Synthesis of double headed imidazoline acyclo C-nucleosides: 1,4-bis[1-amino-5-oxo-4-substituted(imidazolin-2-yl)]galacto-tetritols

Article abstract of DOI:10.1081/NCN-120021433

Condensation of 2,3,4,5-tetra-O-acetyl-galactaroyl dichloride (1) with two equivalents of the α-amino esters 2a-c gave the corresponding 2,3,4,5-tetra-O-acetyl-galactaric acid diamides 3a-c. Heterocyclization of 3a-c by heating with hydrazine hydrate took place with concomitant de-O-acetylation of the polyacetoxyalkyl chain to give 1,4-bis[1-amino-5-oxo-4-substituted(imidazolin-2-yl)] galacto-tetritols (5a-c) and not the theoretically possible 1,2,4-triazinones 4 as indicated by spectral data. Compounds 5a-c readily reacted with p-nitrobenzaldehyde to give the corresponding p-nitrobenzylideneamino derivatives 6a-c. Acetylation of 5a-c afforded the 2,3,4,5-tetra-O-acetyl-1,4-bis[1-acetamido-5-oxo-4-substituted (imidazolin-2-yl)]galacto-tetritols (7a,b,d). De-O-acetylation of 7a,b,d gave 1,4-bis[1-acetamido-5-oxo-4-substituted (imidazolin-2-yl)]galactotetritols (8a-c).

Full text of DOI:10.1081/NCN-120021433

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Synthesis of Double Headed Imidazoline Acyclo C-
Nucleosides: 1,4-bis[1-Amino-5-oxo-4-Substituted-
(Imidazolin-2-yl)]galacto-tetritols
Adel Z. Nasr a b
a Department of Chemistry , Faculty of Science , Cairo University , Faiyoum, Egypt
b Department of Chemistry , Faculty of Science , Cairo University , Faiyoum, 63514, Egypt
Published online: 07 Feb 2007.
To cite this article: Adel Z. Nasr (2003) Synthesis of Double Headed Imidazoline Acyclo C-Nucleosides: 1,4-bis[1-Amino-5-
oxo-4-Substituted-(Imidazolin-2-yl)]galacto-tetritols, Nucleosides, Nucleotides and Nucleic Acids, 22:3, 349-357, DOI:
10.1081/NCN-120021433
To link to this article: http://dx.doi.org/10.1081/NCN-120021433
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 3, pp. 349–357, 2003
Synthesis of Double Headed Imidazoline Acyclo
C-Nucleosides: 1,4-bis[1-Amino-5-oxo-4-Substituted-
(Imidazolin-2-yl)]galacto-tetritols
*
Adel Z. Nasr
Department of Chemistry, Faculty of Science, Cairo University,
Faiyoum, Egypt
ABSTRACT
Condensation of 2,3,4,5-tetra-O-acetyl-galactaroyl dichloride (1) with two
equivalents of the a-amino esters 2a–c gave the corresponding 2,3,4,5-tetra-O-
acetyl-galactaric acid diamides 3a–c. Heterocyclization of 3a–c by heating with
hydrazine hydrate took place with concomitant de-O-acetylation of the poly-
acetoxyalkyl chain to give 1,4-bis[1-amino-5-oxo-4-substituted(imidazolin-2-yl)]
galacto-tetritols (5a–c) and not the theoretically possible 1,2,4-triazinones 4 as
indicated by spectral data. Compounds 5a–c readily reacted with p-nitrobenz-
aldehyde to give the corresponding p-nitrobenzylideneamino derivatives 6a-c.
Acetylation of 5a–c afforded the 2,3,4,5-tetra-O-acetyl-1,4-bis[1-acetamido-5-
oxo-4-substituted(imidazolin-2-yl)]galacto-tetritols (7a,b,d). De-O-acetylation of
7a,b,d gave 1,4-bis[1-acetamido-5-oxo-4-substituted (imidazolin-2-yl)]galacto-
tetritols (8a–c).
*Correspondence: Adel Z. Nasr, Department of Chemistry, Faculty of Science, Cairo Univer-
sity, Faiyoum 63514, Egypt; E-mail: Adelnasr@hotmail.com.
349
DOI: 10.1081/NCN-120021433
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

350
Nasr
INTRODUCTION
Imidazole acyclo C-nucleosides constitute an important class of acyclo C-
nucleosides[1–6] especially after the isolation and characterization of the naturally
occurring imidazole acyclo C-nucleoside antibiotic CV-1 [5-hydroxy-(D-arabino-
tetritol-1-yl)imidazolidin-2-one] from a strain of Streptomyces sp.II.[7] Accordingly,
considerable efforts have been directed toward the synthesis of many imidazole
acyclo C-nucleosides seeking their diverse biological activities.[1–6] Members of
imidazole acyclo C-nucleosides were found to produce lymphopenia,[8] depress blood
lymphocyte counts in both mice and rats,[9] prevent spontaneous and cyclophos-
phamide-induced diabetes in non-obese diabetic mice[10] as well as possess protein
kinase inhibition.[11] Moreover, multitudinous pharmaceutical activities[12–18] and
agrochemical applications[19–21] were attributed to compounds comprising imidazole
rings. These aspects prompted us to investigate a novel approach for the synthesis of
the title double headed imidazoline acyclo C-nucleosides as a part of a program
directed towards the synthesis of acyclo C-nucleosides.[22–25]
RESULTS AND DISCUSSION
Condensation of one molar equivalent of 2,3,4,5-tetra-O-acetyl-galactaroyl
dichloride (1)[26] with two molar equivalents of three a-amino esters, namely: glycine
ethyl ester (2a), L-phenylalanine methyl ester (2b) and L-tyrosine methyl ester (2c)
hydrochlorides gave products which showed three IR absorptions characteristic of
NH, ester and amide corbonyls. The products correctly analysed for the 2,3,4,5-
1
tetra-O-acetyl-galactaric acid diamide structures 3a–c. Each product exhibited H
NMR signals of two exchangeable NH protons, four tetritolyl chain protons and
four O-acetyl group protons. Compound 3a showed in addition, two ethyl group
protons and two methylene protons while compounds 3b and 3c showed the
expected two benzyl group protons, two CH protons and two methyl group protons
(compound 3c showed also two broad exchangeable OH protons).
Subjecting compound 3a to heterocyclization by heating with hydrazine hydrate,
gave a single crystalline product which revealed IR absorptions at 3310 (OH and
NH), 1663 (CON) and 1618 cmꢀ1 (C¼N) and lacked the ester carbonyl absorptions
of the parent 3a. The cyclization product correctly analysed for the molecular for-
mula C10H16N6O6 indicating that heterocyclization took place with concomitant
hydrazinolytic de-O-acetylation of the sugar chain. Accordingly, it may possess
the 1,4-bis[2,5-dihydro-6-oxo-1H-(1,2,4-triazin-3-yl)]galacto-tetritol (4) or the 1,4-
bis[1-amino-5-oxo-(imidazolin-2-yl)]galacto-tetritol (5a) structure. However the pro-
duct was assigned the imidazolinone structure 5a rather than the 1,2,4-triazinone
structure 4 on the bases of the following evidence. First, the appearance of the
two amino groups of 5a as one singlet signal at d 8.61. Had structure 4 been
obtained, two separate NH proton signals would have appeared as double one-
proton signals at d 10–11.5 and d 6.9–7.5 ppm.[27–29] Second, the ease of conden-
sation of the amino group of 5a with p-nitrobenzaldehyde to afford the correspond-
ing p-nitrobenzylideneamino derivative 6a. The alternative 1,2,4-triazinone structure
4 would not undergo such a reaction.

Double Headed Imidazoline Acyclo C-Nucleosides
351
Similarly, the diamides 3b,c were heterocyclized by heating with hydrazine
hydrate to the corresponding double headed acyclo C-nucleosides 5b,c. The mass
spectrum of 5b did not show its molecular ion peak, yet revealed peaks for the
alditolyl chain C1–C2 cleavage. The spectrum showed a fragment at m=z 217
corresponding to the heterocyclic base carrying a protonated formyl group
characterising C-nucleoside structures.[30] Condensation of compounds 5b or 5c
with p-nitrobenzaldehyde afforded the corresponding p-nitro-benzylideneamino
derivatives 6b and 6c.
Treatment of 5a–c with acetic anhydride in the presence of pyridine at room
temperature caused acetylation of the hydroxy groups as well as the imidazoline
amino group to give the 2,3,4,5-tetra-O-acetyl-1,4-bis[1-acetamido-5-oxo-4-substi-
tuted(imidazolin-2-yl)]galacto-tetritols 7a,b,d. IR spectra of the latter compounds
1
showed OAc, CON and C¼N absorptions. The H NMR spectra of the prepared
compounds showed two exchangeable NH protons, four tetritolyl chain protons,
two acetamido methyl protons and four acetoxy methyl protons (compound 7d
showed two additional aryloxy acetyl group protons), in addition compound 7a
showed two imidazolinyl CH2 protons while compounds 7b and 7d showed the
expected two benzyl group protons and two imidazolinyl CH protons. The mass
spectrum of 7b showed the characteristic protonated formyl heterocylic fragment
at m=z 260.
De-O-acetylation of 7a,b,d with a solution of ammonium hydroxide and metha-
nol gave the corresponding 1,4-bis[1-acetamido-5-oxo-4-substituted (imidazolin-
2-yl)]galacto-tetritols 8a–c which showed (OH and NH), (CON) and (C¼N) IR
absorptions.
EXPERIMENTAL
Melting points were determined on MEL-TEMP II melting point apparatus in
open glass capillaries and are uncorrected. The infrared spectra IR were recorded
for potassium bromide discs on a Pye-Unicam SP1025 spectrophotometer. Proton
magnetic resonance 1H NMR spectra were carried out at ambient temperature
(ꢁ25ꢂC) with a Varian EM-390 or with a Brucker AC-250 spectrometers using tetra-
methylsilane (TMS) as an internal standard. Mass spectra (MS) were performed on a
Hewlett-Packard 5995 gas chromatography-mass spectrometer system. Homo-
geneity of the products and follow up of the reactions were checked by ascending
thin-layer chromatography TLC on plates precoated with silica gel G (E. Merck;
layer thickness 0.25 mm), used without pretreatment. All ratios of the used solvent
systems were volume to volume V=V, the solvent system used were: (A)
CHCl3=MeOH (9:1) and (B) CHCl3=MeOH (1:1); the distance of the solvent travel
was 5 cm and the spots were visualised by exposure to iodine vapour for a few min-
utes. Elemental microanalyses were performed at the Microanalytical Unit, Cairo
University, Cairo, Egypt.
General Procedure for the Preparation of 2,3,4,5-Tetra-O-acetyl-galactaric acid
diamides (3a–c). A solution of 1 (5 mmol) in dry benzene (30 mL) was gradually
added to a stirred solution of the appropriate a-amino ester hydrochloride

352
Nasr
(2a–c, 10 mmol) in dry pyridine (15 mL) at ambient temperature. After stirring for
3 h, the solvents were evaporated under reduced pressure and the syrupy residue
was crystallised from EtOH. The following compounds were prepared:
2,3,4,5-Tetra-O-acetyl-galactaric acid di(glycine ethyl ester)amide(3a). Color-
less crystals; Yield: 70%; m.p.: 198–200ꢂC; TLC: (A), Rf: 0.51; IR: 3244 (NH),
1755 (ester C¼O) and 1678 cmꢀ1 (CON); 1H NMR (CDCl3): d 9.61 (s, 2 H, exchange-
able, 2 NH), 6.26, 5.50 (2s, 2 H each, tetritoldi-1,4-yl 4 H), 4.78 (q, 4 H, 2 CH2CH3),
3.31 (s, 4 H, 2 CH2), 2.18, 2.15 (2 s, 6 H each, 4 OAc), 1.24 (t, 6 H, 2 CH2CH3).
Anal. Calcd. for C22H32N2O14: C, 48.2; H, 5.8; N, 5.1. Found: C, 48.3; H, 5.9;
N, 5.1.
2,3,4,5-Tetra-O-acetyl-galactaricaciddi(phenylalaninemethylester)amide(3b). Co-
lorless crystals; Yield: 78%; m.p.: 206–208ꢂC; TLC: (A), Rf: 0.53; IR: 3277 (NH),
1759 (ester C¼O) and 1665 cmꢀ1 (CON); 1H NMR (CD3): d 9.86 (s, 2 H, exchange-
able, 2 NH), 7.66–7.14 (m, 10 H, ArH), 5.65, 5.37 (2 s, 2 H each, tetritoldi-1,4 yl 4H),
5.06–4.81 (m, 2 H, CONHCH). 4.16–3.98 (m, 4 H, 2 benzyl CH2), 3.75 (s, 6 H, 2
OCH3), 2.28, 2.19 (2 s, 6H, 4 OAc).
Anal. Calcd. for C34H40N2O14: C, 58.3; H, 5.7; N, 4.0. Found: C, 58.4; H, 5.6;
N, 4.0.
2,3,4,5-Tetra-O-acetyl-galactaric acid di(Tyrosine methyl ester)amide (3c). Color-
less crystals; Yield: 75%; m.p.: 220–222ꢂC. TLC: (A), Rf: 0.49; IR: 3430 (OH),
3319 (NH). 1764 (ester C¼O), and 1676 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]: d
9.93 (s, 2 H, exchangeable, 2 NH), 7.23–6.85 (m, 8 H, ArH), 5.85, 5.45 (2 d, 2 H each,
tetritoldi-1,4-yl, 5.16–4.99, (m, 2 H, CONHCH), 4.46 (s, broad, 2 H, exchangeable, 2
OH) 4.11–3.92 (m, 4 H, 2 benzy CH2), 3.74 (s, 6 H, 2OCH3), 2.28, 2.09 (2 s, 6 H, 4
OAc).
Anal. Calcd. for C34H40N2O16: C, 55.7; H, 5.5; N, 3.8. Found: C, 55.7; H, 5.4;
N, 3.9.
General Procedure for the Preparation of 1,4-Bis(1-amino-5-oxo-4-substituted
(imidazolin-2-yl)]galacto-tetritols (5a–c). A mixture of the particular diamide (3a–c,
1 mmol) and hydrazine hydrate (50 mL) was heated at reflux for 4 h and then eva-
porated under reduced pressure. The obtained residue was crystallized from a
H2O=MeOH-mixture. The following compounds were prepared:
1,4-Bis[1-amino-5-oxo-(imidazolin-2-yl)]galacto-tetritol(5a). Colorless crystals;
Yield: 61%; m.p.: 266–270ꢂC=dec.; TLC: (B), Rf: 0.52; IR: 3310 (broad, OH þ NH),
1663 (CON), and 1618 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]: d 8.61 (s, 4 H, exchange-
able, 2 NH2), 5.10, 4.40 (2 s, broad, exchangeable, 2 OH each), 4.18, 3.76 (2 d, 2 H
each, tetritoldi-1,4-yl 4 H), 3.29 (s, 4 H, 2 imidazolinyl CH2).
Anal. Calcd. for C10H16N6O6: C, 38.0; H, 5.1; N, 26.6. Found: C, 38.2; H, 5.0;
N, 26.5.
1,4-Bis[1-amino-4-benzyl-5-oxo-(imidazolin-2-yl)]galacto-tetritol (5b). Colorless
crystals; Yield: 67%; m.p.: 238–240ꢂC=dec.; TLC: (B), Rf: 0.49; IR: 3376, 3320

Double Headed Imidazoline Acyclo C-Nucleosides
353
(OH), 3182 (NH), 1661 (CON), and 1604 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]: d 8.79
(s, 4 H, exchangeable, 2 NH2), 7.91–6.61 (m, 12 H, 10 ArH, 2 imidazolinyl H), 5.71,
5.39 (2 d, exchangeable, 2 OH each), 4.97, 4.61 (2 s, 2 H each, tetritoldi-1,4-yl 4 H),
4.52 (s, 4 H, 2 benzyl CH2).
Anal. Calcd. for C24H28N6O6: C, 58.1; H, 5.7; N, 16.9. Found: C, 58.2; H, 5.7;
N, 16.9.
1,4-Bis[1-amino-4-(p-hydroxybenzyl)-5-oxo-(imidazolin-2-yl)]galacto-tetritol
(5c). Colorless crystals; Yield: 63%; m.p.: 300–304ꢂC=dec; TLC: (B), Rf: 0.47; IR:
3327 (broad, OH þ NH), 1665 (CON), and 1618 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]:
d 8.81 (s, 4 H, exchangeable, 2 NH2), 7.84–6.53 (m, 10 H, 8 ArH, 2 imidazolinyl H),
5.51, 5.23 (2 d, exchangeable, 2 OH each), 4.99 (s, board, 2 H, exchangeable 2 OH),
4.81, 4.69 (2 s, 2 H each, tetritold 1,4-yl 4 H), 4.41 (s, 4 H, 2benzyl CH2).
Anal. Calcd. for C24H28N6O8: C, 54.5; H, 5.3; N, 15.9. Found: C, 54.6; H, 5.2;
N, 15.8.
General Procedure for the Preparation of p-Nitrobenzylideneamino derivatives(6a–c).
A solution of the particular 5a–c (0.5 mmol) in H2O (15 mL) was treated with a solution
of p-nitrobenzaldehyde (0.5 mmol) in ethanol (25 mL) and the mixture was heated
at 100ꢂC for 30 min. The product which separated after attaining ambient temperature
was filtered and crystallized from a H2O=MeOH – mixture. The following compounds
were prepared:
1,4-Bis[1-(p-nitrobenzylideneamino)-5-oxo-(imidazolin-2-yl)]galacto-tetritol(6a).
Pale yellow crystals; Yield: 72%; m.p.: 238–240ꢂC; TLC: (B), Rf: 0.50; IR: 3361
1
(broad, OH), 1681 (CON), 1645, and 1629 cmꢀ1 (C¼N); H NMR [(CD3)2SO]: d
8.20–7.81 (m, 10 H, 8 ArH, 2 CH¼N), 5.23, 4.64 (2 d, exchangeable 2 OH each),
4.59, 4.19 (2 d, 2 H each, tetritoldi-1,4-yl 4 H), 3.49 (s, 4 H, 2 imidazolinyl CH2).
Anal. Calcd. for C24H22N8O10: C, 49.5; H, 3.8; N, 19.2. Found: C, 49.5; H, 3.9;
N, 19.3.
1,4-Bis[1-(p-nitrobenzylideneamino)-4-benzyl-5-oxo-(imidazolin-2-yl)] galacto-
tetritol(6b). Pale yellow crystals; Yield: 68%; m.p. 226–228ꢂC=dec.; TLC: (B), Rf:
1
0.47; IR: 3393 (broad, OH), 1679 (CON), 1645, and 1627 cmꢀ1 (C¼N); H NMR
[(CD3)2SO]: d 8.37–7.82 (m, 18 H, ArH), 7.32–6.84 (m, 4 H, 2 CH¼N, 2 imidozolinyl
H), 5.74, 5.34 (2 d, exchangeable 2 OH each), 4.93, 4.54 (2 s, 2 H each, tetritoldi-1,4-yl
4 H), 4.31 (s, 4 H, 2 benzyl CH2).
Anal. Calcd. for C38H34N8O10: C, 59.8; H, 4.5; N, 14.7. Found: C, 59.9; H, 4.4;
N, 14.8.
1,4-Bis[1-(p-nitrobenzylideneamino)-4-(p-hydroxybenzyl)-5-oxo-(imidazolin-2-yl)]
galacto-tetritol (6c). Pale yellow crystals; Yield: 62%; m.p. 268–270ꢂC=dec.; TLC:
(B), Rf: 0.45; IR: 3329 (broad, OH), 1678 (CON), 1646, and 1628 cmꢀ1 (C¼N);
1H NMR [(CD3)2SO]: d 8.54–7.58 (m, 16 H, ArH), 7.21–6.90 (m, 4 H, 2 CH¼N,
2 imidazolinyl H), 5.67, 5.29 (2 d, exchangeable 2 OH each), 5.01 (s, broad, 2 H,
exchangeable, 2 OH), 4.88, 4.39 (2 s, 2 H each, tetritoldi-1,4-yl 4 H), 4.21 (s, 4 H,
2 benzyl CH2).

354
Nasr
Anal. Calcd. for C38H34N8O12: C, 57.4; H, 4.3; N, 14.1. Found: C, 57.4; H, 4.3;
N, 14.0.
General Procedure for the Preparation of 2,3,4,5-Tetra-O-acetyl-1,4-bis
[1-acetamido-5-oxo-4-substituted(imidazolin-2-yl)]galacto-tetritols (7a,b,d). A mix-
ture of the respective 5a–c (5 mmol) in pyridine (5 mL) and acetic anhydride
(25 mL) was stirred for 24 h at ambient temperature. The mixture was evaporated
under reduced pressure and the residue was crystallized from EtOH. The following
compounds were prepared:
2,3,4,5-Tetra-O-acetyl-1,4-bis[1-acetamido-5-oxo-(imidazolin-2-yl)] galacto-
tetritol (7a). Colorless crystals; Yield: 71%; m.p.: 260–261ꢂC=dec.; TLC: (A),
Rf: 0.55; IR: 3459 (NH), 1741 (OAc), 1662 (CON), and 1645 cmꢀ1 (C¼N); 1H NMR
(CDCl3): d 13.20 (s, 2 H, exchangeable, 2 NH), 6.47, 5.87 (2 s, 2 H each, tetrito-
ldi-1,4-yl-4 H), 3.33 (s, 4 H, 2 imidazolinyl CH2), 2.47 (s, 6 H, 2 NAc), 2.19, 2.09
(2 s, 6 H each, 4 OAc).
Anal. Calcd. for C22H28N6O12: C, 46.5; H, 4.9; N, 14.8. Found: C, 46.6; H, 4.8;
N, 14.7.
2,3,4,5-Tetra-O-acetyl-1,4-bis[1-acetamido-4-benzyl-5-oxo-(imidazolin-2-yl)]galacto-
tetritol (7b). Colorless crystals; Yield: 68%; m.p.: 250–251ꢂC=dec.; TLC: (A), Rf: 0.53;
1
IR: 3440 (OH), 1740 (OAc), 1675 (CON), and 1642cmꢀ1 (C¼N); H NMR (CDCl3):
d 13.09 (s, 2 H, exchangeable, 2 NH), 7.42–6.98 (m, 12 H, 10 ArH, 2 imidazolinyl H),
6.54, 5.73 (2 s, 2 H each, tetritoldi- 1,4-yl 4 H), 4.11 (d, 4 H, 2 benzyl CH2), 2.54 (s, 6
H, 2 NAC), 2.13, 2.01 (2 s, 5 H each, 4 OAc).
Anal. Calcd. for C36H40N6O12:C, 57.8; H, 5.4; N, 11.2. Found: C, 57.7; H, 5.4;
N, 11.1.
2,3,4,5-Tetra-O-acetyl-1,4-bis[1-acetamido-4-(p-acetoxybenzyl)-5-oxo-(imidazolin-
2-yl)]galacto-tetritol (7d). Colorless crystals; Yield: 65%; m.p.: 254–255ꢂC=dec.; TLC:
1
(A), Rf: 0.51; IR: 3460 (NH), 1741 (OAc), 1663 (CON), and 1644 cmꢀ1 (C¼N); H
NMR (CDCl3): d 13.31(s, 2 H, exchangeable, 2 NH), 7.62–7.27 (m, 10 H, 8 ArH, 2 imi-
dazolinyl H), 6.67, 5.65 (2 s, 2 H each, tetritoldi-1,4-yl 4 H), 4.40 (d, 4 H, 2 benzyl CH2),
2.20 (s, 6 H, 2NAc), 2.11, 2.08, 2.04 (3 s, 6 H each, 6 OAc).
Anal. Calcd. for C40H44N6O10: C, 55.6; H, 5.1; N, 9.7. Found: C, 55.7; H, 5.0;
N, 9.8.
General Procedure for the Preparation of 1,4-Bis[1-acetamido-5-oxo-4-substi-
tuted-(imidazolin-2-yl)]galacto-tetritols (8a–c).
A solution of the appropriate
7a,b,d (2 mmol) in methanol (50 mL) was treated with 20% aqueous NH3 solution
(15 mL) and kept at ambient temperature for 24 h. Evaporation of the solvent under
reduced pressure gave a residue which crystallized from a H2O=MeOH – mixture.
The Following compounds were prepared:
1,4-Bis[1-acetamido-5-oxo-(imidazolin-2-yl)]galacto-tetritol (8a). Colorless crys-
tals; Yield: 57%; m.p.: 328–330ꢂC=dec.; TLC: (B), Rf: 0.58; IR: 3439 (broad
OH þ NH), 1694 (CON) and 1645 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]: d 13.14

Double Headed Imidazoline Acyclo C-Nucleosides
355
(s, 2 H, exchangeable, 2 NH), 5.53, 4.91 (2 d, exchangeable, 2 OH each), 4.77, 3.80
(2 d, 2 H each, tetritoldi-1,4-yl 4 H), 3.53 (s, 4 H, 2 imidazolinyl CH2), 2.89 (s, 6 H,
2 NAc).
Anal. Calcd. for C14H20N6O8: C, 42.0; H, 5.0; N, 21.0. Found: C, 42.1; H, 5.0;
N, 21.1.
1,4-Bis[1-acetamido-4-benzyl-5-oxo-(imidazolin-2-yl)]galacto-tetritol(8b). Color-
less crystals; Yield: 61%; m.p.: >350ꢂC; TLC: (B), Rf: 0.56; IR: 3301 (broad OH þ NH),
1694 (CON), and 1600 cmꢀ1 (C¼N); 1H NMR [(CD3)2SO]: d 13.04 (s, 2 H, exchange-
able, 2 NH), 7.37–6.82 (m, 12 H, 10 ArH, 2 imidozolinyl H), 5.84, 5.17 (2 d, exchange-
able, 2 OH each), 4.83, 4.59 (2 s, 2 H each, tetritoldi-1,4-yl 4 H), 4.39 (s, 4 H, 2 benzyl
CH2), 2.94 (s, 6 H, 2 NAc).
Anal. Calcd. for C28H32N6O8: C, 57.9; H, 5.5; N, 14.5. Found: C, 57.9; H, 5.4;
N, 14.5.
1,4-Bis[1-acetamido-4-(p-hydroxybenzyl)-5-oxo-imidazolin-2-yl)galacto-tetritol
(8c). Colorless crystals; Yield: 64%; m.p.: > 350ꢂC; TLC: (B), 0.53; IR: 3442
1
(broad OH þ NH), 1685 (CON), and 1614 cmꢀ1 (C¼N); H NMR [(CD3)2SO]: d
13.21 (s, 2 H, exchangeable), 7.21–6.73 (m, 10 H, 8 ArH, 2 imidazolinyl H), 5.73,
5.22 (2 d, exchangeable, 2 OH each), 4.92 (s, broad, 2 H, exchangeable 2 OH),
4.71, 4.21 (2 s, 2 H each, tetritoldi-1,4-yl 4 H), 4.09 (s, 4 H, 2 benzyl CH2), 2.89
(s, 6 H, 2 NAc). Anal. Calcd. for C28H32N6O16: C, 54.9; H, 5.2; N, 13.7. Found:
C, 54.8; H, 5.2; N, 13.8.
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Received October 8, 2002
Accepted January 27, 2003