Asymmetric synthesis of homo-apioneplanocin A from d-ribose

Article abstract of DOI:10.1016/j.tet.2006.04.042

Homo-apioneplanocin A was efficiently synthesized via stereoselective hydroxymethylation, regio- and chemoselective hydroboration, and chemoselective oxidation as key steps from d-ribose.

Full text of DOI:10.1016/j.tet.2006.04.042

Tetrahedron 62 (2006) 6339–6342
Asymmetric synthesis of homo-apioneplanocin A from D-ribose
Jin-Hee Kim,a Hea Ok Kim,b Kang Man Lee,b Moon Woo Chun,a
Hyung Ryong Moonc and Lak Shin Jeongb,
*
aCollege of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
bLaboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea
cCollege of Pharmacy, Pusan National University, Busan 609-753, Republic of Korea
Received 4 March 2006; revised 12 April 2006; accepted 12 April 2006
Available online 8 May 2006
Abstract—Homo-apioneplanocin A was efficiently synthesized via stereoselective hydroxymethylation, regio- and chemoselective hydro-
boration, and chemoselective oxidation as key steps from D-ribose.
Ó 2006 Elsevier Ltd. All rights reserved.
NH2
N
NH2
N
1. Introduction
NH2
N
N
N
N
N
N
N
(ꢀ)-Neplanocin A (NPA), originally isolated from the
culture filtrate of the soil fungus Ampullariella regularis,1
is a carbocyclic nucleoside in which a methylene group
replaces the oxygen atom in the furanose ring and one of
the most potent S-adenosylhomocysteine (AdoHcy) hydro-
lase inhibitors.2 NPA has been reported to possess a signifi-
cant antiviral effect3 correlating with the inhibition of
AdoHcy hydrolase, but it was too cytotoxic to be a clinically
useful antiviral agent.2b,4
HO
HO
N
N
N
O
HO
HO
Homoneplanocin A
OH
HO
OH
Apio-ddA
(-)-Neplanocin A
NH2
NH2
N
N
N
N
N
N
N
Moreover, it is known to undergo deamination by adenosine
deaminase to the biologically inactive compound, the ino-
sine congener.5
N
HO
HO
HO
OH
HO
OH
Homo-apioneplanocin A
Apioneplanocin A
Apionucleoside has a unique sugar moiety, in that the
40-hydroxymethyl group of the sugar is shifted to the C30-
position.6–9 Apio-ddA has been reported to show potent
anti-AIDS activity comparable to that of the parent nucleo-
side, 20,30-dideoxyadenosine (ddA) and better stability of the
glycosidic bond under acidic conditions than ddA.8b In order
to search for potent inhibitors of AdoHcy hydrolase, we have
recently synthesized the apioneplanocin A (apio-NPA),10
which combines the structural characteristics of NPA and
apionucleoside, but this compound showed neither a signifi-
cant antiviral activity nor inhibitory activity against AdoHcy
hydrolase.
(1, HANPA)
Figure 1. The rational for the design of the desired nucleoside, HANPA (1).
activity against AdoHcy hydrolase, we designed the homo-
apioneplanocin A (HANPA, 1), which combined apionepla-
nocin A and 60-homoneplanocin A as a potential inhibitor of
AdoHcy hydrolase (Fig. 1). Herein, we wish to describe the
asymmetric synthesis of HANPA (1) from D-ribose via
stereoselective hydroxymethylation, regio- and chemoselec-
tive hydroboration, and chemoselective oxidation as key
steps.
However, since another NPA-modified compound, 60-homo-
neplanocin A11 was reported to have a significant inhibitory
2. Results and discussion
Keywords: Homo-apioneplanocin A; Stereoselective hydroxymethylation;
Chemoselective hydroboration; Chemoselective oxidation.
* Corresponding author. Tel.: +82 2 3277 3466; fax: +82 2 3277 2851;
e-mail: lakjeong@ewha.ac.kr
The synthetic strategy of the target compound 1 is outlined
in Scheme 1. It was envisioned that dienyl diols 410 could
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.042

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J.-H. Kim et al. / Tetrahedron 62 (2006) 6339–6342
be an appropriate intermediate, efficiently synthesized by
our laboratory, for the final compound.
a
ref. 10
O
HO
OH
OH
HO
O
O
O
O
O
O
O
NH2
7
8
5
N
N
O
N
b
OH
O
OH
H
N
O
RO
c
O
O
d
HO
OH
O
OH
OH
31%
71%
2
O
O
3
HO OH
HANPA (1)
from 7
O
O
O
O
e
11 (R = H)
12 (R = Tr)
10
9
76%
O
HO
O
HO
f
96%
OH
OH
HO
O
O
O
O
HO
OH
TrO
OTs
5
D-Ribose
4
O
O
Scheme 1. Retrosynthetic analysis of the desired nucleoside, HANPA (1).
13
Our initial approach was to introduce the hydroxyethyl
group at C3-position of 5 directly in the stereoselective
manner, as depicted in Scheme 2. Treatment of 5 with 2-tri-
tyloxyethyl bromide and 2-tert-butyldimethylsilyloxyethyl
bromide in the presence of various bases such as LDA,
LiHMDS, and K2CO3 at various temperatures such as ꢀ78
and 80 ꢁC in THF failed to produce the desired product 6
or afforded 6 in less than 5% yield.
Scheme 3. Reagents and conditions: (a) TEMPO, TBACl, NCS, aqueous
NaHCO3 and K2CO3 (pH¼8.6), CH2Cl2, rt, 3 h; (b) second generation
Grubbs catalyst, CH2Cl2, rt, 5 h; (c) MePh3PBr, KOt-Bu, THF, rt, 12 h;
(d) (i) Sia2BH, THF, from 0 ꢁC to rt, 16 h; (ii) NaBO3$H2O, rt, 12 h;
(e) TrCl, pyridine, DMAP, rt, 24 h; (f) TsCl, DMAP, CH2Cl2, rt, 24 h.
Condensation of 13 with adenine in the presence of K2CO3
and 18-crown-6 in DMF afforded the N-9 isomer 14 as a
major product (78%) along with its N-7 isomer 15 (3%) after
the separation by silica gel column chromatography
(Scheme 4). The regio-isomers 14 and 15 were easily as-
signed based on the comparison with UV literature data.15
Removal of the protecting groups of 14 under acidic condi-
tions produced the desired product 1.
O
O
OR
R = Tr or TBS
HO
HO
Br
RO
O
O
O
O
6a; R = Tr
6b; R = TBS
5
NH2
Scheme 2. Attempted methods for the direct introduction of hydroxyethyl
functional group.
N
N
N
N
N
N
TrO
N
a
OTs
+
Thus, another route including stereoselective hydroxy-
methylation, regioselective oxidation, Wittig reaction, and
chemoselective hydroboration was employed to introduce
hydroxyethyl group stereoselectively at C3-position
(Scheme 3). Lactol 5 was converted to diol 7 as a single
diastereoisomer according to our previously reported proce-
dure.10
N
O
O
TrO
NH2
TrO
13
O
O
O
O
15 (3%)
14 (78%)
b
41%
NH2
N
N
Chemoselective oxidation of diol 7 to aldehyde 8 was
achieved by treating with TEMPO, TBACl, and NCS under
pH 8.6.12 Ring-closing metathesis (RCM)13 of 8 with second
generation Grubbs catalyst afforded cyclopentenal 9.
However, RCM reaction of 7 gave the cyclopentene diol in
good yield, but chemoselective oxidation of the diol failed
to give the desired product 9. Wittig reaction of 9 under
the standard conditions gave vinylcyclopentenol 10. Various
hydroboration reagents were attempted to accomplish regio-
and chemoselective hydroboration. Hydroboration of 10
using catecholborane and Wilkinson catalyst Rh(PPh3)3Cl
(rhodium-catalyzed olefin hydroboration) in THF14 or
9-BBN in THF did not give the desired alcohol 11, while
treatment with Sia2BH gave the desired product 11 in
good yield (71%) after oxidation with sodium perborate.
Selective protection of the primary hydroxyl group of 11
with a bulky trityl group followed by tosylation of the
resulting 12 gave the glycosyl donor 13.
N
N
HO
HO
OH
1
Scheme 4. Reagents and conditions: (a) adenine, K2CO3, 18-crown-6, DMF,
80 ꢁC, 12 h; (b) 1% HCl, MeOH, rt, 12 h.
Inhibitory activity of AdoHcy hydrolase by compound 1 was
measured using pure recombinant enzyme obtained from
human placenta. Compound 1 did not exhibit significant
inhibitory activity against AdoHcy hydrolase, although
we expected the hydroxyethyl side chain of 1 to induce the
favorable binding to AdoHcy hydrolase. This lack of enzyme
inhibitory activity might be attributed to the presence of the
tertiary hydroxyl group at the C3-position, which should be
oxidized by cofactor-bound NAD+.

J.-H. Kim et al. / Tetrahedron 62 (2006) 6339–6342
6341
3. Conclusions
17.3 Hz), 5.15 (dd, 1H, J¼1.1, 10.6 Hz), 4.61 (tdd, 1H,
J¼1.6, 5.1, 10.6 Hz), 4.43 (d, 1H, J¼5.1 Hz), 2.64 (d, 1H,
J¼10.6 Hz), 1.42 (s, 6H); 13C NMR (CDCl3) d 137.9,
135.6, 134.0, 115.6, 112.6, 94.0, 82.6, 74.6, 27.8, 27.5;
LRMS (ESI) m/z 205 [M+Na]+; Anal. Calcd for
C10H14O3: C, 65.91; H, 7.74. Found: C, 66.04; H, 7.60.
Asymmetric synthesis of homo-apioneplanocin A (1,
HANPA) was efficiently achieved using stereoselective
hydroxylation, chemoselective oxidation, and regio- and
chemoselective hydroboration as key steps from D-ribose.
To our best knowledge, homo-apioneplanocin A is the first
example of carbocyclic nucleosides with unnatural homo-
apio carbasugar.
4.1.2. (+)-(1S,2S,3R)-2,3-O-Isopropylidene-3-(2-hydroxy)-
ethyl-4-cyclopentenol (11). 2-Methyl-2-butene (9.2 mL,
18.4 mmol, 2 M solution in THF) was added to borane–
dimethyl sulfide (4.6 mL, 9.2 mmol, 2 M solution in THF)
and the reaction mixture was stirred at 0 ꢁC for 2.5 h. The
resulting solution was added dropwise through a cannula
to a stirred solution of 10 (712 mg, 3.91 mmol) in THF
(5 mL) at 0 ꢁC and the mixture was stirred at room tempera-
ture for 16 h. NaBO3$H2O (1.512 g, 15.15 mmol) and H2O
(8 mL) were added carefully, and the mixture was stirred
at room temperature for 12 h. The mixture was partitioned
between water and CH2Cl2. The organic layer was dried over
MgSO4, filtered, and evaporated. The resulting residue was
purified by silica gel column chromatography (hexane/ethyl
acetate¼1:3) to give 11 (559 mg, 71%) as a white solid; mp
4. Experimental
4.1. General
Melting points are uncorrected. NMR data were recorded on
a 300, 400, and 500 MHz NMR spectrometer using tetra-
methylsilane (TMS) as an internal standard, and the chemi-
cal shifts are reported in parts per million (d). Coupling
constants are reported in Hertz. The abbreviations used are
as follows: s (singlet), d (doublet), m (multiplet), dd (doublet
of doublet), and br s (broad singlet). All the reactions
described below were performed under argon or nitrogen
atmosphere and monitored by thin layer chromatography
(TLC, Silica gel 60 F254). All anhydrous solvents were
distilled over CaH2 or Na/benzophenone prior to use.
1
81.9 ꢁC; [a]D25 +20.1 (c 1.52, MeOH); H NMR (CDCl3)
d 5.84 (d, 1H, J¼5.9 Hz), 5.81 (d, 1H, J¼5.9 Hz), 4.62 (s,
1H), 4.49 (d, 1H, J¼4.9 Hz), 3.79 (m, 1H), 3.71 (m, 1H),
2.87 (s, 1H), 2.74 (s, 1H), 1.97 (m, 2H), 1.44 (s, 3H), 1.41
(s, 3H); 13C NMR (CDCl3) d 135.0, 134.7, 111.9, 93.8,
82.1, 74.3, 59.2, 38.2, 27.9, 27.9; IR (KBr): 3395, 2922,
1646, 1372, 1105, 893, 615 cmꢀ1; LRMS (FAB) m/z 201
[M+H]+; HRMS calcd for C10H17O4 [M+H]+: 201.1129,
found: 201.1126; Anal. Calcd for C10H16O4: C, 59.98; H,
8.05. Found: C, 59.61; H, 8.19.
4.1.1. (L)-(1S,2S,3R)-2,3-O-Isopropylidene-3-vinyl-4-
A solution of diol 7 (3.09 g,
cyclopentenol (10).
14.47 mmol), TEMPO (226 mg, 1.45 mmol), and tetrabutyl-
ammonium chloride (403 mg, 1.45 mmol) in methylene
chloride (100 mL) and an aqueous solution (100 mL) of
0.5 M NaHCO3 and 0.05 M K2CO3 were vigorously stirred
at room temperature. After adding N-chlorosuccinimide
(2.125 g, 15.9 mmol) to the mixture, the mixture was stirred
at room temperature for 3 h. The organic layer was separated
and the aqueous layer was extracted with CH2Cl2. The com-
bined organic layers were washed with brine, dried
(MgSO4), and evaporated. The resulting residue was purified
by silica gel column chromatography (hexane/ethyl
acetate¼3:1) to give 8 as a colorless oil, which was immedi-
ately used for the next step. To a stirred solution of 8 in
CH2Cl2 (25 mL) was added second generation Grubbs cata-
lyst (7 mg, 0.07 mmol) at room temperature and the reaction
mixture was stirred at room temperature for 5 h and evapo-
rated to give a brown residue. The resulting residue was
purified by silica gel column chromatography (hexane/ethyl
acetate¼1:3) to give cyclopentenal 9 as a colorless oil,
which was immediately used for the next step. To a stirred
suspension of CH3PPh3Br (6.058 g, 16.62 mmol) in THF
(80 mL) was added potassium tert-butoxide (16.6 mL,
16.60 mmol, 1 M solution in THF) at 0 ꢁC and the mixture
was stirred at room temperature for 1 h . To this stirred solu-
tion was added a solution of cyclopentenal 9 in THF (30 mL)
through a cannula at 0 ꢁC, and the reaction mixture was
stirred at room temperature for 12 h. The reaction mixture
was partitioned between water and ethyl acetate and the
organic layer was dried over anhydrous MgSO4, filtered,
and evaporated. The resulting residue was purified by silica
gel column chromatography (hexane/ethyl acetate¼3:1) to
give diene 10 (826 mg, 31% over three steps) as a colorless
4.1.3. (+)-(1S,2S,3R)-2,3-O-Isopropylidene-3-(2-triphe-
nylmethyloxy)ethyl-4-cyclopentenol (12). A solution of
cyclopentenol 11 (482 mg, 2.4 mmol), trityl chloride
(1.338 g, 4.8 mmol), and 4-(dimethylamino)pyridine (61 mg,
0.5 mmol) in pyridine (15 mL) was stirred at room tempera-
ture for 24 h. The reaction mixture was partitioned between
water and ethyl acetate and the organic layer was dried
over anhydrous MgSO4, filtered, and evaporated. The result-
ing residue was purified by silica gel column chromato-
graphy (hexane/ethyl acetate¼5:1) to give 12 (807 mg,
76%) as a white solid; mp 135.8 ꢁC; [a]D25 +17.1 (c 2.57,
1
CHCl3); H NMR (CDCl3) d 7.30 (m, 15H), 5.64 (d, 1H,
J¼5.8 Hz), 5.58 (d, 1H, J¼5.8 Hz), 4.55 (d, 1H,
J¼5.0 Hz), 4.47 (tdd, 1H, J¼1.3, 5.0, 10.4 Hz), 3.23 (td,
1H, J¼5.8, 11.4 Hz), 2.97 (m, 1H), 2.62 (d, 1H,
J¼10.4 Hz), 2.12 (ddd, 1H, J¼6.0, 7.9. 14.1 Hz), 1.97 (td,
1H, J¼5.6, 14.2 Hz), 1.33 (s, 3H), 1.31 (s, 3H); 13C NMR
(CDCl3) d 144.0, 135.1, 135.1, 128.5, 127.8, 127.0, 111.4,
96.1, 93.3, 87.2, 82.1, 74.5, 60.0, 36.6, 28.0, 28.0; IR (KBr)
3543, 2986, 2931, 1489, 1448, 1376, 1221, 1066 cmꢀ1
;
LRMS (ESI) m/z 465 [M+Na]+; Anal. Calcd for C29H30O4:
C, 78.71; H, 6.83. Found: C, 78.45; H, 6.81.
4.1.4. (L)-(1S,2S,3R)-2,3-O-Isopropylidene-3-(2-triphe-
nylmethyloxy)ethyl-4-cyclopentenyl p-toluenesulfonate
(13). To a stirred solution of 12 (473 mg, 1.07 mmol)
and 4-(dimethylamino)pyridine (395 mg, 3.23 mmol) in
CH2Cl2 (15 mL) was added TsCl (416 mg, 2.18 mmol).
After being stirred at room temperature for 24 h, the reaction
mixture was partitioned between water and CH2Cl2. The
1
oil: [a]2D5 ꢀ32.9 (c 0.1, CHCl3); H NMR (CDCl3) d 5.94
(dd, 1H, J¼10.6, 17.3 Hz), 5.8 (td, 1H, J¼0.8, 5.7 Hz),
5.75 (ddd, 1H, J¼0.6, 1.6, 5.7 Hz), 5.24 (dd, 1H, J¼1.1,

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J.-H. Kim et al. / Tetrahedron 62 (2006) 6339–6342
organic layer was dried over anhydrous MgSO4, filtered, and
evaporated. The resulting residue was purified by silica gel
column chromatography (hexane/ethyl acetate¼3:1) to
give tosylate 13 (614 mg, 96%) as a white solid; mp
153.8, 157.5; LRMS (EI) m/z 277 [M]+; HRMS calcd for
C12H12N5O3: 277.1175, found: 277.1178.
1
133.4 ꢁC; [a]D25 ꢀ0.6 (c 1.18, CHCl3); H NMR (CDCl3)
Acknowledgements
d 7.41 (m, 19H), 5.67 (dd, 1H, J¼1.6, 5.8 Hz), 5.42 (dd,
1H, J¼0.9, 5.8 Hz), 5.16 (td, 1H, J¼1.6, 5.4 Hz), 4.71 (d,
1H, J¼4.9 Hz), 3.22 (td, 1H, J¼4.9, 9.9 Hz), 2.80 (dt, 1H,
J¼3.9, 9.5 Hz), 2.48 (s, 3H), 2.15 (qd, 1H, J¼4.6,
14.4 Hz), 1.89 (td, 1H, J¼4.1, 14.4 Hz), 1.28 (s, 3H), 1.27
(s, 3H); 13C NMR (CDCl3) d 144.3, 143.7, 138.4, 129.7,
129.5, 128.4, 128.0, 127.9, 127.0, 111.8, 93.1, 87.3, 81.5,
81.5, 59.7, 36.1, 28.0, 27.6, 21.6; IR (KBr): 2927, 1597,
1449, 1368, 1179, 1073, 997 cmꢀ1; LRMS (ESI) m/z 619
[M+Na]+.
This work was supported by a grant from Korea Research
Foundation (KRF-2005-005-J01502).
References and notes
1. Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi, M.;
Otani, M. J. Antibiot. 1981, 34, 359–366.
2. (a) Borchardt, R. T.; Keller, B. T.; Patel-Thombre, U. J. Biol.
Chem. 1984, 259, 4353–4358; (b) De Clercq, E. Antimicrob.
Agents Chemother. 1985, 28, 84–89.
4.1.5. (L)-(3R,4S,5S)-3,4-O-Isopropylidene-3-(2-triphe-
nylmethyloxy)ethyl-5-(adenin-9-yl)-cyclopentene (14)
and its N-7 isomer (15). A stirred suspension of adenine
(36 mg, 0.26 mmol), 18-crown-6 (69 mg, 0.26 mmol), and
K2CO3 (54 mg, 0.39 mmol) in DMF (2 mL) was heated at
80 ꢁC for 30 min. To this clear solution was added a solution
of tosylate 13 (77 mg, 0.13 mmol) in DMF (3 mL) at 80 ꢁC
and the reaction mixture was heated at 80 ꢁC for 12 h. The
reaction mixture was cooled to room temperature and parti-
tioned between water and CH2Cl2. The organic layer was
dried over anhydrous MgSO4, filtered, and evaporated. The
resulting residue was purified by silica gel column chroma-
tography (methylene chloride/methanol¼30:1) to give 14
(57 mg, 78%) as a white solid and 15 (2 mg, 3%).
3. Cools, M.; De Clercq, E. Biochem. Pharmacol. 1989, 38, 1061–
1067.
4. (a) Glazer, R. I.; Knode, M. C. J. Biol. Chem. 1984, 259, 12964–
12969; (b) Inaba, M.; Nagashima, K.; Tsukagoshi, S.; Sakurai, Y.
Cancer Res. 1986, 46, 1063–1067; (c) De Clercq, E.; Murase, J.;
Marquez, V. Biochem. Pharmacol. 1991, 41, 1821–1829.
5. Shuto, S.; Obara, T.; Toriya, M.; Hosoya, M.; Snoeck, R.;
Andrei, G.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1992,
35, 324–331.
6. Nair, V.; Jahnke, T. S. Antimicrob. Agents Chemother. 1995, 39,
1017–1029.
7. Bamford, M. J.; Humber, D. C.; Storer, R. Tetrahedron Lett.
1991, 32, 271–274.
8. (a) Sells, T. B.; Nair, V. Tetrahedron Lett. 1993, 34, 3527–3530;
(b) Terao, Y.; Akamatsu, M.; Achiwa, K. Chem. Pharm. Bull.
1991, 39, 823–825.
9. (a) Jeong, L. S.; Lee, Y. A.; Moon, H. R.; Chun, M. W.
Nucleosides Nucleotides 1998, 17, 1473–1487; (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, 806–813.
10. (a) Moon, H. R.; Kim, H. O.; Lee, K. M.; Chun, M. W.; Kim,
J. H.; Jeong, L. S. Org. Lett. 2002, 4, 3501–3503; (b) Lee,
J. A.; Moon, H. R.; Kim, H. O.; Kim, K. R.; Lee, K. M.;
Kim, B. T.; Hwang, K. J.; Chun, M. W.; Jacobson, K. A.;
Jeong, L. S. J. Org. Chem. 2005, 70, 5006–5013.
11. (a) Shuto, S.; Obara, T.; Saito, Y.; Andrei, G.; Snoeck, R.; De
Clercq, E.; Matsuda, A. J. Med. Chem. 1996, 39, 2392–2399;
(b) Yang, M.; Schneller, S. W.; Korba, B. J. Med. Chem.
2005, 48, 5043–5046.
12. Klimko, P. G.; Hellberg, M. R.; Falck, J. R.; Conrow, R. E.
Preparation of hydroxyeicosatetraenoic acid analogs and
methods of their use in treating dry eye disorders. U.S. Patent
Appl. 35095, 2002, 34 pp.
13. (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450;
(b) Grubbs, R. H. Tetrahedron 2004, 60, 7117–7140.
14. (a) Yasuike, S.; Kofink, C. C.; Kloetzing, R. J.; Gommermann,
N.; Tappe, K.; Gavryushin, A.; Knochel, P. Tetrahedron: Asym-
metry 2005, 16, 3385–3393; (b) Widauer, C.; Grutzmacher, H.;
Ziegler, T. Organometallics 2000, 19, 2097–2107; (c) Mannig,
D.; Noth, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878–879;
(d) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179–
1191; (e) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am.
Chem. Soc. 1992, 114, 6671–6679.
Compound 14: mp 77.1 ꢁC; [a]D25 ꢀ52.9 (c 0.1, CHCl3); UV
(CHCl3) lmax 260 nm; 1H NMR (CDCl3) d 8.44 (s, 1H), 7.62
(s, 1H), 7.24 (m, 15H), 6.29 (dd, 1H, J¼1.2, 5.7 Hz), 5.94
(dd, 1H, J¼2.0, 5.7 Hz), 5.64 (br s, 2H), 5.57 (s, 1H), 4.49
(s, 1H), 3.29 (t, 2H, J¼6.4 Hz), 2.05 (t, 2H, J¼6.5 Hz),
1.39 (s, 3H, CH3), 1.22 (s, 3H, CH3); 13C NMR (CDCl3)
d 155.3, 153.4, 150.0, 143.9, 143.2, 138.1, 128.5, 127.7,
127.0, 126.7, 112.2, 93.8, 87.5, 87.2, 65.5, 59.7, 37.9,
28.0, 27.8; IR (KBr) 2922, 1728, 1642, 1462, 1285, 1072,
615 cmꢀ1; LRMS (ESI) m/z 560 [M+H]+; Anal. Calcd for
C34H33N5O3: C, 72.97; H, 5.94; N, 12.51. Found: C,
72.74; H, 5.87; N, 12.81.
Compound 15: UV (CHCl3) lmax 279 nm; 1H NMR (CDCl3)
d 8.17 (s, 1H), 7.89 (s, 1H), 7.22 (m, 15H), 6.41 (d, 1H,
J¼5.0 Hz), 5.93 (m, 2H), 4.56 (s, 1H), 3.29 (t, 2H,
J¼6.2 Hz), 1.99 (t, 2H, J¼6.0 Hz), 1.25 (s, 6H).
4.1.6. (L)-(1R,2S,3S)-1-(2-Hydroxy)ethyl-3-(adenin-9-
yl)-4-cyclopentene-1,2-diol (1). A solution of 14 (59 mg,
0.11 mmol) in a mixture of MeOH (15 mL) and acetyl chlo-
ride (0.2 mL) was stirred at room temperature for 12 h. The
reaction mixture was neutralized with Et3N and evaporated.
The resulting residue was purified by silica gel column chro-
matography (methylene chloride/methanol¼5:1) to give 1
(12 mg, 41%) as a white solid; mp 198.5 ꢁC; [a]D25 ꢀ25.8
(c 0.1, MeOH); UV (CHCl3) lmax 260 nm; 1H NMR
(MeOH-d4) d 8.17 (s, 1H), 8.14 (s, 1H), 6.22 (dd, 1H,
J¼2.4, 6.3 Hz), 6.06 (dd, 1H, J¼1.7, 6.3 Hz), 5.50 (td, 1H,
J¼2.0, 6.4 Hz), 4.28 (d, 1H, J¼6.5 Hz), 3.83 (t, 2H,
J¼6.6 Hz), 1.97 (m, 2H); 13C NMR (MeOH-d4) d 41.8,
59.3, 66.9, 80.9, 82.5, 120.8, 132.4, 139.8, 141.6, 150.9,
15. Naka, T.; Minakawa, N.; Abe, H.; Kaga, D.; Matsuda, A. J. Am.
Chem. Soc. 2000, 122, 7233–7243.