A mercapto analogue of 5′-noraristeromycin

Article abstract of DOI:10.1016/S0968-0896(01)00271-1

5′-Noraristeromycin (1) and its enantiomer (2) have been found to possess a wide range of antiviral effect. In the search for analogues of 1 and 2 with improved activity, the synthesis of both enantiomers of 5′-mercapto-5′-deoxy-5′noraristeromycin (Figure 1, Scheme 1 and Scheme 2 and 7) has been accomplished. While (+)-7 was inactive, (-)-Figure 1, Scheme 1 and Scheme 2 did show marginal activity against vaccinia virus, but not any other virus. Copyright

Full text of DOI:10.1016/S0968-0896(01)00271-1

Bioorganic & Medicinal Chemistry 10 (2002) 457–460
A Mercapto Analogue of 50-Noraristeromycin
Subha R. Das,a Stewart W. Schneller,a,* Jan Balzarinib and Erik De Clercqb
aDepartment of Chemistry, Auburn University, Auburn, AL 36849-5312, USA
bRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
Received 4 December 2000; accepted 23 August 2001
Abstract—50-Noraristeromycin (1) and its enantiomer (2) have been found to possess a wide range of antiviral effects. In the search
for analogues of 1 and 2 with improved activity, the synthesis of both enantiomers of 50-mercapto-50-deoxy-50-noraristeromycin (6
and 7) has been accomplished. While (+)-7 was inactive, (À)-6 did show marginal activity against vaccinia virus, but not any other
virus. # 2001 Elsevier Science Ltd. All rights reserved.
Introduction
the subsequent oxidation under glycolization condi-
Carbocyclic nucleosides and nucleotides have found a
meaningful niche in the ongoing search for new medic-
inal agents.1 Their success can be traced to their meta-
bolic stability and their substrate compatibility with
many enzymes relevant to nucleoside bio-conversions.2
Several years ago, we began3 a systematic study of car-
bocyclic nucleosides (carbanucleosides) lacking the 50-
methylene appendage (50-norcarbanucleosides). From
that effort, both enantiomers of the adenine system (1
and 2) were found to have significant biological prop-
erties.3b,4 In the search for compounds related to 1 and
2 that could improve upon their effectiveness, the amino
(3),5 epimeric (4),6,7 and fluoro (5)6 analogues and their
enantiomers8 were investigated. To continue the series
of varying the C-40 substituent, the mercapto derivatives
(6 and 7) have been prepared and their antiviral effects
evaluated (Fig. 1).
tions.11 In that regard, subjecting 9 to osmium tetroxide/
N-methylmorpholine N-oxide (NMO) dihydroxylation
provided the glycol 10. Basic conditions, expected to
deprotect 10 to yield the target 6, proved to be too
drastic, leading to decomposition. In an effort to avoid
these harsh conditions, attempts to prepare debenzoylated
9 were sought. However, its preparation via the palladium-
catalyzed coupling of potassium thioacetate with 8 lacking
the protecting benzoyl group was unsuccessful and no
other methods were attempted.
In seeking another approach to 6 (and 7), two variations
were considered: (i) having the 20,30-dihydroxyl groups
in place prior to sulfur introduction, and (ii) avoiding
the benzoyl protecting group. The chiral cyclopente-
none 1112 (Scheme 2) provided the essential features for
addressing i, and allowed for further elaboration to 6 by
the Michael reaction of a thio nucleophile to its C-3
Chemistry
In designing a reasonable approach to 6 (and, in turn, 7)
formation of the C–S bond at the 40-position was initi-
ally considered via the palladium catalyzed coupling of
the allylic acetate 85 with potassium thioacetate9
(Scheme 1). The resultant allylic thioacetate 9, availed
the sulfur in a deactivated form10 and protected it from
*Corresponding author. Tel.: +1-334-844-5737; fax: +1-334-844-
5748; e-mail: schnest@auburn.edu
Figure 1.
0968-0896/02/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved.
PII: S0968-0896(01)00271-1

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S. R. Das et al. / Bioorg. Med. Chem. 10 (2002) 457–460
Scheme 1. Reaction conditions. (a) KSAc, 5 mol% Pd(Ph3P)4, 15 mol% Ph3P, THF/DMSO (76%); (b) OsO4, NMO, THF/H2O (18%).
Scheme 2. Reaction conditions. (a) 4-methoxy-a-toluenethiol, K2CO3, THF (99%); (b) BH3.THF (60%); (c) DIAD, Ph3P, 6-chloropurine, THF;
(d) NH3, MeOH, 110 ꢀC (71% from steps c and d); (e) TFA, PhOH, reflux (75%).
atom and manipulation of its C-1 carbonyl center for
creating the linkage to the purine base (6-chloropurine).
their NMR spectral properties with compounds
prepared in an identical way.3c,12 The coupling of 6-
chloropurine to the alcohol 14, under Mitsunobu con-
ditions, followed by treatment with methanolic ammo-
nia produced 15. Deprotection of the isopropylidene
group as well as the removal of the p-methoxybenzyl
function9 of 15 was achieved in one step with
trifluoroacetic acid, to provide 6.
Thus, 4-methoxy-a-toluenethiol (p-methoxybenzyl-
mercaptan) was seen as a pro-thiol source and under-
went a Michael addition to the chiral cyclopentenone
1112 to furnish the product 13. Reduction of 13 with
borane-THF12 afforded the alcohol 14. The stereo-
chemistry of 13 and 14 was confirmed by correlating
By an analogous route, 7 was obtained from the
enantiomer of 11.12
Table 1. Activity of compounds 6 and 7 against different viruses
Cella
MIC50 (mg/mL)b
Antiviral results
Virus
Compounds 6 and 7 were evaluated against a wide
variety of viruses: herpes simplex virus type 1 (HSV-À1)
6
7
HSV-1 (KOS)
HSV-2(G)
HSV-1 TKÀ B2006
HSV-1 TKÀ VMW1837
VV
VSV
VSV
RSV
Coxsakie B4
Coxsakie B4
Parainfluenza-3
Reovirus-1
Sindbis
E6SM
E 6SM
E6SM
E6SM
E6SM
E6SM
HeLa
HeLa
HeLa
Vero
Vero
Vero
Vero
Vero
CEM
> 80
240
> 80
> 80
48
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 80
> 250
> 250
> 50
> 200
> 200
> 200
and type 2(HSV-2), thymidine kinase-deficient (TK
)
HSV-1, vaccinia virus (VV), vesicular stomatitis virus
(VSV), respiratory syncytial virus (RSV), cytomegalo-
virus (CMV), varicella-zoster virus (VZV), human
immunodeficiency virus type 1 (HIV-1) and type 2
(HIV-2), and others as indicated in Table 1. The only
virus affected was vaccinia virus, by compound 6, and
this only marginally. Since vaccinia virus is sensitive to
agents that inhibit S-adenosylhomocysteine (AdoHcy)
hydrolase, it is plasubile that 6 is acting in the same
manner, albeit with much less potency than 1, which is
an inhibitor of AdoHcy hydrolase.3 In addition to those
viruses listed in Table 1, neither compound 6 nor 7 was
active when assayed against hepatitis-B virus (HBV).
> 80
> 400
> 400
> 400
> 80
> 80
> 80
> 80
> 80
> 250
> 250
> 200
> 200
> 200
> 200
Punta toro
HIV-1
HIV-2CEM
CMV (AD-169)
CMV (Davis)
VZV (OKA)
VZV (YS)
HEL
HEL
HEL
HEL
aMinimum cyctotoxic concentration required to cause
a
micro-
Conclusions
scopically detectable alteration of normal E6SM, HeLa and Vero cell
morphology was ꢁ 400 mg/mL for 6 and > 400, >80 and ꢁ 80,
respectively, for 7; in HEL and CEM cells: > 200 and > 250, respec-
tively, for both 6 and 7.
The limited activity of compounds 6 and 7 suggests that
further efforts to improve upon the properties of com-
pound 1 and 2 are not likely to arise following a free 40-
thiol lead. Nevertheless, the activity of compound 6
bRequired to reduce virus-induced cytopathicity by 50%.

S. R. Das et al. / Bioorg. Med. Chem. 10 (2002) 457–460
459
towards vaccinia virus corroborates the notion that the
50-methylene unit of traditional carbocyclic nucleosides
is not a structural requirement for molecular recognition
and consequent antiviral activity.
red at room temperature for 5 days. Sodium bisulfite (1
g) was added to the reaction mixture and stirring
continued for 10 min. The contents of the flask were
then filtered, evaporated and the residue purified by
column chromatography. Elution with EtOAc/MeOH
(5:1) provided 10 (200 mg, 18%) as a white solid: mp
>60 ꢀC (dec.); H NMR (DMSO-d6) d 2.12 (m, 1H),
1
Experimental
Chemistry
2.37 (s, 3H), 2.73 (m, 1H), 3.70 (m, 1H), 3.95 (br, 1H),
4.51 (br, 1H), 4.87 (dd, 1H), 5.25 (d, 1H), 5.37 (d, 1H),
7.51-7.67 (m, 5H), 8.03 (d, 1H), 8.53 (s, 1H), 8.73 (s,
1H); 13C NMR (DMSO-d6) d 30.4, 32.4, 44.0, 59.3, 73.8,
74.9, 126.1, 128.4, 132.3, 133.4, 144.2, 150.2, 151.1,
152.4, 165.5, 195.2. Anal. calcd for C19H19N5O4S: C,
55.20; H, 4.63; N, 16.94; S, 7.75. Found: C, 54.98; H,
5.04; N, 16.71; S, 7.53.
Melting points were recorded on a Meltemp II melting
point apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded on a Bruker AC 250 spectrometer
(operated at 250 or 62.5 MHz, respectively). All 1H
chemical shifts are reported in d relative to internal
standard tetramethylsilane (TMS, d 0.00). 13C chemical
shifts are reported in d relative to CDCl3 (center of tri-
plet, d 77.23) or relative to DMSO-d6 (center of septet, d
39.51). The spin multiplicities are indicated by the sym-
bols s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet) and br (broad). Optical rotations were
determined using the sodium-D line on a JASCO DIP-
360 polarimeter. Elemental analyses were performed by
either M-H-W-Laboratories, Phoenix, Arizona, or
Atlantic Microlabs, Atlanta, Georgia. Reactions were
monitored by thin-layer chromatography (TLC) using
0.25 mm E. Merck silica gel 60-F254 precoated silica gel
plates with visualization by irradiation with a Minera-
light UVGL-25 lamp or exposure to iodine vapor. Col-
umn chromatography was performed on Whatman
silica gel (average particle size 5–25 mm, 60 A) and elu-
tion with the indicated solvent system. Yields refer to
chromatographically and spectroscopically (1H and 13C
NMR) homogeneous materials.
(2R,3S,4S)-4-S-(p-Methoxybenzyl)thio-2,3-(isopropylide-
nedioxy)-1-cyclo-pentanone (13). Potassium carbonate
(5.6 g, 40.6 mmol) was added to a solution of the
cyclopentenone 1112 (5 g, 32.5 mmol) in dry THF (150
mL), followed by 90% 4-methoxy-a-toluenethiol (6.3
mL, 40.6 mmol). The reaction mixture was stirred under
N2 at room temperature for 3 h, then filtered and eva-
porated to dryness. The residual oil was purified by
column chromatography (elution 8:1, hexane/EtOAc) to
afford 13 (9.9 g, 99%) as a white crystalline solid: mp.
120–122 ꢀC; H NMR (CDCl3) d 1.34 (s, 3H), 1.41 (s,
1
3H), 2.24 (d, 1H), 3.00 (q, 1H), 3.34 (d, 1H), 3.77 (s,
2H), 3.80 (s, 3H), 4.36 (d, 1H), 4.68 (d, 1H), 6.86 (d,
2H), 7.25 (d, 2H); 13C NMR (CDCl3) d 25.2, 27.0, 35.4,
39.7, 40.3, 55.5, 78.3, 81.5, 113.2, 114.4, 129.0, 130.2,
159.2, 211.5. Anal. calcd for C16H20O4S: C, 62.32; H,
6.54; S, 10.40. Found: C, 62.21; H, 6.59; S, 10.47.
(1S,2S,3S,4S)-4-S-(p-Methoxybenzyl)thio-2,3-(isopropy-
lidenedioxy)-cyclopentan-1-ol (14). To a solution of 13
(5 g, 16.2mmol) in dry THF (50 mL) cooled to À20 ꢀC
(10R,40S)-N-[9-(40-Acetylthio-20-cyclopentenyl)-9H-purin-
6-yl]-benzamide (9). A solution of the allylic acetate 85
(3 g, 8.26 mmol) in THF (80 mL) was stirred with tri-
phenylphosphine (Ph3P) (0.32g, 15 mol%) and
Pd(Ph3P)4 (0.5 g, 5 mol%) under N2 for 30 min. This
solution was then added dropwise to a stirred solution
of KSAc (1.88 g, 16.5 mmol) in THF/DMSO (1:1, 40
mL). After the addition was completed, the reaction
mixture was stirred at 55 ꢀC under N2 for 16 h. The
reaction mixture was then filtered, evaporated under
reduced pressure, extracted in CH2Cl2 and washed with
H2O. The organic layer was dried (Na2SO4), evaporated
and purified by column chromatography. Elution with
EtOAc/MeOH (25:1) provided 9 (2.4 g, 76%) as a yel-
.
was added 1.0 M BH3 THF complex (48.5 mL, 48.5
mmol) under N2. The reaction mixture was then stirred
at room temperature for 3 h, cooled in an ice bath and
the reaction quenched with H2O (10 mL) added drop-
wise. The reaction mixture was then evaporated,
extracted in CH2Cl2, washed with 10% NaOH (3 Â 50
mL), brine (2 Â 50 mL), dried (Na2SO4) and evapo-
rated. The residual oil was purified by column chroma-
tography (25:1, CH2Cl2/EtOAc) to furnish 14 (3.0 g,
1
60%) as a colorless oil: H NMR (CDCl3) d 1.34 (s,
3H), 1.47 (s, 3H), 1.72 (br, 1H), 1.96 (m, 2H), 2.37 (d,
1H), 3.03 (m, 1H), 3.65 (s, 2H), 3.79 (s, 3H), 4.22 (m,
1H), 4.54 (m, 1H), 6.85 (d, 2H), 7.23 (d, 2H); 13C NMR
(CDCl3) d 24.5, 26.2, 35.8, 36.9, 44.6, 55.5, 72.0, 78.9,
85.0, 111.7, 114.2, 129.7, 130.2, 159.0. Anal. calcd for
C16H22O4S: C, 61.91; H, 7.14; S, 10.33. Found: C,
62.03; H, 7.13; S, 10.15.
1
low foam: H NMR (CDCl3) d 1.96 (m, 1H), 2.05 (s,
3H), 3.28 (dt, 1H), 4.66 (m, 1H), 5.86 (m, 1H), 6.06 (d,
1H), 6.28 (d, 1H), 7.52-7.68 (m, 5H), 8.02 (m, 1H), 8.80
(s, 1H), 9.19 (s, 1H); 13C NMR (CDCl3) d 30.6, 39.7,
46.6, 58.8, 128.1, 128.8, 129.0, 130.3, 132.4, 133.8, 138.0,
141.5, 149.7, 151.9, 164.9, 195.0. Anal. calcd for
.
C19H17N5O2S 0.25CH3OH: C, 59.68; H, 4.68; N, 18.08;
S, 8.27. Found: C, 59.40; H, 4.78; N, 17.81; S, 7.90.
9-[(10R,20S,30S,40S)-40-S-(p-Methoxybenzyl)thio-20,30-(iso-
propylidenedioxy)-cyclopentan-10-yl]-adenine (15).
A
solution of diisopropyl azodicarboxylate (3.76 g, 17.7
mmol) in dry THF (30 mL) was added dropwise to a
solution of Ph3P (4.69 g, 17.7 mmol) in dry THF (50
mL). This was followed by stirring at room temperature
under N2 for 30 min. To this mixture was added 6-
chloropurine (2.51 g, 16.1 mmol). The mixture was stir-
(10R,20S,30S,40S)-N-[9-(20,30 -Dihydroxy-40 -S-acetylthio-
cyclopentyl)-9H-purin-6-yl]benzamide (10). To a solu-
tion of 9 (1.0 g, 2.6 mmol) in THF/H2O (1:1, 80 mL),
was added a 60% aqueous solution of NMO (1.08 g, 5.5
mol) and OsO4 (15 mg). The reaction mixture was stir-

460
S. R. Das et al. / Bioorg. Med. Chem. 10 (2002) 457–460
red for 30 min followed by the dropwise addition of a
solution of 14 (2.5 g, 16.1 mmol) in dry THF (30 mL).
The reaction mixture was stirred under N2 for 20 h. The
solvent was then evaporated and the residue purified by
column chromatography. Elution with 5:2hexane/
EtOAc yielded 9-[(10R,20S,30S,40S)-40-S-(p-methoxy-
benzyl)thio-20,30-(isopropylidenedioxy)cyclopentan-10-yl]-6-
chloropurine as a pale yellow solid that was used
directly in the next step.
Antiviral activity assays. The antiviral activity assays,
other than the anti-HBV assays, were based on the
inhibition of virus induced cytopathicity in either E6SM,
HeLa, Vero, CEM, or HEL cell cultures, following
previously established procedures.3b The anti-HBV
assays were performed as described previously.4
Acknowledgements
The obtained 9-[(10R,20S,30S,40S)-40-S-(p-methoxy-
benzyl)thio-20,30-(iso-propylidenedioxy)cyclopentan-10-yl]-
6-chloropurine was added to a saturated methanolic
NH3 solution (80 mL), which was sealed in a stainless
steel pressure vessel and heated at 110 ꢀC for 20 h. After
cooling to 0 ꢀC, the reaction vessel was opened and the
contents evaporated to dryness to obtain a white solid
residue, which was purified by column chromatography;
elution with 9:1 EtOAc/MeOH furnished 15 as a pale
yellow solid (2.45 g, 71% two steps): mp >160 ꢀC (dec);
1H NMR (CDCl3) d 1.29 (s, 3H), 1.55 (s, 3H), 2.08 (br,
1H), 2.44–2.61 (m, 1H), 3.16 (m, 1H), 3.76 (s, 3H), 3.80
(s, 2H), 4.77 (m, 2H), 5.11 (m, 1H), 5.82 (s, 2H), 6.86 (d,
2H), 7.29 (d, 2H), 7.87 (s, 1H), 8.34 (s, 1H); 13C NMR
(CDCl3) d 25.3, 27.5, 35.8, 37.4, 46.7, 55.5,61.3, 84.3,
87.0, 114.0, 114.2, 120.4, 130.1, 130.4, 139.8, 150.3,
153.1, 155.7, 159.0. Anal. calcd for C21H25N5O3S: C,
59.00; H, 5.89; N, 16.38; S, 7.50. Found: C, 58.92; H,
5.90; N, 16.27; S, 7.41.
This research was supported by funds from the Depart-
ment of Health and Human Services (AI 31718 and AI
48495) and this assistance is appreciated. We are
indebted to Brent Korba of Georgetown University
Medical Center, Rockville, Maryland for the anti-HBV
activity assays. We also express our gratitude to Dr.
Katherine Seley of the Georgia Institute of Technology
for assistance in obtaining the optical rotation data.
References and Notes
1. (a) For recent reviews see: Crimmins, M. T. Tetrahedron
1998, 54, 9229. (b) Zhu, X.-F. Nucleosides Nucleotides Nucleic
Acids 2000, 19, 651.
2. (a) Herdewijn, P.; De Clercq, E.; Balzarini, J.; Vander-
haeghe, H. J. Med. Chem. 1985, 28, 550. (b) Desgranges, C.;
Razaka, G.; Rabaud, M.; Bricaud, H.; Balzarini, J.; De
Clercq, E. Biochem. Pharmacol. 1983, 32, 3583.
3. (a) See, for example: Patil, S. D.; Schneller, S. W.; Hosoya,
M.; Snoeck, R.; Andrei, G.; Balzarini, J.; De Clercq, E. J.
Med. Chem. 1992, 35, 3372. (b) Siddiqi, S. M.; Chen, X.;
Schneller, S. W.; Ikeda, S.; Snoeck, R.; Andrei, G.; Balzarini,
J.; De Clercq, E. J. Med. Chem. 1994, 37, 551. (c) Siddiqi,
S. M.; Chen, X.; Schneller, S. W. Nucleosides Nucleotides
1993, 12, 267.
4. Seley, K. L.; Schneller, S. W.; Korba, B. Nucleosides
Nucleotides 1997, 16, 2095.
5. Hegde, V. R.; Seley, K. L.; Schneller, S. W.; Elder, T. J. J.
J. Org. Chem. 1998, 63, 7092.
6. Siddiqi, S. M.; Oertel, F. P.; Chen, X.; Schneller, S. W. J.
Chem. Soc., Chem. Commun. 1993, 708.
7. Siddiqi, S. M.; Chen, X.; Schneller, S. W.; Ikeda, S.;
Snoeck, R.; Andrei, G.; Balzarini, J.; De Clercq, E. J. Med.
Chem. 1994, 37, 1382.
8. (a) Hegde, V. R.; Schneller, S. W. Unpublished results. (b)
Seley, K. L.; Schneller, S. W.; Korba, B. J. Med. Chem. 1998,
41, 2168.
9. Divekar, S.; Safi, M.; Soufiaoui, M.; Sinou, D. Tetrahedron
1999, 55, 4369.
10. (a) Sammakia, T.; Hurley, T. B.; Sammond, D. M.; Smith,
R. S.; Sobolov, S. B.; Oeschger, T. R. Tetrahedron Lett. 1996,
37, 4427. (b) Das, S. R. Doctoral Dissertation, Auburn Uni-
versity, 2000.
11. (a) Kaldor, S. W.; Hammond, M. Tetrahedron Lett. 1991,
32, 5043. (b) Priebe, W.; Grynkiewicz, G. Tetrahedron Lett.
1991, 32, 7353.
(À)-(1R,2S 3S,4S)-4-Mercapto-1-(6-amino-9H-purin-9-
yl)cyclopentan-2,3-diol (6). Compound 15 (600 mg, 1.4
mmol) and phenol (190 mg, 2.1 mmol) were dissolved in
trifluoroacetic acid (6 mL), and this solution was stirred
and heated under reflux for 2h. The solution was eva-
porated, the residue re-dissolved in EtOH (10 mL) and
evaporated again. Column chromatography on the
residue (elution: 2:1, EtOAc/MeOH) furnished 6 (280
25
mg, 74.5%) as a white solid: mp > 210 ꢀC (dec.); ½ꢀꢂD
À12.90ꢀ (c 0.71, DMSO); H NMR (DMSO-d6) d 2.03
1
(m, 1H), 1.8 (m, 1H), 2.64 (m, 1H), 3.06 (br, 1H), 3.89
(m, 1H), 4.54 (m, 1H), 4.66 (m, 1H), 5.10 (d, 1H), 5.20
(d, 1H), 7.22 (s, 2H), 8.13 (s, 1H), 8.19 (s, 1H); 13C
NMR (DMSO-d6) d 36.7, 58.6, 59.5, 73.7, 78.9, 119.3,
140.3, 149.3, 152.1, 156.0. Anal. calcd for C10H13N5O2S:
C, 44.93; H, 4.90; N, 26.20; S, 11.99. Found: C, 45.06;
H, 5.03; N, 25.91; S, 11.80.
(+)-(1S,2R,3R,4R)-4-Mercapto-1-(6-amino-9H-purin-9-
yl)cyclopentan-2,3-diol (7). This was prepared from the
enantiomer of 1112 via a route analogous to that
described for 6. Physical data for 7: mp > 210 ꢀC (dec.);
25
½ꢀꢂD +14.20ꢀ (c 0.63, DMSO); H NMR (DMSO-d6) d
2.03 (m, 1H), 1.82 (m, 1H), 2.65 (m, 1H), 3.06 (m, 1H),
3.16 (d, 1H), 3.88 (m, 1H), 4.54 (m, 1H), 4.66 (m, 1H),
5.10 (d, 1H) 5.20 (d, 1H), 7.22 (s, 2H), 8.12 (s, 1H), 8.19
(s, 1H); 13C NMR (DMSO-d6) d 36.7, 58.5, 59.6, 73.7,
79.0, 119.3, 140.4, 149.4, 152.1, 155.9. Anal. calcd for
C10H13N5O2S: C, 44.93; H, 4.90; N, 26.20; S, 11.99.
Found: C, 44.96; H, 4.91; N, 26.09; N, 11.93.
1
12. Siddiqi, S. M.; Schneller, S. W.; Ikeda, S.; Snoeck, R.;
Andrei, G.; Balzarini, J.; De Clercq, E. Nucleosides Nucleo-
tides 1993, 12, 185.