Ring Opening of Nucleoside 1′,2′-Epoxides with Organoaluminum Reagents: Stereoselective Entry to Ribonucleosides Branched at the Anomeric Position

Article abstract of DOI:10.1021/jo030262u

Epoxidation of 3′,5′-O-(di-tert-butylsilylene)-1′ ,2′-unsaturated uridine (11) with dimethyldioxirane proceeded from the α-face to give the 1′,2′-α-epoxide 12. Upon reacting with organoaluminum reagents, the 1′,2′-α-epoxide 12 underwent preferential syn-opening of the epoxide ring to yield the β-anomers of 1′-methyl- (13β), 1′-ethyl- (14β), 1′-isobutyl- (15β), 1′-ethynyl- (16β), 1′-vinyl- (17β), and 1′-phenyl- (18β) uridine derivatives, although the corresponding α-anomers were also formed except for the reaction with triphenylaluminum. It was found, however, that protection of the N ³-position of 11 either with a benzyloxymethyl or benzoyl group led to the exclusive formation of the desired β-anomers. A possible explanation for the observed stereochemical outcome is presented. A similar strategy was found to be applicable to the synthesis of 1′-branched adenosine analogues, which include protected angustmycin C (37).

Full text of DOI:10.1021/jo030262u

Rin g Op en in g of Nu cleosid e 1′,2′-Ep oxid es w ith Or ga n oa lu m in u m
Rea gen ts: Ster eoselective En tr y to Ribon u cleosid es Br a n ch ed a t
th e An om er ic P osition
Kazuhiro Haraguchi,* Yutaka Kubota, and Hiromichi Tanaka
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku,
Tokyo 142-8555, J apan
harakazu@pharm.showa-u.ac.jp
Received August 12, 2003
Epoxidation of 3′,5′-O-(di-tert-butylsilylene)-1′,2′-unsaturated uridine (11) with dimethyldioxirane
proceeded from the R-face to give the 1′,2′-R-epoxide 12. Upon reacting with organoaluminum
reagents, the 1′,2′-R-epoxide 12 underwent preferential syn-opening of the epoxide ring to yield
the â-anomers of 1′-methyl- (13â), 1′-ethyl- (14â), 1′-isobutyl- (15â), 1′-ethynyl- (16â), 1′-vinyl- (17â),
and 1′-phenyl- (18â) uridine derivatives, although the corresponding R-anomers were also formed
except for the reaction with triphenylaluminum. It was found, however, that protection of the N3-
position of 11 either with a benzyloxymethyl or benzoyl group led to the exclusive formation of the
desired â-anomers. A possible explanation for the observed stereochemical outcome is presented.
A similar strategy was found to be applicable to the synthesis of 1′-branched adenosine analogues,
which include protected angustmycin C (37).
In tr od u ction
The unique structure of the antitumor antibiotic an-
gustmycin C (1)1 has stimulated the synthesis of 1′-
branched nucleoside analogues to explore novel nucleo-
side antimetabolites. Available synthetic methods for this
type of analogue2-5 mostly start with the construction of
sugar components, which allow the introduction of vari-
ous nucleobases. There is, however, an inherent limita-
tion in this approach in terms of diversity at the anomeric
substituents.
In this context, we have reported the first example
of anomeric manipulation of uracil nucleosides (Scheme
1),6 which consists of two reaction steps: (1) stereo-
selective bromo-pivaloyloxylation of 1-[3,5-bis-O-(tert-
butyldimethylsilyl)-2-deoxy-D-erythro-pento-1-enofurano-
syl]uracil (2) to give 3 and (2) nucleophilic substitution
of 3 by the use of organosilicon reagents/SnCl4 or orga-
noaluminum reagents. The 1′-branched product 4 has
been converted to the 2′-deoxy (5) and the arabinofura-
nosyl (6) derivatives, but synthesis of the ribofuranosyl
counterparts (7) remained problematic.7
(1) (a) Yu¨ntsen, H.; Yonehara, H.; Ui, H. J . Antibiot., Ser. A 1954,
7, 113-115. (b) Yu¨ntsen, H.; Ohkuma, K.; Ishii, Y. J . Antibiot., Ser. A
1956, 9, 195-201. (c) Schroeder, W.; Hoeksema, H. J . Am. Chem. Soc.
1959, 81, 1767-1768. (d) McCarthy, J . R.; Robins, R. K.; Robins, M.
J . J . Am. Chem. Soc. 1968, 90, 4993-4999.
(2) From D-fructose: (a) Farkas, J .; Sorm, F. Tetrahedron Lett. 1962,
813-814. (b) Farkas, J .; Sorm, F. Collect. Czech. Chem. Commun. 1963,
28, 882-886. (c) Hrebabecky, H.; Farkas, J .; Sorm. F. Collect. Czech.
Chem. Commun. 1972, 37, 2059-2065. (d) Prisbe, E. J .; Smejkal, J .;
Verheyden, J . P. H.; Moffatt, J . G. J . Org. Chem. 1976, 41, 1836-
1846. (e) Grouiller, A.; Chattopadhyaya, J . Acta Chem. Scand. 1984,
B38, 367-373. (f) Elliott, R. D.; Niwas, S.; Riordan, J . M.; Montgomery,
J . A.; Secrist, J . A., III Nucleosides Nucleotides 1992, 11, 97-119. (g)
Holy, A. Nucleic Acids Res. 1974, 1, 289-298. (h) Tatsuoka, T.; Imao,
K.; Suzuki, K. Heterocycles 1986, 24, 617-620. (i) Yoshimura, Y.; Ueda,
T.; Matsuda, A. Tetrahedron Lett. 1991, 32, 4549-4552. (j) Yoshimura,
Y.; Otter, B. A.; Ueda, T.; Matsuda, A. Chem. Pharm. Bull. 1992, 40,
1761-1769.
Although there have been several reports dealing with
the C-glycoside synthesis from 1,2-epoxy sugar deriva-
tives,8,9 this approach has not been investigated in the
field of nucleoside chemistry, despite the anticipated
(3) From 1-deoxy-1-nitro-â-D-ribofuranose: Mahmood, K.; Vasella,
A.; Bernet, B. Helv. Chim. Acta 1991, 74, 1555-1584.
(6) Itoh, Y.; Haraguchi, K.; Tanaka, H.; Gen, E.; Miyasaka, T. J .
Org. Chem. 1995, 60, 656-662.
(4) From D-ribonolactone: (a) Faivre-Buet, V.; Grouiller, A.; Descotes,
G. Nucleosides Nucleotides 1992, 11, 1411-1424. (b) Faivre-Buet, V.;
Grouiller, A.; Descotes, G. Nucleosides Nucleotides 1992, 11, 1651-
1660. (c) Hayakawa, H.; Miyazawa, M.; Tanaka, H.; Miyasaka, T.
Nucleosides Nucleotides 1994, 13, 297-308. (d) Cappellacci, L.; Bar-
boni, G.; Palmieri, M.; Pasqualini, M.; Grifantini, M.; Costa, B.;
Martini, C.; Franchetti, P. J . Med. Chem. 2002, 45, 1196-1202.
(5) From D-ribofuranosyl cyanide: (a) Grouiller, A.; Buet, V.; Uteza,
V.; Descotes, G. Synlett 1993, 221-222. (b) Uteza, V.; Chen, G.-H.;
Tuoi, J . L.-Q.; Descotes, G.; Fenet, B.; Grouiller, A. Tetrahedron 1993,
49, 8579-8588.
(7) Stereoselective methods for the synthesis of ribofuranosyl uracil
nucleosides have recently been reported: (a) Kodama, T.; Shuto, S.;
Nomura, M.; Matsuda, A. Chem. Eur. J . 2001, 7, 2332-2340. (b)
Kodama, T.; Shuto, S.; Ichikawa, S.; Matsuda, A. J . Org. Chem. 2002,
67, 7706-7715.
(8) (a) Collins, P. M.; Ferrier, R. J . Monosaccharides: Their Chem-
istry and Their Roles in Natural Products; J ohn Wiley & Sons:
Chichester, UK, 1995. (b) Postema, M. H. D. C-glycoside Synthesis;
CRC Press: Boca Raton, FL, 1995.
(9) Allwein, S. P.; Cox, J . M.; Howard, B. E.; J ohnson, H. W. B.;
Rainier, J . D. Tetrahedron 2002, 58, 1997-2009.
10.1021/jo030262u CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/24/2004
J . Org. Chem. 2004, 69, 1831-1836
1831

Haraguchi et al.
SCHEME 1
defined regiochemistry of incoming-nucleophiles. In this
article, we describe a novel synthesis of 1′-branched
ribofuranosyl nucleosides by way of ring opening of 1′,2′-
R-epoxy nucleosides with organoaluminum reagents.
Resu lts a n d Discu ssion s
When the 1′,2′-unsaturated uridine protected with the
tert-butyldimethylsilyl (TBDMS) group (2)6 was oxidized
with an acetone solution of dimethyldioxirane (DMDO,
1.2 equiv)10 in CH2Cl2 at -30 °C for 0.5 h, complete
disappearance of the starting material was confirmed by
TLC analysis. Although DMDO oxidation of the 5,6-
double bond of pyrimidine nucleosides has been re-
ported,11 formation of such a product was not observed
under the above conditions throughout the present study.
After evaporation of the solvents, the oxidation product
was dissolved in CH2Cl2 and reacted with Me3Al (3 equiv)
at -30 °C for 4.5 h. From this reaction, only 1-[3,5-bis-
O-TBDMS-1-methyl-R-D-arabinofuranosyl]uracil (8) was
isolated in 44% yield. Evidence for the depicted stereo-
chemistry of 8 was provided by NOE experiment: H-6/
H-4′ (4.6%), CH3-1′/H-3′ (1%), and H-2′/H-4′ (2.7%). Under
similar reaction conditions, the TIPDS (1,1,3,3-tetraiso-
propyl-disiloxane-1,3-diyl)-protected substrate (9)12b gave
the arabinofuranosyl nucleosides 10r (36%) and 10â
(6%). Apart from the stereochemistry of the introduced
SCHEME 2
1′-methyl group, these results suggest that epoxidation
of 2 and 9 had proceeded preferentially, if not exclusively,
from the â-face of the 1-enofuranosyl structure.13
In the case of the DTBS (di-tert-butylsilylene)-protected
1′,2′-unsaturated uridine (11),12b the epoxide 12 obtained
after evaporation of the oxidation mixture was found to
4.5 h,14 12 gave a mixture of 13â and 13r (13â/13r )
5/1) in 86% yield (Scheme 2, entry 1 in Table 1).
1
be fairly stable in CDCl3. Its H NMR spectrum combined
Under similar reaction conditions, the 1′,2′-R-epoxide
12 reacted with a variety of organoaluminum reagents
to give the respective 1′-carbon-substituted products (14-
18) in good yields, except for the synthesis of the
1′-isobutyluridine derivative (15) in which dominant
hydride attack took place to yield 3′,5′-O-(di-tert-butyl-
with NOE studies confirmed that the epoxide 12 was a
single isomer with 1′,2′-R-epoxy stereochemistry, the
observed NOE correlation being 15.4% between H-3′ and
H-6. Upon reacting with Me3Al in CH2Cl2 at -30 °C for
(10) (a) Adam, W.; Hadjiarapoglou, L.; Smerz, A. Chem. Ber. 1991,
124, 227-232. (b) Adam, W.; Bialas, J .; Hadjiarapoglou, L. Chem. Ber.
1991, 124, 2377.
(14) When this reaction was conducted at room temperature, the
combined yield of 13r plus 13â decreased to 55% due to further reaction
of these products with Me3Al to yield an elimination byproduct, 3,5-
O-(di-tert-butylsilylene)-1-methylidene-D-ribofuranose: 1H NMR (CDCl3)
(11) Saladino, R.; Bernini, R.; Crestini, C.; Mincione, E.; Bergamini,
A.; Marini, S.; Palamara, A. T. Tetrahedron 1995, 51, 7561-7578.
(12) (a) Itoh, Y.; Haraguchi, K.; Tanaka, H.; Matsumoto, K.; Naka-
mura, K. T.; Miyasaka, T. Tetrahedron Lett. 1995, 36, 3867-3870. (b)
Haraguchi, K.; Itoh, Y.; Matsumoto, K.; Hashimoto, K.; Nakamura,
K. T.; Tanaka, H. J . Org. Chem. 2003, 68, 2006-2009.
δ 1.01 and 1.04 (18H, each as s), 2.37 (1H, br), 3.93 (1H, dd, J 5′a,5′b
9.2 Hz and J 5′a,4′ ) 10.7 Hz), 4.00 (1H, dd, J 3′,4′ ) 9.2 Hz and J 2′,3′
)
)
4.4 Hz), 4.22 (1H, ddd, J 5′a,4′ ) 10.7 Hz, J 5′b,4′ ) 5.1 Hz, and J 3′,4′ ) 9.2
Hz), 4.36 (1H, d, J gem) 2.2 Hz), 4.43 (1H, dd, J 5′a,5′b ) 9.2 Hz and J 4′,5′b
) 5.1 Hz), 4.46 (1H, d, J 2′,3′ ) 4.4 Hz), 4.50 (1H, d, J gem ) 2.2 Hz);
FAB-MS m/z 287 (M+ + H).
(13) The stereochemistry of epoxides derived from 2 and 9 could not
be determined by NOE experiment due to their instability.
1832 J . Org. Chem., Vol. 69, No. 6, 2004

Ring Opening of Nucleoside 1′,2′-Epoxides
coordination of R3Al to the C2-carbonyl oxygen. This
turned out to be the case. When the N3-benzyloxymethyl
1′,2′-unsaturated uridine 19, prepared from 11, was
oxidized with DMDO and then reacted with Me3Al, 20â
was obtained in 93% yield without any trace amount of
the R-isomer being formed. The exclusive syn-ring open-
ing was also observed in the reaction with Et3Al and
i-Bu3Al to give 21â (75%) and 22â (39%), respectively,
as the sole product. Hydrogenolysis of 20â in the presence
of 5% Pd/C gave 13â in excellent yield.
TABLE 1. Rea ction s of 12 w ith Or ga n oa lu m in u m
Rea gen tsa
entry
R3Al (equiv)
Me3Al (3)
Et3Al (3)
i-Bu3Al (6)
(HCtC)3Al (6)
products
yield (%) ratio of â/R
1
2
3
4
5
6
13â, 13r
14â, 14r
15â, 15r
16â, 16r
86
90
35
64
90
55
5/1
4/1
9/1
4/1
32/1
(H2CdCH)3Al (6) 17â, 17r
Ph3Al (6) 18â
a
All reactions were carried out in CH2Cl2 at -30 °C for 4.5 h.
SCHEME 3
In cases where the 1′-substituents to be introduced are
susceptible to hydrogenation conditions, the N3-benzoy-
lated substrate 23 was used. This substrate was prepared
through benzoylation of 3′,5′-O-(di-tert-butylsilylene)-2′-
deoxy-2′-phenylselenouridine12 and subsequent oxidative
syn elimination. The epoxide derived from 23 again
underwent exclusive syn-ring opening upon reacting with
HCtCAlEt2 (24â, 53%), (H2CdCH)3Al (25â, 75%), and
N3AlEt2 (26b, 52%). Debenzoylation of these products can
be carried out with NH3/MeOH to give the corresponding
N3-deprotected derivatives (16â, 17â, and 27â) in quan-
titative yields.
Finally, we turned our attention to the synthesis of 1′-
substituted adenosines. The substrate 31 for DMDO
oxidation was prepared from 3′,5′-O-DTBS-adenosine
28.15 Thus, treatment of 28 with I2/Ph3P/imidazole in
refluxing dioxane gave 2′-deoxy-2′-iodo-arabinofuranosyl
nucleoside 29 (72%) after acidic hydrolysis of the result-
ing N6-phosphorane.16 Elimination reaction of 29 was
effected with DBN in refluxing CH3CN to give 30 (68%).
To prevent oxidation at the N1-position with DMDO,17
30 was further converted to the N6-pivaloyl derivative
31 (90%).
silylene)uridine (entry 3). Although preferential forma-
tion of the desired syn-ring-opened â-anomers was seen
in entries 1-5, these products were always accompanied
with the respective anti-opened R-anomers, except for
entry 6.
In Scheme 3 is shown a possible reaction pathway for
the reactions listed in Table 1. The epoxide 12, upon
reacting with R3Al, could form an aluminum enolate A
by dissociating acidic N3-H. Coordination of R3Al with
the C2-carbonyl of the base moiety as well as the oxygen
atom of the epoxide ring results in the formation of B,
which in turn forms the oxonium intermediate C. In cases
where nucleophilic attack of the ligand R takes place from
the 2′-O-aluminate (path a), only the syn-ring-opened
products (13â-18â) should result, whereas such attack
of R from the base moiety (path b) would permit the
formation of both anti- and syn-ring-opened products
depending on the conformation about the N1-C1′ pivot
bond.
Epoxidation of 31 with DMDO was carried out under
the same reaction conditions as the case for the 1′,2′-
unsaturated uridine 11. Although no attempt was made
to analyze the diastereomeric purity of the resulting
(15) Furusawa, K.; Ueno, K.; Katsura, T. Chem. Lett. 1990, 97-
100.
On the basis of the above proposed reaction mecha-
nism, we anticipated that the introduction of a sterically
demanding protecting group to the N3-position would lead
to the sole formation of the â-anomer by preventing
(16) Gimisis, T.; Ialongo, G.; Chatgilialoglu, C. Tetrahedron 1998,
54, 573-592.
(17) DMDO oxidation at the base moiety of adenosine derivatives
has been reported: Saladino, R.; Crestini, C.; Bernini, R.; Mincione,
E.; Ciafrino, R. Tetrahedron Lett. 1995, 36, 2665-2668.
J . Org. Chem, Vol. 69, No. 6, 2004 1833

Haraguchi et al.
TABLE 2. Syn th esis of 32â-36â fr om th e Ep oxid e
on silica gel (Silica Gel 60, Merck). Thin-layer chromatography
(TLC) was performed on silica gel (precoated silica gel plate
F254, Merck). HPLC was carried out on a Shimadzu LC-6AD
with a shim-pack PREP-SIL(H)‚KIT column (2 × 25 cm2).
Der ived fr om 31
entry
R3Al (equiv)
Me3Al (3)
Et3Al (3)
i-Bu3Al (6)
(HCtC)3Al (6)
(H2CdCH)3Al (6)
time (h) temp (°C) product yield (%)
1
2
3
4
5
4.5
4.5
4.5
7.0
4.5
-30
32â
33â
34â
35â
36â
80
59
37
39
68
N3-Ben zyloxym eth yl-1-[3,5-O-(d i-ter t-bu tylsilylen e)-2-
deoxy-D-er yth r o-pen to-1-en ofu r an osyl]u r acil (19). A stirred
DMF (30 mL) solution of 11 (500 mg, 1.4 mmol) was treated
with DBU (0.5 mL, 2.8 mmol) and then with benzyloxymethyl
chloride (0.4 mL, 2.8 mmol) at 0 °C. After being stirred for 3.5
h at room temperature, the reaction mixture was partitioned
between EtOAc/H2O. Column chromatography (hexane/EtOAc
) 3/1) of the organic layer gave 19 (614 mg, 93%) as a foam:
-30
-30
-30 to rt
-30
SCHEME 4
1
UV (MeOH) λmax 268 nm (ꢀ 10 000), λmin 247 nm (ꢀ 9 000); H
NMR (CDCl3) δ 0.96 and 0.99 (18H, each as s), 4.10 (1H, dd,
J 4′,5′a ) 11.0 Hz and J 5′a,5′b ) 8.3 Hz), 4.17 (1H, ddd, J 4′,5′a
)
11.0 Hz, J 4′,5′b ) 4.6 Hz, and J 3′,4′ ) 10.4 Hz), 4.40 (1H, dd,
J 5′a,5′b ) 8.3 Hz and J 4′,5′b ) 4.6 Hz), 4.62 (2H, s), 5.23 (1H, dd,
J 3′,4′ ) 10.4 Hz and J 2′,3′ ) 1.7 Hz), 5.42 (2H, s), 5.70 (1H, d,
J 5,6 ) 8.2 Hz), 5.77 (1H, d, J 2′,3′ ) 1.7 Hz), 7.16-7.30 (5H, m),
7.42 (1H, d, J 5,6 ) 8.2 Hz); FAB-MS m/z 487 (M+ + H). Anal.
Calcd for C25H34N2O6Si: C, 61.70; H, 7.04; N, 5.76. Found: C,
61.57; H, 7.18; N, 5.67.
N3-Ben zyloxym et h yl-3′,5′-O-(d i-ter t-b u t ylsilylen e)-1′-
m eth ylu r id in e (20â). This compound was prepared from 19
(50 mg, 0.1 mmol) through DMDO oxidation followed by the
reaction with Me3Al (6 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography (hexane/EtOAc ) 3/1) of the
organic layer gave 20â (49.8 mg, 93%, foam): UV (MeOH) λmax
267 nm (ꢀ 9400), λmin 234 nm (ꢀ 1500); 1H NMR (CDCl3) δ 1.03
and 1.05 (18H, each as s), 1.75 (3H, s), 2.57 (1H, br), 3.76 (1H,
epoxide, its reaction with Me3Al gave the 1′-methyl-
adenosine derivative 32â in 80% yield (entry 1 in Table
2). Under similar reaction conditions, Et3Al, i-Bu3Al,
(HCtC)3Al, and (H2CdCH)3Al also effected the stereo-
selective C-C bond formation at the anomeric position
to give 33â-36â (entries 2-5). No formation of the
dd, J 3′,4′ ) 9.0 Hz and J 2′,3′ ) 4.6 Hz), 3.93 (1H, dd, J 5′a,5′b
)
9.0 Hz and J 4′,5′a ) 10.4 Hz), 4.12 (1H, ddd, J 4′,5′a ) 10.4 Hz,
J 4′,5′b ) 5.1 Hz, and J 3′,4′ ) 9.0 Hz), 4.48 (1H, dd, J 5′a,5′b ) 9.0
Hz and J 4′,5′b ) 5.1 Hz), 4.66 (1H, d, J 2′,3′ ) 4.6 Hz), 4.73 (2H,
s), 5.48 (2H, s), 5.70 (1H, d, J 5,6 ) 8.4 Hz), 7.23-7.37 (5H, m),
7.64 (1H, d, J 5,6 ) 8.4 Hz); NOE experiment, CH3-1′/H-4′(1.8%),
H-6/H-5′a (1.6%), H-6/H-3′ (2.4%); FAB-MS m/z 520 (M+ + H).
Anal. Calcd for C26H38N2O7Si: C, 60.21; H, 7.38; N, 5.40.
Found: C, 60.21; H, 7.54; N, 5.14.
corresponding R-anomers was observed throughout these
reactions. The 1′-vinyl derivative 36â could be trans-
formed to protected angustmycin C (37) through oxidative
cleavage of the double bond with OsO4/NaIO4, hydride
reduction of the resulting aldehyde, and acetylation of
the diol. This is the first example that protected angust-
mycin C was synthesized from adenosine. In conclusion,
we have developed a novel method for the synthesis of
ribofuranosyl nucleosides having a carbon substituent at
the anomeric position by way of nucleophilic ring opening
of 1′,2′-epoxy nucleoside with aluminum reagents. The
epoxides were prepared by DMDO oxidation of 3′,5′-O-
DTBS-protected 1′, 2′-unsaturated nucleosides. Although
nucleophilic ring opening of the 1′,2′-R-epoxyuridine
derivative 12 gave a mixture of â- and R-anomers,
benzyloxymethyl or benzoyl protection at the N3-position
completely suppressed the formation of the R-anomer.
This synthetic method enabled us to introduce a variety
of carbon substituents as well as an azido group at the
amomeric position of uridine. A similar approach was
successfully adopted to 3′,5′-O-DTBS-protected 1′,2′-
unsaturated N6-pivaloyladenosine 31. Evaluation of the
biological activities of deprotected 1′-branched nucleoside
analogues is in progress.
N3-Ben zyloxym et h yl-3′,5′-O-(d i-ter t-b u t ylsilylen e)-1′-
eth ylu r id in e (21â). This compound was prepared from 19 (50
mg, 0.1 mmol) through DMDO oxidation followed by the
reaction with Et3Al (3 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 3/1) gave 21â (40.9 mg, 75%, foam): UV (MeOH) λmax
267 nm (ꢀ 9100), λmin 234 nm (ꢀ 1200); 1H NMR (CDCl3) δ 0.71
(3H, t, J ) 7.5 Hz), 1.03 and 1.05 (18H, each as s), 2.00 (1H,
dt, J ) 7.5 Hz and J gem ) 7.3 Hz), 2.52 (1H, br), 2.63 (1H, dt,
J ) 7.5 Hz and J gem ) 7.3 Hz), 3.77 (1H, dd, J 3′,4′ ) 9.7 Hz and
J 2′,3′ ) 4.8 Hz), 3.95 (1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′a ) 10.6
Hz), 4.09 (1H, ddd, J 4′,5′a ) 10.6 Hz, J 4′,5′b ) 4.9 Hz, and J 3′,4′
)
9.7 Hz), 4.49 (1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′b ) 4.9 Hz), 4.68
(1H, d, J 2′,3′ ) 4.8 Hz), 4.72 (2H, s), 5.49 (2H, s), 5.69 (1H, d,
J 5,6 ) 8.4 Hz), 7.24-7.38 (5H, m), 7.60 (1H, d, J 5,6 ) 8.4 Hz);
NOE experiment, CH3CH2a-1′/H-4′ (4.4%), H-6/H-5′a (4.9%),
H-6/H-3′ (3.7%); FAB-MS m/z 533 (M+ + H). Anal. Calcd for
C
27H40N2O7Si‚1/10H2O: C, 60.67; H, 7.58; N, 5.24. Found: C,
60.77; H, 7.67; N, 4.95.
N3-Ben zyloxym et h yl-3′,5′-O-(d i-ter t-b u t ylsilylen e)-1′-
isobu tylu r id in e (22â). This compound was prepared from 19
(50 mg, 0.1 mmol) through DMDO oxidation followed by the
reaction with i-Bu3Al (6 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 3/1) gave 22â (22.3 mg, 39%, foam): UV (MeOH) λmax
Exp er im en ta l Section
1
Melting points are uncorrected. H NMR was measured at
400 or 500 MHz. Chemical shifts are reported relative to Me4-
Si. Mass spectra (MS) were taken in FAB mode (m-nitrobenzyl
alcohol as a matrix). Column chromatography was carried out
1
267 nm (ꢀ 10 500), λmin 236 nm (ꢀ 4 000); H NMR (CDCl3) δ
0.79 (3H, d, J ) 6.6 Hz), 0.90 (3H, d, J ) 6.8 Hz), 1.03 and
1834 J . Org. Chem., Vol. 69, No. 6, 2004

Ring Opening of Nucleoside 1′,2′-Epoxides
1.05 (18H, each as s), 1.47 (1H, m), 1.81 (1H, dd, J ) 7.0 Hz
and J gem ) 15.2 Hz), 2.46 (1H, br), 2.65 (1H, dd, J ) 5.3 Hz
0.16 mmol) through DMDO oxidation followed by the reaction
with trivinylaluminum (6 equiv). The procedures employed
were essentially the same as those described for the prepara-
tion of 8 from 2. The Celite filtrate was partitioned between
CHCl3/H2O. Column chromatography of the organic layer
(hexane/EtOAc ) 4/1) gave 25â (61.5 mg, 75%, foam): UV
(MeOH) λmax 254 nm (ꢀ 20 800), λmin 226 nm (ꢀ 6 100); 1H NMR
(CDCl3) δ 1.01 and 1.08 (18H, each as s), 2.57 (1H, br), 3.96
(1H, dd, J 3′,4′ ) 9.6 Hz and J 2′,3′ ) 4.6 Hz), 4.03 (1H, dd, J 5′a,5′b
) 9.0 Hz and J 4′,5′a ) 10.6 Hz), 4.16 (1H, ddd, J 4′,5′a ) 10.6 Hz,
J 4′,5′b ) 4.9 Hz, and J 3′,4′ ) 9.6 Hz), 4.56 (1H, dd, J 5′a,5′b ) 9.0
Hz and J 4′,5′b ) 4.9 Hz), 4.90 (1H, d, J 2′,3′ ) 4.6 Hz), 5.46 (1H,
and J gem ) 15.2 Hz), 3.75 (1H, dd, J 3′,4′ ) 9.6 Hz and J 2′,3′
)
4.4 Hz), 3.95 (1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′a ) 10.3 Hz),
4.12 (1H, ddd, J 4′,5′a ) 10.3 Hz, J 4′,5′b ) 4.9 Hz, and J 3′,4′ ) 9.6
Hz), 4.50 (1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′b ) 4.9 Hz), 4.61
(1H, d, J 2′,3′ ) 4.4 Hz), 4.70 (2H, s), 5.49 (2H, s), 5.72 (1H, d,
J 5,6 ) 8.4 Hz), 7.26-7.37 (5H, m), 7.66 (1H, d, J 5,6 ) 8.4 Hz);
NOE experiment, CH3CH2a-1′/H-4′ (1.9%), H-6/H-5′a (5.1%),
H-6/H-3′ (2.1%); FAB-MS m/z 561 (M+ + H). Anal. Calcd for
C29H44N2O7Si‚1/10H2O: C, 61.92; H, 7.92; N, 4.98. Found: C,
61.81; H, 8.05; N, 4.72.
Hyd r ogen olysis of 20â To Yield 13â. A mixture of 20â
(43 mg, 0.08 mmol) and 5% Pd/C (15 mg) in MeOH (4 mL)
was stirred at room temperature for 6 h under positive
pressure of H2. Removal of the catalyst by filtration was
followed by evaporation of the solvent. This gave 13â (33 mg,
100%), which was identical by 1H NMR spectroscopy with that
prepared from 12.
dd, J CH
) 10.8 and J gem ) 1.1 Hz), 5.58 (1H, dd, J CH
adCH
bdCH
2
) 17.2 Hz and J gem ) 1.1 Hz), 5.81 (1H, d, J 5,6 ) 8.5 Hz),26.54
(1H, dd, J CH
) 17.2 and 10.8 Hz), 7.48-7.68 and 7.89-
dCH
2
7.91 (5H, m), 7.78 (1H, d, J 5,6 ) 8.5 Hz); NOE experiment,
CH2dCH-1′/H-4′ (0.9%), H-6/H-5′a (2.9%); FAB-MS m/z 516
(M+ + H). Anal. Calcd for C26H34N2O7Si: C, 60.68; H, 6.66; N,
5.44. Found: C, 60.49; H, 6.64; N, 5.40.
N3-Ben zoyl-1-[3,5-O-(d i-ter t-b u t ylsilylen e)-2-d eoxy-D-
er yth r o-p en t o-1-en ofu r a n osyl]u r a cil (23). To a mixture
of 3′,5′-O-(di-tert-butylsilylene-2′-deoxy-2′-phenylselenouridine12b
(1.25 g, 2.4 mmol) and i-Pr2NEt (2.5 mL, 14.3 mmol) in CH2-
Cl2 (50 mL) was added benzoyl chloride (1.7 mL, 14.3 mmol)
at 0 °C. After being stirred for 2 h at room temperature, the
reaction mixture was partitioned between CH2Cl2 and sat.
aqueous NaHCO3. Column chromatography (hexane/EtOAc )
5/1) of the organic layer gave the N3-benzoyl derivative (1.38
g, 92%) as a pale yellow foam. Oxidation of this product (937
mg, 1.49 mmol) was carried out by reacting it with m-CPBA
(468 mg, 2.09 mmol) in CH2Cl2 (5 mL) at 0 °C for 2 h.
Neutralization of the oxidation mixture with Et3N was followed
by partition between CH2Cl2/sat. aqueous NaHCO3. Column
chromatography (hexane/EtOAc ) 1/3) of the organic layer
gave the corresponding selenoxide (896 mg, 93%, foam).
Compound 23 (338 mg, 56%, foam) was formed by heating the
above selenoxide (825 mg, 1.28 mmol) in THF (15 mL)
containing Et3N (0.72 mL, 5.13 mmol) at 50 °C for 4 h.
Isolation of 23 was carried out by column chromatography
(hexane/EtOAc ) 5/1).
P r ep a r a tion of Tr ivin yla lu m in u m (0.25 M Solu tion ).
To a stirred CH2Cl2 (16.7 mL) solution of AlCl3 (1.0 g, 7.5
mmol) was added vinylmagnesium chloride (1.7 M in THF
solution) at 0 °C under Ar atmosphere and the mixture was
stirred overnight. The resulting solution was used for the
vinylation reaction.
1′-Azid o-N 3-b e n zoyl-3′,5′-O-(d i-t er t -b u t ylsilyle n e )-
u r id in e (26â). This compound was prepared from 23 (75 mg,
0.16 mmol) through DMDO oxidation followed by the reaction
with N3AlEt2 (toluene solution, 3 equiv). The procedures
employed were essentially the same as those described for the
preparation of 8 from 2. The Celite filtrate was partitioned
between CHCl3/H2O. Column chromatography of the organic
layer (hexane/EtOAc ) 4/1) gave 26â (44.2 mg, 52%, foam):
1H NMR (CDCl3) δ 1.04 and 1.07 (18H, each as s), 2.95 (1H,
br), 3.97 (1H, dd, J 3′,4′ ) 9.8 Hz and J 2′,3′ ) 4.8 Hz), 3.99 (1H,
dd, J 5′a,5′b ) 9.1 Hz and J 4′,5′a ) 10.7 Hz), 4.43 (1H, ddd, J 4′,5′a
) 10.7 Hz, J 4′,5′b ) 5.1 Hz, and J 3′,4′ ) 9.8 Hz), 4.57 (1H, dd,
J 5′a,5′b ) 9.1 Hz and J 4′,5′b ) 5.1 Hz), 4.97 (1H, d, J 2′,3′ ) 4.8
Hz), 5.84 (1H, d, J 5,6 ) 8.4 Hz), 7.49-7.69 and 7.90-7.93 (5H,
m), 7.77 (1H, d, J 5,6 ) 8.4 Hz); 13C NMR (CDCl3) δ 20.44, 22.72,
27.03, 27.24, 66.66, 75.23, 75.63, 75.95, 102.60, 105.91, 129.28,
130.47, 131.10, 135.36, 137.76, 148.71, 161.59, 168.08; NOE
experiment, 2′-OH/H-4′ (1.1%), H-6/H-5′a (3.8%), H-6/H-3′
(2.8%); FAB-HRMS m/z calcd for C24H32N5O7Si 530.2071, found
Physical data for 23: foam; 1H NMR (CDCl3) δ 1.03 and
1.05 (18H, each as s), 4.19 (1H, dd, J 4′,5′a ) 11.0 Hz and J 5′a,5′b
) 8.3 Hz), 4.26 (1H, ddd, J 4′,5′a ) 11.0 Hz, J 4′,5′b ) 4.6 Hz, and
J 3′,4′ ) 10.8 Hz), 4.50 (1H, dd, J 5′a,5′b ) 8.3 Hz and J 4′,5′b ) 4.6
Hz), 5.30 (1H, dd, J 3′,4′ ) 10.8 Hz and J 2′,3′ ) 1.7 Hz), 5.82 (1H,
d, J 2′,3′ ) 1.7 Hz), 5.89 (1H, d, J 5,6 ) 8.4 Hz), 7.49-7.93 (5H,
m), 7.93 (1H, d, J 5,6 ) 8.4 Hz); 13C NMR (CDCl3) δ 20.24, 22.52,
27.19, 27.42, 66.50, 79.70, 82.56, 96.46, 102.88, 129.22, 130.47,
131.08, 135.30, 138.75, 145.03, 146.03, 146.97, 161.04, 167.84;
530.2108 (M+ + H); IR (neat) 2136 cm-1
.
1′-Azid o-3′,5′-O-(di-ter t-bu tylsilylen e)u r id in e (27â): De-
ben zoyla tion of 26â a s a Typ ica l P r oced u r e. Compound
26â (28 mg) in NH3/MeOH (7 mL) was stirred for 1 h at room
temperature. Evaporation followed by column chromatography
(hexane/EtOAc ) 2/1) of the reaction mixture gave 27â (22
mg, 100%, foam): 1H NMR (CDCl3) δ 1.05 (18H, each as s),
3.91 (1H, dd, J 3′,4′ ) 9.7 Hz and J 2′,3′ ) 4.7 Hz), 3.96 (1H, dd,
J 5′a,5′b ) 9.0 Hz and J 4′,5′a ) 10.3 Hz), 4.34 (1H, br), 4.57 (1H,
FAB-HRMS m/z calcd for
C24H31N2O6Si 471.1951, found
471.1992 (M+ + H).
N3-Ben zoyl-3′,5′-O-(d i-ter t-b u t ylsilylen e)-1′-et h yn yl-
u r id in e (24â). This compound was prepared from 23 (50 mg,
0.11 mmol) through DMDO oxidation followed by the reaction
with HCtCAlEt2 (6 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 5/1) gave 24â (28.9 mg, 53%, foam): 1H NMR (CDCl3)
δ 1.03 and 1.06 (18H, each as s), 2.88 (1H, s), 3.02 (1H, br),
3.97 (1H, dd, J 3′,4′ ) 9.7 Hz and J 2′,3′ ) 4.8 Hz), 4.00 (1H, dd,
dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′b ) 5.1 Hz), 4.49 (1H, ddd, J 4′,5′a
)
10.3 Hz, J 4′,5′b ) 5.1 Hz, and J 3′,4′ ) 9.7 Hz), 4.77 (1H, d, J 2′,3′
) 4.7 Hz), 5.77 (1H, d, J 5,6 ) 8.3 Hz), 7.70 (1H, d, J 5,6 ) 8.3
Hz), 9.65 (1H, br); 13C NMR (CDCl3) δ 22.40, 22.73, 27.06,
27.30, 66.99, 74.93, 75.50, 75.63, 102.03, 106.16, 139.14,
150.05, 163.34; NOE experiment, H-6/H-3′ (0.9%), H-6/H-5′a
(3.8%); FAB-HRMS m/z calcd for C17H28N5O6Si 426.1809, found
426.1821 (M+ + H); IR (neat) 2123 cm-1
.
3′,5′-O-(Di-ter t-b u t ylsilylen e)-1′-m et h yl-N6-p iva loyl-
a d en osin e (32â). This compound was prepared from 31 (50
mg, 0.11 mmol) through DMDO oxidation followed by the
reaction with Me3Al (3 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 2/1) gave 32â (42.5 mg, 80%, foam): 1H NMR (CDCl3)
δ 0.99 and 1.03 (18H, each as s), 1.41 (9H, s), 1.95 (3H, s),
3.26 (1H, br), 3.98 (1H, dd, J 3′,4′ ) 9.5 Hz and J 2′,3′ ) 4.2 Hz),
4.02 (1H, dd, J 5′a,5′b ) 9.2 Hz and J 4′,5′a ) 10.4 Hz), 4.29 (1H,
J 5′a,5′b ) 9.2 Hz and J 4′,5′a ) 10.2 Hz), 4.13 (1H, ddd, J 4′,5′a
)
10.2 Hz, J 4′,5′b ) 5.1 Hz, and J 3′,4′ ) 9.7 Hz), 4.53 (1H, dd, J 5′a,5′b
) 9.2 Hz and J 4′,5′b ) 5.1 Hz), 4.71 (1H, d, J 2′,3′ ) 4.8 Hz), 5.86
(1H, d, J 5,6 ) 8.4 Hz), 7.48-7.68 and 7.91-7.93 (5H, m), 7.82
(1H, d, J 5,6 ) 8.4 Hz); 13C NMR (CDCl3) δ 20.39, 22.71, 27.08,
27.28, 66.86, 74.93, 75.04, 76.40, 78.27, 93.66, 102.29, 129.23,
130.50, 130.55, 131.24, 135.29, 138.07, 148.63, 161.76, 168.20;
FAB-HRMS m/z calcd for
C26H33N2O7Si 513.2057, found
513.2064 (M+ + H).
N 3-B e n zo y l-3′,5′-O -(d i-t er t -b u t y ls ily le n e )-1′-v in y l-
u r id in e (25â). This compound was prepared from 23 (75 mg,
J . Org. Chem, Vol. 69, No. 6, 2004 1835

Haraguchi et al.
ddd, J 4′,5′a ) 10.4 Hz, J 4′,5′b ) 5.1 Hz, and J 3′,4′ ) 9.5 Hz), 4.56
(1H, dd, J 5′a,5′b ) 9.2 Hz and J 4′,5′b) 5.1 Hz), 4.93 (1H, d, J 2′,3′
) 4.2 Hz), 8.23 (1H, s), 8.51 (1H, br), 8.74 (1H, s); 13C NMR
(CDCl3) δ 20.26, 22.17, 22.52, 27.18, 27.31, 40.33, 67.55, 73.72,
74.58, 76.28, 98.49, 124.39, 140.36, 149.53, 150.14, 152.10,
175.68; NOE experiment, 2′-OH/H-4′ (1.3%), CH3-1′/H-4′ (1.2%),
H-2/H-5′a (2.8%); FAB-HRMS m/z calcd for C24H40N5O5Si
506.2799, found 506.2834 (M+ + H).
150.31, 152.58, 175.63; NOE experiment, H-3′/H-2 (1.6%), H-2/
H-5′a (2.7%), H-2/H-2′ (0.5%); FAB-HRMS m/z calcd for
C25H38N5O5Si 516.2642, found 516.2594 (M+ + H).
3′,5′-O -(D i-t er t -b u t y ls ily le n e )-N 6-p iv a lo y -1′-v in y l-
a d en osin e (36â). This compound was prepared from 31 (36
mg, 0.08 mmol) through DMDO oxidation followed by the
reaction with trivinylaluminum (5 equiv). The procedures
employed were essentially the same as those described for the
preparation of 8 from 2. The Celite filtrate was partitioned
between CHCl3/H2O. Column chromatography of the organic
layer (hexane/EtOAc ) 1.5/1) gave 36â (22.4 mg, 68%, foam):
3′,5′-O-(Di-t er t -b u t ylsilyle n e )-1′-e t h yl-N 6-p iva loyl-
a d en osin e (33â). This compound was prepared from 31 (50
mg, 0.11 mmol) through DMDO oxidation followed by the
reaction with Et3Al (3 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 2/1) gave 33â (32.3 mg, 59%, foam): 1H NMR (CDCl3)
δ 0.58 (3H, t, J ) 7.4 Hz), 0.98 and 1.03 (18H, each as s), 1.41
(9H, s), 2.30 (1H, dt, J ) 7.4 Hz and J gem ) 7.3 Hz), 2.62 (1H,
dt, J ) 7.4 Hz and J gem ) 7.3 Hz), 2.99 (1H, br), 3.94 (1H, dd,
J 3′,4′ ) 9.7 Hz and J 2′,3′ ) 4.4 Hz), 4.01 (1H, dd, J 5′a,5′b ) 9.2 Hz
1
UV (MeOH) λmax 273 nm (ꢀ 18 200), λmin 235 nm (ꢀ 5 800); H
NMR (CDCl3) δ 1.01 and 1.03 (18H, each as s), 1.40 (9H, s),
2.95 (1H, br), 4.03 (1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′a ) 10.4
Hz), 4.19 (1H, dd, J 3′,4′ ) 9.7 Hz and J 2′,3′ ) 4.2 Hz), 4.29 (1H,
ddd, J 4′,5′a ) 10.4 Hz, J 4′,5′b ) 4.9 Hz, and J 3′,4′ ) 9.7 Hz), 4.59
(1H, dd, J 5′a,5′b ) 9.0 Hz and J 4′,5′b ) 4.9 Hz), 5.27 (1H, d, J 2′,3′
) 4.2 Hz), 5.37 (1H, dd, J ) 17.1 Hz and J gem ) 0.8 Hz), 5.43
(1H, dd, J ) 10.7 Hz and J gem ) 0.8 Hz), 6.58 (1H, dd, J )
17.1 Hz and 10.7 Hz), 8.20 (1H, s), 8.49 (1H, s), 8.74 (1H, s);
NOE experiment, 2′-OH/H-4′ (2.8%), H-2/H-5′a (2.2%), H-2/
H-3′ (1.0%); FAB-MS m/z 518 (M+ + H). Anal. Calcd for
and J 4′,5′a ) 10.6 Hz), 4.25 (1H, ddd, J 4′,5′a ) 10.6 Hz, J 4′,5′b
)
5.1 Hz, and J 3′,4′ ) 9.7 Hz), 4.57 (1H, dd, J 5′a,5′b ) 9.2 Hz and
J 4′,5′b ) 5.1 Hz), 5.01 (1H, d, J 2′,3′ ) 4.4 Hz), 8.20 (1H, s), 8.51
(1H, s), 8.74 (1H, s); 13C NMR (CDCl3) δ 5.78, 20.36, 22.61,
25.98, 27.19, 27.24, 27.41, 40.44, 67.72, 74.01, 74.58, 76.21,
100.59, 124.27, 141.41, 150.14, 152.29, 175.70; NOE experi-
ment, 2′-OH/H-4′ (1.3%), H-2/H-5′a (1.7%), H-2/H-3′ (1.0%);
C
25H39N5O5Si: C, 57.60; H, 7.61; N, 13.45. Found: C, 57.78;
H, 7.78; N, 13.19.
9-[1,3-Di-O-a cetyl-4,6-O-(d i-ter t-bu tylsilylen e)-â-D-p si-
cofu r a n osyl]-N6-p iva loyla d en in e (37). To a stirred 75%
dioxane (5 mL) solution of 36â (53.5 mg, 0.10 mmol) and NaIO4
(110.6 mg, 0.52 mmol) was added a 2% OsO4 solution (0.13
mL, 0.01 mmol) and the mixture was stirred for 4 h at room
temperature. After the reaction mixture was evaporated to
dryness, NaBH4 (3.9 mg, 0,10 mmol) was added to a stirred
EtOH (5 mL) solution of the residue and the mixture was
stirred for 30 min. The reaction mixture was filtered through
Celite and the filtrate was partitioned between AcOEt/sat.
NaCl and the organic layer was purified by preparative TLC
(CHCl3/MeOH ) 12/1) to give the diol. To a stirred pyridine
(2 mL) solution of the diol was added Ac2O (0.03 mL) at 0 °C
and the mixture was stirred at room temperature for 9 h. The
reaction mixture was partitioned between AcOEt/sat. NaHCO3
and silica gel column chromatography (CHCl3/MeOH ) 40/1)
of the organic layer gave 37 (17.1 mg, 27%) as a foam: 1H NMR
(CDCl3) δ 0.96 and 1.00 (18H, each as s), 1.41 (9H, s), 1.87
and 2.25 (6H, each as s), 4.01 (1H, dd, J 5′a,5′b ) 9.4 Hz and
J 4′,5′a ) 10.3 Hz), 4.06 (1H, dd, J 3′,4′ ) 9.9 Hz and J 2′,3′ ) 4.4
FAB-HRMS m/z calcd for
C25H42N5O5Si 520.2955, found
520.2979 (M+ + H).
3′,5′-O-(Di-ter t-b u t ylsilylen e)-1′-isob u t yl-N6-p iva loyl-
a d en osin e (34â). This compound was prepared from 31 (50
mg, 0.11 mmol) through DMDO oxidation followed by the
reaction with i-Bu3Al (3 equiv). The procedures employed were
essentially the same as those described for the preparation of
8 from 2. The Celite filtrate was partitioned between CHCl3/
H2O. Column chromatography of the organic layer (hexane/
EtOAc ) 3/1) gave 34â (21.6 mg, 37%, foam): UV (MeOH) λmax
1
274 nm (ꢀ 19 000),λmin 236 nm (ꢀ 5 900); H NMR (CDCl3) δ
0.49 (3H, d, J ) 6.6 Hz), 0.90 (3H, d, J ) 6.6 Hz), 0.98 and
1.04 (18H, each as s), 1.19 (1H, m), 1.41 (9H, s), 2.13 (1H, dd,
J ) 7.5 Hz and J gem ) 15.2 Hz), 2.65 (1H, dd, J ) 4.8 Hz and
J gem ) 15.2 Hz), 2.81 (1H, br), 3.89 (1H, dd, J 3′,4′ ) 9.8 Hz and
J 2′,3′ ) 4.3 Hz), 4.01 (1H, dd, J 5′a,5′b ) 9.1 Hz and J 4′,5′a ) 10.5
Hz), 4.27 (1H, ddd, J 4′,5′a ) 10.5 Hz, J 4′,5′b ) 4.9 Hz, and J 3′,4′
)
9.8 Hz), 4.56 (1H, dd, J 5′a,5′b ) 9.1 Hz and J 4′,5′b ) 4.9 Hz), 4.84
(1H, d, J 2′,3′ ) 4.3 Hz), 8.18 (1H, s), 8.50 (1H, br), 8.76 (1H, s);
NOE experiment, 2′-OH/H-4′ (1.5%), H-2/H-5′a (1.9%), H-6/
H-3′ (1.0%); FAB-MS m/z 548 (M+ + H). Anal. Calcd for
Hz), 4.25 (1H, ddd, J 4′,5′a ) 10.3 Hz, J 4′,5′b ) 4.9 Hz, and J 3′,4′ )
9.9 Hz), 4.58 (1H, dd, J 5′a,5′b ) 9.4 Hz and J 4′,5′b ) 4.9 Hz), 4.79
(2H, s), 6.57 (1H, d, J 2′,3′ ) 4.4 Hz), 8.19 (1H, s), 8.48 (1H, br),
8.74 (1H, s); 13C NMR (CDCl3) δ 20.31, 20.54, 20.76, 22.70,
27.05, 27.20, 27.53, 40.46, 62.88, 67.37, 73.85, 75.02, 75.43,
95.68, 124.00, 140.76, 149.47, 150.49, 152.54, 168.03, 169.75,
175.52; FAB-HRMS m/z calcd for C28H44N5O8Si 606.2959,
found 606.2949 (M+ + H).
C
27H45N5O5Si‚1/3H2O: C, 58.56; H, 8.31; N, 12.65. Found: C,
58.74; H, 8.47; N, 12.42.
3′,5′-O-(Di-ter t-b u t ylsilylen e)-1′-et h yn yl-N6-p iva loyl-
a d en osin e (35â). This compound was prepared from 31 (80
mg, 0.17 mmol) through DMDO oxidation followed by the
reaction with triethynylaluminum (5 equiv). The procedures
employed were essentially the same as those described for the
preparation of 8 from 2. The Celite filtrate was partitioned
between CHCl3/H2O. Column chromatography of the organic
layer (hexane/EtOAc ) 2/1) gave 35â (51.3 mg, 59%, foam):
1H NMR (CDCl3) δ 1.06 (18H, each as s), 1.40 (9H, s), 3.06
(1H, s), 3.67 (1H, br), 4.05 (1H, dd, J 5′a,5′b ) 9.2 Hz and J 4′,5′a
) 10.4 Hz), 4.35 (1H, ddd, J 4′,5′a ) 10.4 Hz, J 4′,5′b ) 5.1 Hz,
Ack n ow led gm en t. Financial support from the J a-
pan Society for the Promotion of Science (KAKENHI:
No.15590100 to K.H.; No. 15590020 to H.T.), the J apan
Health Sciences Foundation (SA14718 to H.T.), and the
Research Foundation for Pharmaceutical Sciences (to
K.H.) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and full characterization for compounds 8-18b and
29-31. This material is available free of charge via the
Internet at http://pubs.acs.org.
and J 3′,4′ ) 9.6 Hz), 4.52 (1H, dd, J 5′a,5′b ) 9.2 Hz and J 4′,5′b
)
5.1 Hz), 4.58 (1H, dd, J 3′,4′ ) 9.6 Hz and J 2′,3′ ) 4.9 Hz), 5.12
(1H, d, J 2′,3′ ) 4.9 Hz), 8.40 (1H, s), 8.49 (1H, br), 8.76 (1H, s);
13C NMR (CDCl3) δ 20.37, 22.67, 27.15, 27.27, 27.40, 40.49,
67.07, 74.94, 75.52, 76.46, 79.57, 92.03, 124.20, 140.86, 149.82,
J O030262U
1836 J . Org. Chem., Vol. 69, No. 6, 2004