Synthesis and antiviral evaluation of α-d-2′,3′- didehydro-2′,3′-dideoxy-3′-C-hydroxymethyl nucleosides

Article abstract of DOI:10.1016/j.bmcl.2010.08.071

We have identified a selective S_N2′ reaction triggered by iodide ion that leads to the ring-opening of 2,2′-anhydro-α- nucleosides. By applying the method, we have synthesized α-d-2′, 3′-didehydro-2′,3′-dideoxy-3′-C-hydroxymethyl nucleosides, d

Full text of DOI:10.1016/j.bmcl.2010.08.071

Bioorganic & Medicinal Chemistry Letters 20 (2010) 6013–6016
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis and antiviral evaluation of
-D-20,30-didehydro-20,30-dideoxy-30-C-hydroxymethyl nucleosides
a
Kohei Yamada a, , Hiroyuki Hayakawa a, Shinji Sakata a, Noriyuki Ashida a, Yuichi Yoshimura b,
⇑
⇑
a Biochemicals Division, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056, Japan
b Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
a r t i c l e i n f o
a b s t r a c t
We have identified a selective SN20 reaction triggered by iodide ion that leads to the ring-opening of
2,20-anhydro- -20,30-didehydro-20,30-
-nucleosides. By applying the method, we have synthesized
dideoxy-30-C-hydroxymethyl nucleosides, designed as potential antiviral agents.
Article history:
Received 8 July 2010
Revised 11 August 2010
Accepted 13 August 2010
Available online 21 August 2010
a
a-D
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Nucleosides
Antiviral
SN20 Reaction
For a few decades, sugar-modified nucleosides have provided
important leads for the development of novel antitumor and antiviral
agents.1 Among them, branched nucleosides with a 30-hydroxy-
methyl group, mimicking the oxetanose structure of the antibiotic
oxetanocin A2 (Fig. 1, Oxt-A, 1), were proven to have potent antiviral
activities: the ring-expanded oxetanocins 2 were synthesized, and
showed significantbiological activities.3 It has also been reported that
isonucleoside derivatives of 2, in which the base moiety is transposed
from the anomeric position to the 20-position, displayed antiviral
activities against Hepatitis B virus.4 Jeong and co-workers, on the
other hand, reported that ( )-apio-dideoxydidehydro nucleosides
(3; apio-d4Ns) showed potent anti-human cytomegalovirus (HCMV)
activity.5 Apio-d4 nucleosides 3 are considered to be 20,30-dideoxy-20-
oxo analogues of antiviral neplanocin A6 (NepA, 4). Drug design of 3
based on the structure of neplanocin A was reasonable since both 4
and its cytosine counterpart 5 were known to have potent antiviral
shown in Scheme 1, after protecting the primary hydroxyl group
of D-arabinose with a t-butyldiphenylsilyl group, introduction of
an acetal group at the O-1,2 positions gave acetal 7 in 51% yield.9
The secondary hydroxyl group of 7 was oxidized with DMSO/
Ac2O to give 8, which was treated with methylenetriphenylphos-
phorane to give 9 in 47% yield from 7.1j,1k Subsequent acetolysis
of 9 gave diacetate 10 (anomer ratio ꢀ 2:1) in 76% yield. Treatment
of 10 with trimethylsilylated thymine in the presence of trimethyl-
silyl trifluoromethanesulfonate (TMSOTf) at 60 °C gave the thymi-
dine derivative 11a in 83% yield. Only the a-anomer was formed in
this reaction due to participation of the 2-acetoxy group of 10. To
convert the secondary acetate 11a into the primary 12a, we next
examined the palladium-catalyzed allylic ester rearrangement.
We treated 11a with 10 mol % of palladium catalysts (e.g.,
(PPh3)2PdCl2, (CH3CN)2PdCl2, and Pd(PPh3)4) in THF under various
activity.6,7 Thus, the
a-D
-20,30-didehydro-20,30-dideoxy-30-C-hydroxy-
B
HO
B
O
methyl nucleosides 6, bearing the hydroxymethyl group at the C-40
position of apio-d4Ns 3 with an anti relationship to the nucleobase,
were expected to be potential antiviral agents. In this Letter, we de-
HO
n
O
HO
scribe the synthesis and antiviral evaluation of
20,30-dideoxy-30-C-hydroxymethyl nucleosides 6.
First, we attempted to synthesize 20-O-acetyl-30-C-methylene-
a-D
-20,30-didehydro-
1: n = 0, B = Ade (Oxt-A)
2: n = 1, B = nucleobases
3: R = H (Apio-d4Ns)
B
B
a
-arabinosyl thymine 11a starting from D-arabinose as a key inter-
HO
mediate for palladium-catalyzed allylic ester rearrangements.8 As
HO
O
HO OH
HO
⇑
Corresponding authors. Tel.: +81 479 22 0095; fax: +81 479 229821 (K.Y.); tel.:
4: B = Ade (NepA)
5: B = Cyt
6
+81 22 727 0145; fax: +81 22 275 2013 (Y.Y.).
E-mail addresses: k_yamada@yamasa.com (K. Yamada), yoshimura@tohoku-
pharm.ac.jp (Y. Yoshimura).
Figure 1.
0960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.08.071

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K. Yamada et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6013–6016
RO
O
RO
O
O
O
a,b
c
e
D-arabinose
O
O
X
HO
8: X = O
9: X = CH2
7
R = TBDPS
d
O
N
O
RO
O
NH
NH
RO
O
RO
O
N
g
OAc
f
O
O
OAc
R1
R1
AcO
OAc
10
11a: R1 = Me
11b: R1 = H
12a
Scheme 1. Reagents and conditions: (a) TBDPSCl, imidazole, DMF; (b) 2,2-dimethoxypropane, TsOHꢁH2O, acetone, 51% from
D
-arabinose; (c) Ac2O, DMSO; (d) Ph3P+CH3ꢁBrꢂ,
NaH, tert-amyl alcohol, 47% from 7; (e) AcOH, concd H2SO4, Ac2O, 76%; (f) silylated base, TMSOTf, CH2ClCH2Cl, 60 °C, 11a (83%), 11b; (g) 10 mol % Pd(PPh3)4, THF, reflux, 34%
(11a/12a = 2.3:1).
conditions from room temperature to reflux. However, the allylic
rearrangement of 11a using either Pd(II) or Pd(0) catalysts gave
only a mixture of isomers, which were difficult to separate. For
example, the reaction of 11a with 10 mol % of Pd(PPh3)4 under a re-
flux condition produced a mixture of 11a and 12a in a low yield
(34%, 11a/12a = 2.3:1), accompanied with the formation of more
polar byproducts. Due to the low reactivity of the allylic ester
substituted at the C-2 position,8 the conversion of 11a to 12a
was considered to be difficult. Thus, we needed an alternative ap-
proach to synthesize the target nucleosides.
Czernecki10 reported the synthesis of 30-C-azidomethyl branched
d4Ns using the SN20 opening of the 2,20-anhydro-b-nucleoside, in
which azide ion selectively attacked the exo-methylene group at
the C-30 position. These results suggest that soft anions, for example,
iodide and azide, preferentially attack at the 30-exo-methylene car-
bon by SN20 reaction and that hard anions, including benzoate, favor
SN2 attack at the 20-carbon. A similar tendency was reported by Mat-
suda and co-workers in the synthesis of 20-exo-methylene nucleo-
side analogues.11 Thus, it was considered that the SN20 reaction of
iodide ion was preferable than the SN2 reaction of benzoate ion
and that the desired d4-benzoate 15 should be formed by nucleo-
philic substitution of the iodomethyl derivative 19a (Scheme 3).
In this reaction, there seemed to be equilibrium between 17a
and 19a due to an intramolecular nucleophilic substitution by a
2-keto group of thymine to reproduce starting 14a. This may have
caused the reaction to give a mixture of 15a and 16a.
We next examined the SN20 type substitution reaction by ring-
opening of 2,20-anhydro-
a
-nucleosides (14a,b). As shown in Scheme
2, deacetylation of 11a by transesterification led to 13a, which was
converted into 2,20-anhydro-
-nucleoside 14a by mesylation of
the 20-hydroxyl group and subsequent intramolecular cyclization.
In the same way, 2,20-anhydro-
-nucleoside 14b was prepared from
diacetate 10. Initially, 2,20-anhydro-
-nucleoside 14a was treated
a
a
a
On the basis of this hypothesis, we anticipated that the SN20
reaction would proceed selectively if the intramolecular reaction
triggered by the 2-keto group could be suppressed. Thus, 2,20-
with excess benzoic acid and sodium benzoate in DMF at 130 °C (Ta-
ble 1, entry 1). However, only the undesired 16a was obtained in 64%
yield. The same result was obtained when the reaction was per-
formedusing non-polar tolueneas the solvent(entry 2). On the other
hand, reactioninthepresenceofiodideiongavea mixtureoftwoiso-
mers in 80–90% yield (15a/16a ꢀ 1:1, entries 3 and 4). Thus, to
obtain the desired SN20 adduct, the iodide ion appeared to be
important.
anhydro-a-nucleoside 14a was treated with sodium iodide and a
catalytic amount of benzoic acid (10 mol %) in the presence of
benzoic anhydride, which was expected to trap the N-3 nitrogen
of 19a generated along with the ring-opening reaction by benzoyl-
ation. To our delight, the reaction proceeded selectively and the de-
sired 15a was obtained as the major product (72% yield, 15a/
O
NH
R1
RO
O
TBDPSO
O
N
O
a
b
N
11a,b
O
R1
N
OH
O
R = TBDPS
13a: R1 = Me
13b: R1 = H
14a: R1 = Me
14b: R1 = H
c
O
O
NH
NH
RO
O
RO
O
N
O
N
O
+
R1
R1
BzO
OBz
15a: R1 = Me
15b: R1 = H
16a: R1 = Me
16b: R1 = H
Scheme 2. Reagents and conditions: (a) K2CO3, MeOH, 13a (98% from 11a), 13b (70% from 10); (b) MsCl, Et3N, CH3CN, 14a (76%), 14b (79%); (c) see Table 1.

K. Yamada et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6013–6016
6015
Table 1
The SN20 type substitution reaction via a ring-opening of 2,20-anhydro-
a
-nucleoside (14a)
Entry
Reagents
Solvent
Time (h)
Yielda (%)
Ratio (15a:16a)
1
2
3
4
5
BzONa, BzOH
BzOH
BzONa, BzOH, NaI
BzONa, TMSI
Bz2O, cat. BzOH, NaI
DMF
Toluene
DMF
DMF
DMF
9
7
3
3
4
64
84
83
90
72
Only 16a
Only 16a
1.4:1b
1:1b
23:1c
a
b
c
Isolated yields.
Ratio was determined based on integrations of 1H NMR analysis.
Ratio was determined based on isolated yields of two isomers.
Nu = hard anion: −OBz
O
N
R2
N
Me
Me
RO
O
RO
O
RO
O
Nu = −OBz
(slow)
N
N
O
O
O
N
H
N
O
O
OBz
16a: R2 = H
Me
Nu = soft anion: I−
17a
14a
18a: R2 = Bz
R = TBDPS
suppressed by
N3-benzoylation
Nu = I−
(fast)
O
R2
Me
N
RO
O
N
RO
O
O
N
O
(slow)
N
Me
O
R2
BzO
I
15a: R2 = H
21a: R2 = Bz
19a: R2 = H
20a: R2 = Bz
OBz
Scheme 3. Proposed mechanism for the selective benzoylation.
16a = 23:1, entry 5).12 Since only a trace amount of dibenzoate 21a
was isolated, the N3-benzoyl group of 21a seemed to be unstable
under the reaction conditions. Similarly, uracil derivative 14b
was converted into 15b in 84% yield. The 1H NMR spectrum of 15
showed no signals due to geminal vinylic protons, which were
present in the spectra of 14 and 16.
The C-30-methyl benzoate derivatives 15a,b in hand were
converted into the final pyrimidine apio-d4 nucleosides 6a,b, as
O
NH2
N
NH2
N
Me
N
N
N
c
a
b
O
N
O
15a,b
O
HO
HO
BzO
HO
HO
O
O
O
TBDPSO
6a
22
6b
NHBz
NH2
N
NHBz
N
N
N
N
N
N
R3O
N
N
N
N
g
N
d
h
10
HO
HO
BzO
TBDPSO
O
O
O
TBDPSO
6c
26
23: R3 = Ac
24: R3 = H
25: R3 = Ms
e
f
Scheme 4. Reagents and conditions: (a) (i) NH4OH, MeOH, THF, (ii) NH4FꢁHF, DMF, 70%; (b) TPSCl, Et3N, DMAP, CH3CN, and then NH4OH; (c) (i) NH4FꢁHF, DMF, (ii) NH4OH,
MeOH, THF, 72% from 15b; (d) N6-BzAdenine, SnCl4, CH3CN, 0 °C; (e) K2CO3, MeOH, 63% from 10; (f) MsCl, Et3N, CH3CN, 78%; (g) BzONa, NaI, DMF, 130 °C, 80%; (h) (i) TBAF,
THF; (ii) NH4OH, MeOH, THF, 64% from 15c.

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K. Yamada et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6013–6016
2. Shimada, N.; Hasegawa, S.; Harada, T.; Tomisawa, T.; Fujii, A.; Takita, T. J.
Antibiot. (Tokyo) 1986, 39, 1623.
shown in Scheme 4. Thymine derivative 6a was obtained in 70%
yield by debenzoylation and subsequent desilylation.13 Uracil
derivative 15b was aminated at the 4-position by treatment with
2,4,6-triisopropylbenzenesulfonyl chloride (TPSCl) in acetonitrile
in the presence of triethylamine and 4-(dimethylamino)pyridine
(DMAP), followed by aqueous ammonia, to give cytosine derivative
22. As with the thymine derivative, 22 was deprotected to give
apio-d4C derivative 6b in 72% yield from 15b.14 Next, we tried to
prepare a purine derivative using the above-mentioned reaction.
Treatment of diacetate 10 with N6-benzoyladenine and tin(IV)
chloride at 0 °C gave 23, which was subsequently deacetylated to
afford 24 in 63% yield from 10. Moreover, 24 was converted into
20-mesylate 25 in 78% yield. As we expected, the substitution reac-
tion of 20-mesylate 25 proceeded selectively to give only the de-
sired 26 in 80% yield. Attempted desilylation of 26 with
ammonium hydrogen fluoride in DMF was unsuccessful because
a deglycosylation reaction occurred even under the weakly acidic
conditions. Instead of using ammonium hydrogen fluoride, the
desilylation was successfully accomplished with TBAF, and subse-
quent debenzoylation gave the adenine derivative 6c in 64%
yield.15
3. (a) Svansson, L.; Kvarnstroem, I.; Classon, B.; Samuelsson, B. J. Org. Chem. 1991,
56, 2993; (b) Tseng, C. K. H.; Marquez, V. E.; Milne, G. W. A.; Wysocki, R. J., Jr.;
Mitsuya, H.; Shirasaki, T.; Driscoll, J. S. J. Med. Chem. 1991, 34, 343; (c)
Vanheusden, V.; Munier-Lehmann, H.; Froeyen, M.; Dugue, L.; Heyerick, A.; De
Keukeleire, D.; Pochet, S.; Busson, R.; Herdewijn, P.; Van Calenbergh, S. J. Med.
Chem. 2003, 46, 3811.
4. (a) Jung, M. E.; Nichols, C. J. J. Org. Chem. 1998, 63, 347; (b) Kakefuda, A.; Shuto,
S.; Nagahata, T.; Seki, J.; Sasaki, T.; Matsuda, A. Tetrahedron 1994, 50, 10167; (c)
Tino, J. A.; Clark, J. M.; Field, A. K.; Jacobs, G. A.; Lis, K. A.; Michalik, T. L.;
McGeever-Rubin, B.; Slusarchyk, W. A.; Spergel, S. H. J. Med. Chem. 1993, 36,
1221.
5. (a) Jeong, L. S.; Lee, Y. A.; Moon, H. R.; Yoo, S. J.; Kim, S. Y. Tetrahedron Lett. 1998,
39, 7517; (b) Jeong, L. S.; Kim, H. O.; Moon, H. R.; Hong, J. H.; Yoo, S. J.; Choi, W.
J.; Chun, M. W.; Lee, C.-K. J. Med. Chem. 2001, 44, 806.
6. Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi, M.; Otani, M. J.
Antibiot. (Tokyo) 1981, 34, 359.
7. Song, G. Y.; Paul, V.; Choo, H.; Morrey, J.; Sidwell, R. W.; Schinazi, R. F.; Chu, C. K.
J. Med. Chem. 2001, 44, 3985.
8. Overman, L. E. Angew. Chem., Int. Ed. Engl. 1984, 23, 579.
9. Doboszewski, B.; Herdewijn, P. Tetrahedron 2008, 64, 5551.
10. Similar allylic substitution has been reported: (a) Czernecki, S.; Ezzitouni, A. J.
Org. Chem. 1992, 57, 7325; (b) Czernecki, S.; Ezzitouni, A. Tetrahedron Lett.
1993, 34, 315.
11. (a) Hassan, A. A. A.; Matsuda, A. Heterocycles 1992, 34, 657; (b) Hassan, A. A. A.;
Shuto, S.; Matsuda, A. Tetrahedron 1994, 50, 689.
12. Procedure of the preparation of 15a: To a solution of 14a (200 mg, 0.42 mmol) in
DMF (12 ml), sodium iodide (189 mg, 1.26 mmol), benzoic anhydride (285 mg,
3.75 mmol) and benzoic acid (15 mg, 0.04 mmol) were added, and the mixture
was stirred at 130 °C for 4 h. Solvent was removed under reduced pressure, and
the residue was extracted with AcOEt, and the organic phase was washed with
saturated NaHCO3, water and brine, and then dried (Na2SO4). The solvent was
removed under reduced pressure, and the residue was purified by column
chromatography over silica gel (2.2 ꢃ 13 cm, 30–50% AcOEt in n-hexane) to
give 15a (174 mg, 69%) and 16a (9 mg, 3%) as an amorphous foam, respectively.
13. Data for 6a: white solid. Mp 160 °C; UV (MeOH): kmax 265 nm; 1H NMR
(400 MHz, DMSO-d6): d 11.27 (1H, s, NH), 7.16 (1H, d, H-6, J = 1.5 Hz), 6.82–
6.81 (1H, m, H-10), 5.63 (1H, t, H-20, J = 1.5 Hz), 5.09 (1H, t, OH, J = 5.4 Hz), 4.94
(1H, br s, H-40), 4.77 (1H, dd, OH, J = 5.4, 6.4 Hz), 4.17–4.13 (2H, m, H-allyl),
3.56 (1H, ddd, H-50a, J = 3.9, 5.4, 12.2 Hz), 3.44 (1H, ddd, H-50b, J = 3.9, 6.4,
12.2 Hz), 1.77 (1H, d, Me, J = 1.5 Hz); 13C NMR (125 MHz, DMSO-d6): 163.8,
150.6, 149.7, 135.8, 118.7, 109.6, 88.8, 86.6, 62.0, 56.7, 12.0; FAB-MS (m/z) 255
(M++H); HR-ESIMS (m/z). Calcd for [C11H14N2O5Na]+: 277.0800; found:
277.0820. Anal. Calcd for C11H14N2O5: C, 51.97; H, 5.55; N, 11.02. Found: C,
51.80; H, 5.61; N, 10.94.
In conclusion, we describe a selective SN20 reaction triggered by
iodide ion that leads to the ring-opening of 2,20-anhydro-
a
-nucleo-
sides (14). By applying the method, we have synthesized a-D
-20,30-
didehydro-20,30-dideoxy-30-C-hydroxymethyl nucleosides (6).
These nucleosides were assayed for antiviral activities against sev-
eral viruses, such as HIV-1, herpes simplex virus (HSV) types-1,2,
and HCMV.16 Although the thymine derivative 6a was found to ex-
hibit very weak anti-HSV type-1 activity (EC50 = 33
lg/mL, CC50
>100 g/mL), none of the other compounds that we tested showed
l
any antiviral activity or cytotoxicity. To clarify the reason why
these nucleosides except 6a were inactive, the further study on
their structure–activity relationships should be needed.
Acknowledgment
14. Data for 6b: amorphous foam. UV (MeOH): kmax 238, 272 nm; 1H NMR
(400 MHz, DMSO-d6): d 7.34 (1H, d, H-6, J = 7.3 Hz), 7.16 (1H, br s, NH), 7.11
(1H, br s, NH), 6.88–6.86 (1H, m, H-10), 5.72 (1H, d, H-5, J = 7.3 Hz), 5.64 (1H, t,
H-20, J = 1.5 Hz), 5.06 (1H, t, OH, J = 5.4 Hz), 4.91–4.90 (1H, m, H-40), 4.78 (1H, t,
OH, J = 5.9 Hz), 4.18–4.08 (2H, m, H-allyl), 3.56 (1H, ddd, H-50a, J = 3.9, 5.9,
11.7 Hz), 3.46 (1H, ddd, H-50b, J = 4.4, 5.9, 11.7 Hz); 13C NMR (125 MHz, DMSO-
d6): 165.6, 155.3, 148.7, 141.0, 119.9, 94.3, 89.5, 86.4, 62.2, 56.7; FAB-MS (m/z)
240 (M++H); HR-ESIMS (m/z). Calcd for [C10H13N3O4Na]+: 262.0804; found:
262.0847. Anal. Calcd for C10H13N3O4ꢁ0.6H2O: C, 48.04; H, 5.72; N, 16.81.
Found: C, 48.03; H, 5.86; N, 17.02.
We are grateful to Dr. K. Kodama of Yamasa Corporation for his
encouragement throughout this work.
References and notes
1. See, for example: (a) Yoshimura, Y.; Asami, K.; Imamichi, T.; Kuroda, T.; Shiraki,
K.; Tanaka, H.; Takahata, H. J. Org. Chem. 2010, 75, 4161; (b) Yoshimura, Y.;
Yamazaki, Y.; Saito, Y.; Takahata, H. Tetrahedron 2009, 65, 9091; (c) Yoshimura,
Y.; Ohta, M.; Imahori, T.; Imamichi, T.; Takahata, H. Org. Lett. 2008, 10, 3449; (d)
Yoshimura, Y.; Asami, K.; Matsui, H.; Tanaka, H.; Takahata, H. Org. Lett. 2006, 8,
6015; (e) Yoshimura, Y.; Kitano, K.; Yamada, K.; Sakata, S.; Miura, S.; Ashida, N.;
Machida, H. Bioorg. Med. Chem. 2000, 8, 1545; (f) Yoshimura, Y.; Endo, M.;
Miura, S.; Sakata, S. J. Org. Chem. 1999, 64, 7912; (g) Yamada, K.; Sakata, S.;
Yoshimura, Y. J. Org. Chem. 1998, 63, 6891; (h) Satoh, H.; Yoshimura, Y.; Sakata,
S.; Miura, S.; Machida, H.; Matsuda, A. Bioorg. Med. Chem. Lett. 1998, 8, 989; (i)
Yoshimura, Y.; Watanabe, M.; Satoh, H.; Ashida, N.; Ijichi, K.; Sakata, S.;
Machida, H.; Matsuda, A. J. Med. Chem. 1997, 40, 2177; (j) Yoshimura, Y.; Kitano,
K.; Yamada, K.; Satoh, H.; Watanabe, M.; Miura, S.; Sakata, S.; Sasaki, T.;
Matsuda, A. J. Org. Chem. 1997, 62, 3140; (k) Yoshimura, Y.; Kitano, K.; Satoh, H.;
Watanabe, M.; Miura, S.; Sakata, S.; Sasaki, T.; Matsuda, A. J. Org. Chem. 1996,
61, 822; (l) Yoshimura, Y.; Saitoh, K.; Ashida, N.; Sakata, S. Bioorg. Med. Chem.
Lett. 1994, 4, 721.
15. Data for 6c: amorphous foam. UV (MeOH): kmax 261 nm; 1H NMR (400 MHz,
DMSO-d6): d 8.16 (1H, s, H-2 or H-8), 8.08 (1H, s, H-8 or H-2), 7.24 (2H, br s,
NH2), 6.94–6.93 (1H, m, H-10), 5.90 (1H, t, H-20, J = 1.5 Hz), 5.11 (1H, br s, OH),
5.00 (1H, br s, H-40), 4.81 (1H, br s, OH), 4.25–4.15 (2H, m, H-allyl), 3.63–3.51
(2H, m, H-50); 13C NMR (125 MHz, DMSO-d6): 155.9, 152.6, 149.4, 149.0, 138.4,
118.9, 118.6, 87.2, 86.5, 62.0, 56.8; FAB-MS (m/z) 264 (M++H); HR-ESIMS (m/z).
Calcd for [C11H13N5O3Na]+: 286.0916; found: 286.0939. Anal. Calcd for
C
11H13N5O3ꢁ0.1H2O: C, 49.85; H, 5.02; N, 26.42. Found: C, 49.87; H, 4.93; N,
26.54.
16. Antiviral activities, except against HIV, and cytotoxicities were assayed at the
Biological Laboratory of Yamasa Corp. Anti-HIV activity was tested at the
Rational Drug Design Laboratories, Fukushima, Japan. We greatly appreciate
the assistance of the staff there.