MS, m/z = 400 (M+); Anal. Calcd. for C22H20N602 (400.44): C, 65.98; H, 5.03; N, 20.99. Found: C, 65.72; H, 5.33; N, 21.20. N,N-Bis-(5-(Z)-(4-methoxybenzylidene)-4-oxo-2-imidazolidinylidene)hydrazine (5c): Yield 2.81 g (65%), yellow crystals, mp >300 °C; IR: v 3148 crn~ (NH), 1728 cm~ (CO); ~H NMR: G 6.78 (s, 1H, HC=C), 7.18 (d, 2H, Ar-H), 7.93 (d, 2H, Ar-H), 10.76 (s, IH, N~-H), 11.65 (s, IH, N3-H); MS, m/z = 432 (M+); Anal. Calcd. for C22H20N604 (432.44): C, 61.10; H, 4.66; N, 19.43. Found: C, 60.87; H, 4.71; N, 19.28. N,N-Bis-(5-(Z)-(4-chlorobenzylidene)-4-oxo-2-imidazolidinylidene)hydrazine (Sd): Yield 3.03 g (69%), yellow crystals, mp >300 °C; IR: v 3140 cm~ (NH), 1727 cm1 (CO); ~H NMR: G 6.90 (s, 1H, HC=C), 7.47 (d, 2H, Ar-H), 7.85 (d, 2H, At-H), 10.84 (s, 1H, Nt-H), 11.70 (s, 1H, N3-H); MS, m/z = 440 (M+); Anal. Calcd. for C20Ht4C12N604 (441.28): C, 54.43; H, 3.20; N, 19.05. Found: C, 54.66; H, 3.43; N, 18.87. General procedure for the preparation of 5-((Z)-arylidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinones (7a-d). A mixture of 5-((Z)-arylidene)-2-methylmercaptohydantoins

3a-d m7 (10 mmol) and 2-(E)-benzaldehyde

hydrazone 6 (1.2 g, 10 mmol) in ethanol (30 ml) was heated under reflux for 48 h. After cooling, the separated solid was collected and recrystallized from ethanol to give 7a-d. 5-((Z)-Benzylidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinone (7a): Yield 2.2 g (76%), yellow crystals, mp 236-238 °C; IR: v 3134 emt (NH), 1727 cm"1 (CO); 1H NMR: G 6.42 (s, 1H, HC=C), 7.20-7.95 (m, 10H, Ar-H), 8.25 (s, 1H, HC=N), 11.30 (br. s, 1H, Nt-H), 11.80 (s, 1H, N3-H); ~3C NMR: G 108.90 (HC=C), 127.52, 127.74, 128.40, 128.49, 129.34, 129.66, 134.12, 134.84 (C-Ar and C-5), 155.54 (C-2), 158.00 (HC=N), 166.81 (C-4); MS, m/z = 290 (M+); Anal. Calcd. for C~7H~4N40 (290.32): C, 70.33; H, 4.86; N, 19.30. Found: C, 70.25; H, 5.00; N, 19.10.

5-((Z)-Methylbenzyfidene)-2-((2-(E)-benzylidene)hydrazoao)-4-imidazofidinone

(7b): Yield 2.1 g (69%),

yellow crystals, mp 224-226 °C; IR: v 3145 cm~ (NH), 1730 cm"~ (CO); ~H NMR: G 2.85 (s, 3H, Me), 6.68 (s,

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1H, HC=C), 7.58-8.45 (m, 10H, Ar-H and HC=N), 11.25 (br. s, IH, N1-H), 11.75 (s, 1H, N3-H); 13C NMR: 8 109.83 (HC=C), 124.75, 126.90, 127.83, 128.02, 130.40, 132.60, 133.25, 134.07, 139.01 (C-At, C-5), 159.85 (C-2), 165.14 (C-4), 169.90 (HC=N); MS m/z = 304 (M+); Anal. Calcd. for C]aH16N40 (304.35): C, 71.03; H, 5.30; N, 18.41. Found: C, 70.87; H, 5.46; N, 18.33.

5-((Z)-Methoxybenzylidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinone (7e): yield 2.3 g (72%), yellow crystals, mp 161-163 °C; IR: v 3145 cm"~ (NH), 1730 cm"1 (CO); IH NMR: 8 3.70 (s, 3H, OMe), 6.48 (s, 1H, HC=C), 7.30-7.90 (m, 9H, Ar-H), 8.25 (s, 1H, HC=N), 11.20 (br. s, 1H, NI-H), 11.72 (s, 1H, NrH); MS, m/z = 320 (M+); Anal. Calcd. for C~sH~6N402(320.35): C, 67.48; H, 5.03; N, 17.49. Found: C, 67.30; H, 5.25; N, 17.62.

5-((Z)-Chlorobenzylidene)-2-((2-(E)-benzylidene)hydrazono)-4-imidazolidinone (7d): Yield 2.4 g (74%), yellow crystals, rap 250-252 °C; IR: v 3140 cmt (NH), 1725 cm"~ (CO); ~H NMR: 6 6.56 (s, IH, HC=C), 7.25-7.90 (m, 9H, At-H), 8.25 (s, 1H, HC=N), 11.25 (hr. s, 1H, NI-H), 11.75 (s, IH, N3-H); MS, tn/z = 325

(M+); Anal. Calcd. for CI7HI3CIN40(324.77): C, 62.87; H, 4.03; N, 17.25. Found: C, 62.66; H, 4.30; N, 17.38.

General procedure for the preparation of 2-(E)-monosaeeharides hydrazones (9a-e). A mixture of monosacchaddes 8a-e (10 mmol) (D-galactose, D-glucose, D-marmose, L-arabinose or D-xylose) and hydrazine hydrate (0.5 g, 10 mmol) in methanol (30 ml) was stirred at room temperature for 24 h. The solid product was filtered offand recrystalliTed from methanol to give 9a, 9e and 9d, as white solids. Products 9b and 9e were obtained as colorless oils aRer evaporating the mixture to dryness under reduced pressure. 2-(E)-D-Galaetose hydrazone (%): Yield 1.80 g (93%), white crystals, mp 125-127 °C (lit.2s rap 140-142°; 62%); IR: v 3306 cm"~ (OH, NH2), 1671 cm~ (C=N). IH NMR: 8 3.30-3.50 (m, 4H, 6-H, 6'-H, 5-H, 4-H), 3.67 (d, 1H, J = 7.32 Hz, 6-OH), 4.15 (m, 3H, 3-H, 4-OH, 5-OH), 4.30 (d, 1H, J = 7.30 Hz, 3-OH), 4.40 (m, 1H, 2-H), 4.50 (d, 1H, J = 7.78 Hz, 2-OH), 6.05 (s, 2H, NH2), 7.05 (d, 1H, J = 7.52 Hz, l-I-I); MS, m/z = 194 (M+); Anal. Calcd. for Cd-Im4N205(194.19): C, 37.11; H, 7.26; N, 14.43. Found: C, 36.92; H, 7.38; N, 14.50. 2-(E)-D-Glueose hydrazone (gb): Yield 1.88 g, (97%), colorless oil; (lit.25 mp 101-103, 5%); IR: v 3308 cml (OH, NH2), 1675 cm] (C=N); ~H NMR: ~ 3.25-3.47 (m, 4H, 6-H, 6'-H, 5-H, 4-H), 3.65 (d, 1H, 6-OH, J = 7.30 Hz), 4.15 (m, 3H, 3-H, 4-OH, 5-OH), 4.30 (d, 1H, J = 7.25 Hz, 3-OH), 4.38 (m, 1H, 2-H), 4.50 (m, IH, 2-OH), 6.05 (s, 2H, NH2), 7.05 (d, 1H, J = 7.30 Hz, l-H); MS, m/z = 194 (M+); Anal. Calcd. for C6H14N205 (194.19): C, 37.11; H, 7.26; N, 14.43. Found: C, 37.30; H, 7.15; N, 14.36. 2-(E)-D-Mannose hydrazone (9e): yield 1.78 g (92%), white crystals; mp 130-132 °C (lit.2s mp 144°, yield 68%); IR: v 3308 cm"~ (OH, NH2), 1670 cm"1 (C=N); 1H NMR: 8 3.30-3.60 (m, 4H, 6-H, 6'-H, 5-H, 4-H), 3.80 (t, 1H, J = 9.35 Hz, 6-OH), 4.10-4.60 (m, 5H, 3-H, 4-OH, 5-OH, 3-OH, 2-H), 4.80 (s, 1H, 2-OH), 6.10 (s, 2H, NH2), 7.00 (d, 1H, J = 7.25 Hz, l-H); J3C NMR: 8 63.49 (C-6), 69.58 (C-4), 70.17 (C-2), 70.32 (C-3),

A. !. Khodair, P. Bertrand/Tetrahedron 54 (1998)4859-4872

4867

72.64 (C-5), 144.46 (C-l); MS, m/z -- 194 (M+); Anal. Calcd. for C6H14N205 (194.19): C, 37.11; H, 7.26; N, 14.43. Found: C, 37.27; H, 6.92; N, 14.60. 2-(E)-L-Arabinos¢ hydrazone (9d): yield 1.48 g (90%), white crystals; mp 143-145 °(2 (lit.25 mp 122-124°, yield 62%); IR: v 3316 cm"1 (OH, NH~), 1654 cm1 (C=N); ~H NMR: ~ 3.25-3.45 (m, 3H, 5-H, 5'-H, 4-H), 3.50 (m, 1H, 5-OH), 4.15 (m, 1H, 3-H), 4.30 (m, 1H, 2-H), 4.38 (d, 1H, J = 10.00 Hz, 4-OH), 4.47 (d, IH, J = 7.60 Hz, 3-OH), 4.60 (d, 1H, J = 7.58 Hz, 2-OH), 6.10 (s, 2H, NH2), 7.05 (d, lH, J = 6.80 Hz, l-H); MS, m/z -- 164 (M+); Anal. Calcd. for CsH~2N204(164.16): C, 36.58; H, 7.37; N, 17.06. Found: C, 36.70; H, 7.58; N, 17.14. 2-(E)-D-Xylose hydrazone (9e): yield 1.54 g (94%), colorless oil, (lit. 25 mp 108-110°, yield 3%); IR: v 3315 cm~ (OH, NI-I2), 1656 cmt (C=N); IH NMR: 8 3.25-3.45 (m, 3H, 5-H, 5'-H, 4-H), 3.52 (m, 1H, 5-OH), 4.20 (m, 1H, 3-H), 4.30 (m, 18, 2-H), 4.43 (d, 18, J = 9.65 Hz, 4-OH), 4.47 (d, 1H, J = 7.50 Hz, 3-OH), 4.60 (d, IH, J = 7.85 Hz, 2-OH), 6.16 (s, 2H, NH2), 7.05 (d, 1H, J = 7.20 Hz, I-H); MS, m/z = 164 (M+); Anal. Calcd. for CsHI2N204 (164.16): C, 36.58; H, 7.37; N, 17.06. Found: C, 36.40; H, 7.46; N, 17.12. General procedure for the preparation of 5-((Z)-arylidene)-2-((2-(E)-polyhydroxyalkylidene)hydrazo-

no)-4-imidazolidinones (1 la-d-15a-d). A mixture of 5-((Z)-aryfidene)-2-methylmercaptohydantoins 3a-d 17 (10 mmol) and 2-(E)-monosaccharides hydrazones 9a-e (10 mmol) in methanol (30 ml) was heated under reflux for 72 h. Atter cooling, the separated solid was collected and recrystalliTed ~om dimethylformamide to give lla-d-15a-d respectively. 5-((Z)-Benzylidene)-2-((2-(E)-D-galaetose)hydrazono)-4-imidazolidinone (11a): Yield 2.73 g (75%), yellow crystals, mp 205-207 °C; IR: v 3438 cm"~ (OH), 3192 cm~ (NH), 1719 cm~ (CO); ~H NMR: ~ 3.253.45 (m, 2H, 6'-H, 6"-H), 3.60 (m, 2H, 5'-H, 4'-H), 3.75 (t, 1H, 6'-OH, J=7.50 Hz), 4.20 (m, 2H, 5'-OH,4'OH), 4.50 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.75 (d, 1H, 2'-OH, J =7.75 Hz), 6.35 (s, 1H, HC=C), 7.25 (d, 1H, I'H, J=7.55 Hz), 7.32-7.80 (m, 5H, At-H), 11.20 (br. s, 1H, N~-H), 11.60 (s, 1H, N3-H); MS, m/z = 364 (M+); Anal. Calcd. for CI6H20N406(364.36): C, 52.74; H, 5.53; N, 15.38. Found: C, 52.54; H, 5.71; N, 15.25.

5-((Z)-Methylbenzylidene)-2-((2-(E)-D-galactose)hydrazono)-4-imidazolidinone (lib): Yield 2.61 g (69%), yellow crystals; mp 218-220 °(2; lg: v 3435 cm"~ (OH), 3190 cm"~ (NH), 1720 cm~ (CO); ~H NMR: 8 2.30 (s, 1H, Me), 3.35-3.45 (m, 2H, 6'-H, 6"-H), 3.55 (m, 2H, 5'-H, 4'-H), 3.75 (d, 1H, J = 7.80 Hz, 6'-OH), 4.20 (in, 2H, 5'-OH, 4'-OH), 4.50 (m, 3H, 2'-H, 3'-H, Y-OH), 4.70 (d, 1H, J = 7.65 Hz, 2'-OH), 6.36 (s, 1H, HC=C), 7.00 (d, 1H, J = 7.50 Hz, I'-H), 7.50 (d, 2H, Ar-H), 7.70 (d, 2H, Ar-H), 11.00 (br. s, 1H, Nt-H), 11.52 (s, 1H, NrH); MS, m/z = 378 (M~); Anal. Calcd. for CITH22N406(378.38): C, 53.95; H, 5.86; N, 14.81. Found: C, 54.12; H, 5.96; N, 14.65. 5-((Z)-Methoxybeazylideae)-2-((2-(E)-D-galaetose)hydrazoao)-4-imidazolidinoae (lie): Yield 2.80 g (71%), yellow crystals; mp 203-205 °C; IR: v 3432 cmj (OH), 3193 cm"~ (NH), 1718 cm"~ (CO); ~H NMR: 6 3.30-3.45 (m, 2H, 6'-H, 6"-H), 3.60 (m, 2H, 5'-H, 4'-H), 3.75 (in, 4H, OMe, 6'-OH), 4.25 (m, 2H, 5'-OH, 4'OH), 4.50 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.72 (d, IH, J = 7.50 Hz, 2'-OH), 6.35 (s, IH, HC=C), 7.00 (d, IH, J

4868

A. L Khodair, P. Bertrand/Tetrahedron 54 (1998) 4859--4872

= 7.30 Hz, I'-H), 7.55 (d, 2H, Ar-H), 7.80 (d, 2H, At-H), 11.02 (br. s, 1H, N1-H), 11.56 (s, IH, NrH); MS, m/z = 394 (M*); Anal. Caled. for CITH22N407(394.38): C, 51.79; H, 5.62; N, 14.21. Found: C, 51.63; H, 5.84; N, 14.17.

5-((Z)-Chlorobenzylidene)-2-((2-(E)-D-galaetosejhydrazono)-4-imidazolidinone

(lid):

Yield 2.80 g

(70%), yellow crystals; mp 215-217 °C; IR: v 3435 cml (OH), 3196 cm"l (NH), 1725 cm"l (CO); IH NMR: 8 3.30-3.45 (m, 2H, 6'-H, 6"-H), 3.57 (m, 2H, 5'-H, 4'-H), 3.77 (t, 4H, J-- 7.47 Hz, 6'-OH), 4.20 (m, 2H, 5'OH, 4'-OH), 4.45 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.72 (d, 1H, J-- 7.25 Hz, T-OH), 6.35 (s, 1H, HC=C), 7.40 (d, 1H, J = 7.67 Hz, I'-H), 7.60 (d, 2H, At-H), 7.85 (d, 2H, Ar-H), 11.25 (br. s, 1H, N1-H), 11.75 (s, 1H, N3H); MS, m/z = 399 (IriS); Anal. Calcd. for CI6HI9CIN406(398.80): C, 48.18; H, 4.80; N, 14.05. Found: C, 47.94; H, 5.62; N, 13.89. 5-((Z)-Benzylidene)-2-((2-(E)-D-glueose)hydrazono)-4-imidazolidinone (12a): Yield 2.15 g (59%), red crystals, rap 195-197 °C; IR: v 3434 cm"~ (OH), 3194 em~ (NI-I), 1720 cm"~ (CO); 1H NMR: 6 3.25-3.45 (m, 2H, 6'-H, 6"-H), 3.65 (m, 2H, 5'-H, 4'-H), 3.75 (t, 1H, J = 7.50 Hz, 6'-OH), 4.25 (m, 2H, 5'-OH, 4'-OH), 4.50 (m, 3H, 2'-H, 3'-H, T-OH), 4.75 (d, 1H, J = 7.60 Hz, T-OH), 6.35 (s, 1H, HC--C), 7.25 (d, 1H, J = 7.45 Hz, I'-H), 7.30-7.76 (m, 5H, At-H), 11.15 (br. s, IH, N~-H), 11.60 (s, 1H, N3-H); MS, m/z -- 364 (M+); Anal. Calcd. for C~6H20N406(364.36): C, 52.74; H, 5.53; N, 15.38. Found: C, 52.52; H, 5.84; N, 15.13. 5-((Z)-Methylbenzylidene)-2-((2-(E)-D-glueose)hydrazono)-4-imidazolidinone(12b): Yield 2.27 g (60%), red crystals, mp 210-212 °C; IR: v 3434 em~ (OH), 3190 em~ (Nil), 1718 cm"t (CO); ~H NMR: fi 2.30 (s, 1H,

Me), 3.35-3.70 (m, 4H, 6'-H, 6"-H, 5'-H, 4'-H), 3.80 (t, IH, J = 7.80 Hz, 6'-OH), 4.30 (m, 2H, 5'-OH, 4'OH), 4.55 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.70 (d, 1H, J = 6.21 Hz, T-OH), 6.35 (s, 1H, HC=C), 7.05 (d, 1H, J = 5.90 Hz, I'-H), 7.55 (d, 2H, Ar-H), 7.75 (d, 2H, At-H), 11.05 (hr. s, 1H, N~-H), 11.50 (s, 1H, N3-H); MS, m/z = 378 (bf'); Anal. Calcd. for CI7H22N406(378.38): C, 53.95; H, 5.86; N, 14.81. Found: C, 54.52; H, 5.84; N, 15.13. 5-((Z)-Methoxybenzylidene)-2-((2-(E)-D-glucose)hydrazono)-4-imidazolidinone (12c):

Yield 1.90 g

(48%), red crystals, nap 168-170 °C; IR: v 3430 cml (OH), 3194 cm"l (NH), 1720 cm"j (CO); IH NMR: 6 3.25-3.45 (ra, 2H, 6'-H, 6"-H), 3.65 (m, 2H, 5'-H, 4'-H), 3.75 (m, 4H, OMe, 6'-OH), 4.25 (m, 2H, 5'-OH, 4'OH), 4.50 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.75 (d, IH, J = 7.60 Hz, T-OH), 6.35 (s, 1H, HC=C), 7.05 (d, 1H, J = 7.10 Hz, I'-H), 7.55 (d, 2H, Ar-H), 7.75 (d, 2H, At-H), 11.05 (hr. s, 1H, N:H), 11.50 (s, 1H, N3-H); MS, m/z = 394 (M+); Anal. Calcd. for CI7H22N407(394.38): C, 51.79; H, 5.62; N, 14.21. Found: C, 52.00; H, 5.54; N, 14.08. 5-((Z)-Chlorobenzylidene)-2-((2-(E)-D-glueose)hydrazono)-4-imidazolidinone(12d): Yield 2.00 g (50%), red crystals, rrqa 197-199 °C; IR: v 3438 (OH), 3192 (NH), 1725 cm"~(CO); ~H-NMR: 6 3.30-3.45 (m, 2H, 6'H, 6"-H), 3.60 (m, 2H, 5'-H, 4'-H), 3.75 (t, 4H, J = 6.10 Hz, 6'-OH), 4.25 (m, 2H, 5'-OH, 4'-OH), 4.45 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.70 (d, 1H, J = 5.93 Hz, T-OH), 6.35 (s, IH, HC=C), 7.35 (d, IH, J = 6.20 Hz, I'H), 7.60 (d, 2H, Ar-H), 7.85 (d, 2H, Ar-H), 11.20 (hr. s, IH, NI-H), 11.75 (s, 1H, N3-H); MS, m/z = 399

4869

A. 1. Khodair, P. Bertrand/Tetrahedron 54 (1998)4859-4872

(M+); Anal. Calcd. for CI6HIgCIN406(398.80): C, 48.18; H, 4.80; N, 14.05. Found: C, 48.20; H, 4.85; N, 13.80.

5-((Z)-Benzylidene)-2-((2-(E)-D-mannose)hydrazono)-4-imidazolidinone

(13a): Yield 3.1)0 g (82%),

yellow crystals, mp 184-186 °C; IR: v 3433 crn~ (OH), 3200 cm"~ (NH), 1719 cm~ (CO); ~H NMR: 8 3.253.45 (rn, 2H, 6'-H, 6"-H), 3.50-3.70 (rn, 3H, 5'-H, 4'-H, 6'-OH), 4.25 (d, 1H, or = 6.00 Hz, 5'-OH), 4.35 (d, 1H, J = 6.32 Hz, 4'-OH), 4.45 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.83 (d, 1H, J = 5.95 Hz, 2'-OH), 6.35 (s, 1H, HC=C), 7.15 (d, 1H, J = 6.38 Hz, I'-H), 7.35-7.70 (m, 5H, Ar-H), 11.10 (br. s, IH, N~-H), 11.75 (s, 1H, N3H); MS, m/z = 364 (NC); Anal. Calcd. for Ct6H20N406 (364.36): C, 52.74; H, 5.53; N, 15.38. Found: C, 52.66; H, 5.78; N, 15.19. 5-((Z)-Methylbenzylidene)-2-((2-(E)-D-mannose)hydrazono)-4-imidazolidinone (13b):

Yield 2.91 g

(77%), yellow crystals, mp 198-200 °C; IR: v 3430 cm1 (OH), 3198 cm~ (NH), 1728 cm~ (CO); ~H NMR: 8 2.30 (s, IH, Me), 3.35-3.50 (m, 2H, 6'-H, 6"-H), 3.55-3.70 ((m, 3H, 5'-H, 4'-H, 6'-OH, 4.25 (d, 1H, 5'-OH, J =6.15 Hz), 4.35 (d, IH, or= 6.25 Hz, 4'-OH), 4.45 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.80 (d, 1H, or= 5.90 Hz, 2'OH), 6.33 (s, 1H, HC=C), 7.17 (d, 1H, J = 6.35 Hz, I'-H), 7.60 (d, 2H, Ar-H), 7.80 (d, 2H, At-H), 11.25 (br. s, 1H, N~-H), 11.75 (s, 1H, N3-H); MS, m/z = 378 (M+); Anal. Calcd. for CITH22N406(378.38): C, 53.95; H, 5.86; N, 14.81. Found: C, 53.70; H, 5.98; N, 14.95. 5-((Z)-Methoxybenzylidene)-2-((2-(E)-D-mannose)hydrazono)-4-imidazolidinone (13c): Yield 2.84 g (72%), yellow crystals, mp 188-190 °C; IR: v 3435 crn~ (OH), 3192 cm-~ (NH), 1727 cm~ (CO); ~H NMR: 8 3.25-3.50 (m, 2H, 6'-H, 6"-H), 3.58 (m, 2H, 5'-H, 4'-H), 3.75 (m, 4H, OMe, 6'-OH), 4.25 (d, 1H, J = 6.12 Hz, 5'-OH), 4.35 (d, 1H, J = 6.20 Hz, 4'-OH), 4.45 (m, 3H, 2'-H, 3'-H, 3'-OH), 4.75 (d, IH, or = 6.00 Hz, 2'OH), 6.35 (s, 1H, HC--C), 7.15 (d, 1H, or = 6.32 Hz, I'-H), 7.65 (d, 2H, Ar-H), 7.85 (d, 2H, Ar-H), 11.20 (br. s, 1H, N~-H), 11.75 (s, 1H, N3-H); MS, m/z = 394 (M+); Anal. Calcd. for C17H22N407 (394.38): C, 51.79; H, 5.62; N, 14.21. Found: C, 51.58; H, 5.67; N, 14.30. 5-((Z)-Chlorobenzylidene)-2-((2-(E)-D-mannose)hydrazono)-4-imidazolidinone (13d):

Yield 2.80

g

(70%), yellow crystals, mp 195-197 °C; IR: v 3436 cm~ (OH), 3194 cm~ (NH), 1720 crn~ (CO); ~H NMR: 8 3.25-3.50 (m, 2H, 6'-H, 6"-H), 3.60 (m, 3H, 5'-H, 4'-H, 6'-OH), 4.15 (d, 1H, J = 6.06 Hz, 5'-OH), 4.35 (d, IH, J = 6.10 Hz, 4'-OH), 4.45 (rm 3H, 2'-H, 3'-H, 3'-OH), 4.95 (d, 1H, ,/= 6.18 Hz, 2'-OH), 6.35 (s, 1H, HC=C), 7.42 (d, 1H, J = 6.30 Hz, I'-H), 7.70 (d, 2H, Ar-H), 7.86 (d, 2H, Ar-H), 11.30 (br. s, 1H, N~-H), 11.80 (s, 1H, N3-H); MS, m/z = 399 (M+); Anal. Calcd. for CI6H19CIN406(398.80): C, 48.18; H, 4.80; N, 14.05. Found: C, 48.32; H, 5.16; N, 13.75. 5-((Z)-Benzylidene)-2-((2-(E)-L-arabinose)hydrazono)-4-imidazolidinone (14a): Yield 2.52 g (75%), yellow crystals, mp 200-202 °C; IR: v 3430 cm"~ (OH), 3191 cm~ (NH), 1723 em1 (CO); tH NMR: 8 3.303.65 (m, 4H, 5'-H, 5"-H, 4'-H, 5'-OH), 4.45 (m, 2H, 2'-H, 3'-H), 4.50-4.80 (m, 3H, 2'-OH, 3'-OH, 4'-OH), 6.35 (s, IH, HC=C), 7.25 (d, 1H, J = 7.18 Hz, I'-H), 7.30-7.85 (ra, 5H, Ar-H), 11.20 (br. s, 1H, Nt-H), 11.60

4870

A. !. Khodair, P. Bertrand/Tetrahedron 54 (1998) 4859--4872

(s, 1H, NrH); MS, m/z = 334 (M+); Anal. Calcd. for C~5HtsN405 (334.33): C, 53.88; H, 5.42; N, 16.76. Found: C, 53.71; H, 5.48; N, 16.83. 5-((Z)-Methylbenzylidene)-2-((2-(E)-L-arabiaose)hydrazono)-4-imidazolidinone (14b): Yield 2.50 g (72%), yellow crystals, mp 196-198 °C; MS, m/z = 348 (M+); IR: v 3434 (OH), 3198 (N/I), 1726 cm"~ (CO);

~HNMR: 8 = 2.30 (s, 1H, Me), 3.35-3.65 (m, 4H, 5'-H, 5"-H, 4'-H, 5'-OH), 4.45 (m, 2H, 2'-H, 3'-H), 4.60 (m, 2H, T-OH, 4'-OH), 4.82 (d, 1H, J = 6.40 Hz, 2'-OH), 6.30 (s, 1H, HC=C), 7.16 (d, IH J = 6.60 Hz, l'H,), 7.60 (d, 2H, At-H), 7.70 (d, 2H, At-H), 10.95 (br. s, 1H, N~-H), 11.55 (s, 1H, N3-H); Anal. Calcd. for C~6H20N405(348.36): C, 55.16; H, 5.79; N, 16.08. Found: C, 54.86; H, 5.92; N, 15.98. 5-((Z)-Methoxybenzylidene)-2-((2-(E)-L-arabinose)hydrazono)-4-imidazolidinone (14c): Yield 2.53 g (69%), yellow crystals, mp 192-194 °C; IR: v 3430 em"t (OH), 3196 cm"l (NH), 1725 em"t (CO); ~H NMR: 6 3.30-3.65 (m, 3H, 5'-H, 5"-H, 4'-H), 3.75 (m, 4H, OMe, 5'-OH), 4.40 (m, 2H, 2'-H, 3'-H), 4.55 (d, 1H, J = 5.50 Hz, 4'-OH), 4.60 (d, 1H, J = 5.70 Hz, T-OH), 4.75 (d, 1H, J = 6.60 Hz, T-OH), 6.36 (s, IH, HC=C), 6.95 (d, 1H, J = 6.20 Hz, 1'-H),7.55 (d, 2H, Ar-H), 7.75 (d, 2H, At-H), 11.00 (hr. s, 1H, NrH), 11.52 (s, 1H, N3-H); MS, m/z = 364 (IVI~);Anal. Calcd. for Ct6H20N406 (364.36): C, 52.62; H, 5.53; N, 15.38. Found: C, 52.62; H, 5.57; N, 15.29. 5-((Z)-Chiorobenzylidene)-2-((2-(E)-L-arabinose)hydrazono)-4-imidazolidinone (14d): Yield 2.38 g (64%), yellow crystals, mp 197-199 °C; IR: v 3435 cmj (OH), 3200 em~ (NH), 1724 cm"~ (CO); ~H NMR: 8 3.35-3.60 (m, 3H, 5'-H, 5"-H, 4'-H), 3.75 (t, 1H, J = 9.50 Hz, 5'-OH), 4.42 (m, 2H, 2'-H, 3'-H), 4.55 (d, 1H, 4'-OH, J = 7.16 Hz), 4.60 (d, 1H, J = 6.00 Hz, 3'-OH), 4.70 (d, 1H, J = 6.60 Hz, T-OH), 6.30 (s, 1H, HC--C), 7.00 (d, 1H, J = 6.60 Hz, I'-H), 7.65 (d, 2H, At-H), 7.76 (d, 2H, At-H), 11.25 (br. s, IH, NrH), 11.74 (s, 1H, N3-H); MS, m/z = 369 (M+); Anal. Calcd. for CIsH17ClN405(368.78): C, 48.85; H, 4.65; N, 15.19. Found: C, 48.69; H, 4.88; N, 15.06. 5-((Z)-Benzylidene)-2-((2-(E)-D-xylose)hydrazono)-4-imidazolidinone(15a): Yield 2.42 g (72%), yellow crystals, mp 185-187 °C; IR: v 3437 cm"t (OH), 3192 em"j (NH), 1723 cm"t (CO); tH NMR: 8 3.30-3.60 (m, 4H, 5'-H, 5"-H, 4'-H, 5'-OH), 4.25 (rn, 2H, 2'-H), 4.35-4.65 (m, 3H, 3'-H, T-OH, 4'-OH), 4.95 (d, 1H, J = 6.00 Hz, 2'-OH), 6.35 (s, IH, HC=C), 7.20 (d, 1H, J = 6.20 Hz, I'-H), 7.35-7.85 (m, 5H, Ar-H), 10.95 (hr. s, 1H, NrH), 11.60 (s, 1H, N3-H); 13C NMR: 6 63.97 (C-5'), 70.59 (C-4'), 71.41 (C-2'), 72.86 (C-3'), 109.65 (=CH), 125.89 (C-5), 128.13, 129.16, 129.89, 134.78 (C-Ar), 154.96 (C-2), 156.18 (C-I'), 167.63 (C-4); MS, m/z = 334 (M*); Anal. Caled. for C15HtsN405(334.33): C, 53.88; H, 5.42; N, 16.76. Found: C, 54.13; H, 5.45; N, 16.57. 5-((Z)-Methylbenzylidene)-2-((2-(E)-D-xylose)hydrazono)-4-imidazolidinone(15b): Yield 2.55 g (73%), yellow crystals, mp 211-213 °C; IR: v 3433 cmt (OH), 3195 em~ (NH), 1720 cm"~ (CO); ~H NMR: 8 2.30 (s, IH, Me), 3.35-3.65 (m, 4H, 5'-H, 5"-H, 4'-H, 5'-OH), 4.20 (m, 2H, 2'-H), 4.35-4.60 (m, 3H, 3'-H, T-OH, 4'-OH), 4.97 (d, 1H, J = 6.50 I-Iz, T-OH), 6.30 (s, 1H, HC=C), 7.18 (d, 1H, J = 6.30 Hz, I'-H), 7.60 (d, 2H,

A. !. Khodair, P. Bertrand/Tetrahedron 54 (1998)4859-4872

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Ar-H), 7.70 (d, 2H, Ar-I-I), 10.90 (br. s, 1H, NI-H), 11.55 (s, 1H, N3-H); MS, m/z = 348 (IV[+);Anal. Caled. for Cj6H20N405 (348.36): C, 55.16; H, 5.79; N, 16.08. Found: C, 55.03; H, 6.13; N, 15.83. 5-((2)-Methoxybenzylidene)-2-((2-(E)-D-xylose)hydrazono)-4-imidazolidinone(15e): Yield 2.63 g (72%), yellow crystals, mp 198-200 °C; IR: v 3430 cm~ (OH), 3196 em~ (NH), 1725 em"~ (CO); JH NMR: 8 3.303.65 (m, 3H, 5'-H, 5"-H, 4'-H), 3.77 (m, 4H, OMe, 5'-OH), 4.25 (d, 2H, J = 6.10 Hz, 2'-H), 4.45 (d, IH, J = 4.80 Hz, 3'-H), 4.80 (m, 2H, 4'-OH, 3'-OH), 5.00 (d, 1H, J = 5.70 Hz, 2'-OH), 6.36 (s, 1H, HC=C), 6.95 (d, 1H, J = 6.60 Hz, 1'-H), 7.15 (d, 2H, Ar-H), 7.75 (d, 2H, At-H), 11.05 (br. s, 1H, N I-H), 11.50 (s, 1H, N3-H); MS, m/z -- 364 (M+); Anal. Calcd. for Ci6H20N406 (364.36): C, 52.62; H, 5.53; N, 15.38. Found: C, 53.01; H, 5.45; N, 15.22. 5-((Z)-Chlorobenzylidene)-2-((2-(E)-D-xylose)hydrazono)-4-imidazolidinone(15d): Yield 2.50 g (68%), yellow crystals, mp 192-194 °C; IR: v 3430 cmt (OH), 3197 cm"l (NH), 1725 cmt (CO); 1H-NMR: 8 3.353.60 (m, 3H, 5'-H, 5"-H, 4'-H), 3.75 (t, 1H, J = 8.80 Hz, 5'-OH), 4.30 (m, 2H, 2'-H), 4.45 (d, 1H, J = 5.5 Hz, 3'-H), 4.60 (m, 2H, 4'-OH, T-OH), 5.05 (d, 1H, J = 6.50 Hz, T-OH), 6.30 (s, 1H, HC=C), 7.00 (d, 1H, J = 6.50 Hz, I'-H), 7.65 (d, 2H, Ar-H), 7.75 (d, 2H, Ar-H), 11.20 (hr. s, 1H, Nt-H), 11.75 (s, 1H, N3-H); MS, m/z = 369 (M+); Anal. Calcd. for CtsHtTCIN405 (368.78): C, 48.85; H, 4.65; N, 15.19. Found: C, 48.91; H, 4.84; N, 14.86. Acknowledgment: We thank Prof. Jean-Pierre Gesson from University of Poitiers, Faculty of Sciences, for reviewing the manuscript, Dr. John P. Bader, Chief Antiviral Evaluation Branch and Dr. V. L. Narayanan, Chief Drug Synthesis and Chemistry Branch, National Cancer Institute, USA for carting out the antiviral testing and antitumor testing of the prepared compounds.

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