Stereo- And Regioselective Introduction of 1- or 2-Hydroxyethyl Group via Intramolecular Radical Cyclization Reaction with a Novel Silicon-Containing Tether. An Efficient Synthesis of 4′α-Branched 2′-Deoxyadenosines

Article abstract of DOI:10.1021/jo971703a

An efficient method for the synthesis of 4′α-branched 2′-deoxyadenosines starting from 2′-deoxyadenosine has been developed utilizing a novel radical cyclization reaction with a silicon tether. The radical reaction of 4′β-(phenylseleno)-3′-O-diphenylvinylsilyl adeninenucleoside derivative 17 with Bu₃SnH and AIBN, followed by Tamao oxidation, gave selectively either the 4′α-(2-hydroxyethyl) derivative 21 or 4′α-(1-hydroxyethyl) derivative 19, depending on the reaction conditions. With a lower Bu₃SnH concentration, the reaction gave the 4′α-(2-hydroxyethyl) derivative 21, via a 6-endo-radical cyclized product 20, as the sole product in 72% yield. The reaction of 17 in the presence of excess Bu₃SnH gave 19 quantitatively, via a 5-exo-cyclized product 18, as a diastereomeric mixture. The reaction mechanism was examined using Bu₃SnD. The results demonstrated that the 5-exo cyclized (3-oxa-2-silacyclopentyl)methyl radical (C) was formed initially which was trapped when the concentration of Bu₃SnH(D) was high enough. With lower concentrations of Bu₃SnHCD), radical C rearranged into the ring-enlarged 4-oxa-3-silacyclohexyl radical (D) which was then trapped with Bu₃SnH(D) to give endo-cyclized product F.

Full text of DOI:10.1021/jo971703a

746
J . Org. Chem. 1998, 63, 746-754
Ster eo- a n d Regioselective In tr od u ction of 1- or 2-Hyd r oxyeth yl
Gr ou p via In tr a m olecu la r Ra d ica l Cycliza tion Rea ction w ith a
Novel Silicon -Con ta in in g Teth er . An Efficien t Syn th esis of
4′r-Br a n ch ed 2′-Deoxya d en osin es1
Satoshi Shuto,* Makiko Kanazaki, Satoshi Ichikawa, Noriaki Minakawa, and
Akira Matsuda*
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060, J apan
Received September 12, 1997
An efficient method for the synthesis of 4′R-branched 2′-deoxyadenosines starting from 2′-
deoxyadenosine has been developed utilizing a novel radical cyclization reaction with a silicon tether.
The radical reaction of 4′â-(phenylseleno)-3′-O-diphenylvinylsilyl adeninenucleoside derivative 17
with Bu3SnH and AIBN, followed by Tamao oxidation, gave selectively either the 4′R-(2-
hydroxyethyl) derivative 21 or 4′R-(1-hydroxyethyl) derivative 19, depending on the reaction
conditions. With a lower Bu3SnH concentration, the reaction gave the 4′R-(2-hydroxyethyl)
derivative 21, via a 6-endo-radical cyclized product 20, as the sole product in 72% yield. The reaction
of 17 in the presence of excess Bu3SnH gave 19 quantitatively, via a 5-exo-cyclized product 18, as
a diastereomeric mixture. The reaction mechanism was examined using Bu3SnD. The results
demonstrated that the 5-exo cyclized (3-oxa-2-silacyclopentyl)methyl radical (C) was formed initially
which was trapped when the concentration of Bu3SnH(D) was high enough. With lower
concentrations of Bu3SnH(D), radical C rearranged into the ring-enlarged 4-oxa-3-silacyclohexyl
radical (D) which was then trapped with Bu3SnH(D) to give endo-cyclized product F .
In tr od u ction
Considerable attention has been focused on branched-
chain sugar nucleosides because of their biological
importance.2-10 We have developed stereoselective syn-
thetic methods for 2′- and 3′-branched-chain sugar nu-
cleosides and have prepared a variety of 2′- and 3′-
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F igu r e 1.
modified nucleoside analogues.5,6 We found that 1-(2-
deoxy-2-methylene-â-D-erythro-pentofuranosyl)cytosine
(DMDC, 1),5s-v 1-(2-C-cyano-2-deoxy-â-D-arabino-pento-
furanosyl)cytosine (CNDAC, 2),5w-z and 1-(3-C-ethynyl-
â-D-ribo-pentofuranosyl)cytosine (ECyd, 3)6b-d were po-
tent antitumor nucleosides which significantly inhibited
the growth of various human solid tumor cells both in
vitro and in vivo.
However, only a few examples of 4′-branched nucleo-
sides have been reported,7-10 and their biological activi-
ties have not yet been investigated in a systematic
manner. This may be because efficient synthetic meth-
ods for 4′-branched nucleosides had not been developed.7
Recently, Ohrui and co-workers synthesized several 4′R-
S0022-3263(97)01703-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/22/1998

Radical Synthesis of 4′R-Branched 2′-Deoxyadenosines
J . Org. Chem., Vol. 63, No. 3, 1998 747
branched nucleoside derivatives and found that 4′R-C-
methyl-2′-deoxycytidine (4) has very strong growth in-
hibitory activity against leukemic cells.8 They synthesized
4 by deoxygenating the 2′-position of the corresponding
4′-branched ribonucleoside analogue, which was prepared
via a glycosylation reaction of the corresponding 4R-C-
methyl sugar synthesized from D-glucose.8 As a result
of the very long reaction steps, the overall yield was low.
Consequently, the antileukemic activity of 4 was inves-
tigated in vitro only. To examine the biological effects
of various 4′-branched nucleosides, the development of
more straightforward synthetic methods is needed. In
this paper, we describe an efficient synthetic method for
4′R-branched-2′-deoxyadenosines, using an intramolecu-
lar radical cyclization reaction with a novel silicon-
containing tether11 as a key step.
Radical cyclization is a highly versatile method for
forming C-C bonds.12 There has been growing interest
in the use of silicon-containing tethers for intramolecular
radical cyclization reactions.13 These are very useful for
regio- and stereoselective introduction of a carbon sub-
stituent based on a temporary silicon connection. Re-
cently, we developed a regio- and stereoselective method
for introducing 1-hydroxyethyl or 2-hydroxyethyl groups
at the â-position of a hydroxyl group in halohydrins or
R-(phenylseleno)alkanols using an intramolecular radical
cyclization reaction with dimethyl- or diphenylvinylsilyl
group as a radical acceptor tether (Scheme 1).11 The
selective introduction of both a 1-hydroxyethyl and a
2-hydroxyethyl groups can be achieved via a 5-exo-
cyclization intermediate (E) or a 6-endo-cyclization in-
termediate (F ), respectively, after oxidative ring-cleavage
by treating the cyclization products under Tamao oxida-
tion conditions,14 as shown in Scheme 1. With a 2-bro-
moindanol derivative as a substrate, we also demon-
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748 J . Org. Chem., Vol. 63, No. 3, 1998
Shuto et al.
Sch em e 1
We used N6,N6,3′-O-tribenzoyl-2′-deoxyadenosine (5) as
a protected nucleoside for further derivatization because
of its easy preparation from 2′-deoxyadenosine. Thus, 5
was treated under Swern oxidation conditions followed
by treatment with PhSeCl and Et3N in CH2Cl2,16 which
afforded the 4′-(phenylseleno) derivative 6 in 72% yield
as a diastereomeric mixture at the 4′-position. When the
formyl group was reduced with Bu4NBH3CN in THF,16
the resulting diastereomeric mixture was successfully
separated by silica gel column chromatography to give
the 4′â-(phenylseleno) derivative 7 and 4′R-(phenylseleno)
derivative 8 in yields of 72% and 21%, respectively
(Scheme 4). The 4′â-(phenylseleno) derivative 7 was
treated with diphenylvinylchlorosilane and Et3N in the
presence of DMAP in toluene17 to give vinylsilyl deriva-
tive 9, a substrate for the radical reaction, in 84% yield.
A solution of 1.5 equiv of Bu3SnH and AIBN in benzene
was added slowly over 8 h, using a syringe-pump, to a
solution of 9 in benzene at 80 °C. The resulting crude
product was subsequently treated under Tamao oxidation
conditions, to give cyclonucleoside 11 in 35% yield as the
major product. The structure of 11, including stereo-
chemistry, was confirmed by HMBC and NOESY spectra
after converting it into the corresponding triacetate 12.
Although the radical reaction of 9 was investigated under
various conditions, the desired 4′-branched nucleosides
were not obtained. This result suggests a tandem radical
cyclization mechanism, shown in Scheme 5: a 5-exo-
cyclized radical intermediate was first produced from the
4′-radical which did not react with Bu3SnH to give the
desired 13 or 14 but rapidly added to the 8-position of
the adenine moiety. The 8-hydrogen was subsequently
abstracted by a phenylseleno radical to afford 10. Similar
formations of cyclo-adenine nucleosides via intramolecu-
lar radical additions at the adenine 8-position have been
previously reported by our laboratory (Scheme 6).18
We subsequently introduced the silicon tether at the
3′-hydroxyl group of the 4′-(phenylseleno) adeninenucleo-
side derivative and investigated its radical reactions
(Scheme 7). The primary hydroxyl group of 4′â-(phen-
ylseleno) nucleoside 15, prepared from 7, was selectively
protected by a dimethoxytrityl (DMTr) group to give 16
quantitatively. Treatment of 16 with diphenylvinylchlo-
rosilane under similar conditions to those described above
gave 17, a substrate for the radical reaction, in 93% yield.
Sch em e 2
strated that the radical cyclization was irreversible, and
that kinetically favored 5-exo-cyclized radical C, formed
from radical B, was trapped when the concentration of
Bu3SnH was high enough to give E. At lower concentra-
tions of Bu3SnH and higher reaction temperatures,
radical C rearranged into the more stable ring-enlarged
4-oxa-3-silacyclohexyl radical D which was then trapped
with Bu3SnH to give F .11
Tanaka and co-workers reported that intermolecular
carbon radical addition reactions on 4′,5′-dehydro nucleo-
side derivatives did not give 4′-addition products but gave
5′-addition products exclusively as a diastereomeric
mixture at the 4′-position (Scheme 2a).7c This result
suggested generation of a radical at the 4′-position of
nucleosides which subsequently added to an olefinic bond
thereby introducing carbon substituents at the 4′-position
(Scheme 2b). Therefore, we planned to explore a new
method for producing 4′R-branched nucleosides via in-
tramolecular radical cyclization reactions of the diphen-
ylvinylsilyl group as a radical acceptor tether. Our
synthetic strategy is outlined in Scheme 3.15 If the
radical cyclization reaction with 4′-(phenylseleno)-2′-
deoxynucleoside derivatives II or III proceeds as we
expect, these would give the corresponding ring-closure
products, IV and/or V, or VI and/or VII, respectively.
Subsequent oxidative ring-cleavage reactions of the
products would give the desired 4′R-branched nucleoside
analogues VIII and/or IX.
Resu lts a n d Discu ssion
We used 2′-deoxyadenosine as a starting material,
since a method for introducing a phenylseleno group at
the 4′-position of 3′-O-acetyl-N6,N6-dibenzoyl-2′-deoxy-
adenosine has been developed by Giese and co-workers.16
(17) Sieburth, S. M.; Fensterbank, L. J . Org. Chem. 1992, 57, 5279-
5281.
(18) (a) Matsuda, A.; Muneyama, T.; Nishida, T.; Sato, T.; Ueda, T.
Nucleic Acids Res. 1976, 3, 3349-3357. (b) Matsuda, A.; Tezuka, M.;
Niizuma, K.; Sugiyama, E.; Ueda, T. Tetrahedron 1978, 34, 2633-
2637. (c) Usui, H.; Ueda, T. Chem. Pharm. Bull. 1986, 34, 15-23. (d)
Usui, H.; Ueda, T. Chem. Pharm. Bull. 1986, 34, 1518-1523. (e) Usui,
H.; Matsuda, A.; Ueda, T. Chem. Pharm. Bull. 1986, 34, 1961-1967.
(15) A part of this study has been described in a communication
(ref 11).
(16) Giese, B.; Erdmann, P.; Schafer, T.; Schwitter, U. Synthesis
1994, 1310-3112.

Radical Synthesis of 4′R-Branched 2′-Deoxyadenosines
Sch em e 3
J . Org. Chem., Vol. 63, No. 3, 1998 749
Sch em e 4
Sch em e 5
Sch em e 6
Treatment of 17 with 3.0 equiv of Bu3SnH at 80 °C in
benzene in the presence of AIBN, followed by Tamao
oxidation gave a diastereomeric mixture of 4′R-(1-hy-
droxyethyl) derivatives 19 (the ratio of major and minor
diastereomers was 2:1 from the 1H NMR spectrum) which
were derived from a 5-exo-cyclized product 18, in almost
quantitative yield. When a solution of 1.1 equiv of
Bu3SnH and AIBN (0.17 equiv) in toluene was added
slowly over 4 h to a solution of 17 in toluene at 110 °C,
the regioselectivity was completely reversed. The reac-
tion did not give 18 at all, but rather 6-endo-cyclized 20
in 91% yield. Tamao oxidation of 20 gave 4′R-(2-hy-
droxyethyl) derivative 21 in 79% yield (Scheme 7).

750 J . Org. Chem., Vol. 63, No. 3, 1998
Shuto et al.
Sch em e 7
Sch em e 8
F igu r e 2.
The diastereomeric mixture 19 was converted to the
corresponding isopropylidene derivatives which were
successfully separated into the major diastereomer 23a
and the minor 23b by silica gel column chromatography
(Scheme 8). From the NOESY spectra, the stereochem-
istries at the 4′-branched moiety of 23a and 23a were
determined as S and R, respectively.19
the 5′-methylene group, of the methylene protons â to
the silicon was exclusively replaced by a deuterium in
25 (Figure 2). This may be explained by substrate
control.12b With regard to the radical intermediate,
conformer J would be favored over I, due to steric
repulsion between the axial phenyl group and tetahy-
drofuran ring in I. The bulky axial phenyl group of J
may lead to equatorial attack of Bu3SnD(H) (Scheme 9).
From these results, a radical reaction mechanism with
an adenine nucleoside as a substrate, as shown in
Scheme 10, was suggested, and the mechanism is con-
sistent with that with 2-bromoindanol derivatives.11
Therefore, it was suggested that this rearrangement
reaction may be general in (3-oxa-2-silacyclopentyl)methy
radicals. To the best of our knowledge, such a ring-
enlarging 1,2-radical rearrangement reaction of â-silyl
radicals has not been previously reported.22-25 Thereac-
tion mechanism of this rearrangement is not fully
understood. However, it is known that â-silyl carbon-
From the results of the radical reaction, it appeared
that formation of the 6-endo product 20 was not kinetic
but possibly thermodynamic, since the ratio of the endo-
and exo-products should be independent of the concentra-
tion of Bu3SnH, if the reaction is kinetically controlled.
To clarify the reaction mechanism, we performed the
reaction with Bu3SnD. The reaction of 17 in the presence
of excess of Bu3SnD gave 5-exo cyclized 2420,21 (Figure 2)
with high selectivity which was deuterated exclusively
at the methyl position. With a much lower Bu3SnD
concentration, the reaction gave 2521 (Figure 2) as the
sole product, in which one methylene proton at the
â-position of the silicon was exclusively replaced by
1
deuterium based on its H NMR spectrum. It is interest-
ing that the proton which has a trans-configuration to
(20) Isolation of the radical reaction products was attempted, but
was difficult due to contamination with compounds derived from
Bu3SnH.
(21) The structures of 24 and 25 were further confirmed from the
instrumental analyses of their Tamao oxidation products 26 and 27.
(19) An evident cross peak between the H-1′ and the methine proton
of the 4′R-branched chain siganals was observed in the NOESY
spectrum of 23a .

Radical Synthesis of 4′R-Branched 2′-Deoxyadenosines
J . Org. Chem., Vol. 63, No. 3, 1998 751
Sch em e 9
Sch em e 11
Sch em e 10
Sch em e 12
centered radicals are easily generated and are stable
compared with their all-carbon analogues.26 Also, the
Si-C bond (69-76 kcal mol-1) is weaker than the C-C
bond (83 kcal mol-1),27 and these effects may affect this
rearrangement. Two intermediates, a fragmentation
intermediate K and a silicon-bridging one L, may be
postulated (Scheme 11). Recently, Giese and co-workers
described a novel radical substitution reaction and
proposed a silicon-bridging intermediate M (Scheme
12a)28 that is analogous to the intermediate L. Pentava-
lent-like silicon radicals have also been suggested as
intermediates of free radical 1,2-silicon shifts from carbon
to nitrogen or oxygen by Harris and co-workers (Scheme
12b).25a On the other hand, Tsai and Cherng reported a
radical Brook rearrangement as shown in Scheme 12c.25b
Although, Tsai and Cherng did not discuss the mecha-
nism in their paper, the rearrangement may also proceed
via pentavalent-like silicon radical intermediates, since
the rearrangement cannot proceed via a fragmentation
mechanism. This kind of interaction between silicon and
the unpaired electron in a â-silyl radical has been
suggested29 through kinetic study,26a,29a MO calculation,29b
and ESR study.29c,d Accordingly, the rearrangement of
â-silyl radicals found in this study, as well as the previous
results of Giese et al., Harris et al., and Tsai et al., may
suggest the participation of pentavalent-like silicon
intermediates in radical reactions of some organosilicon
compounds.
Derivatization of 19 and 21 into various 4′R-branched-
chain sugar nucleosides and their biological evaluations
are under investigation.
Exp er im en ta l Section
(22) There is no precedent for the ring-enlarging 1,2-rearrangement
of a carbon-centered â-silyl radical analogous to this reaction, except
for our recent communication (ref 11).
(23) Known 1,2-rearrangement of carbon-centered radicals: (a) Wilt,
J . W.; Pawlikowski, W. W., J r. J . Org. Chem. 1975, 40, 3641-3644.
(b) Goermer, R. N.; Cote P. N., J r.; Bittimberga, B. M. J . Org. Chem.
1977, 42, 19-28. (c) Stork, G.; Mook, R., J r. J . Am. Chem. Soc. 1987,
109, 2829-2881. (d) Beckwith, A. L. J .; O’Shea, D. M.; Westwood, S.
W. J . Am. Chem. Soc. 1988, 110, 2565-2575. (e) Dowd, P.; Ahang, W.
Chem. Rev. 1993, 93, 2091-2115.
(24) A gas phase 1,2-migration of trimethylsilyl group in an aromatic
â-silyl biradical has been reported: J ohnson, G. C.; Stofko, J . J ., J r.;
Lockhart, T. P.; Brown, D. W.; Bergman, R. G. J . Org. Chem. 1979,
44, 4215-4218.
(25) Carbon to oxygen or carbon to nitrogen 1,2-silicon migrations
in oxygen- or nitrogen-centered â-silyl radicals have been known: (a)
Harris, J . M.; Macinnes, I.; Walton, J . C.; Maillard, B. J . Organomet.
Chem. 1991, 403, C25-C28. (b) Tsai, Y.-M.; Cherng, C.-D. Tetrahedron
Lett. 1991, 32, 3515-3518.
(26) (a) Auner, N.; Walsh, R.; Westrup, J . J . Chem. Soc., Chem.
Commun. 1986, 207-208. (b) Davidson, I. M. T.; Barton, T. J .; Hughes,
S.; Ijadi-Maghsoodi, S.; Revis, J .; Paul, G. C. Organometallics 1987,
6, 644-647.
(27) Hess, G. G.; Lampe, F. W.; Sommer, L. H. J . Am. Chem. Soc.
1965, 87, 5327-2533.
(28) Kulicle, K. J .; Chatgiliatoglu, C.; Kopping, B.; Giese, B. Helv.
Chim. Acta 1992, 75, 935-939.
Melting points are uncorrected. NMR spectra were recorded
at 270 or 500 MHz (1H) and at 125 MHz (13C) and are reported
in ppm downfield from TMS. J values are given in hertz. Mass
spectra were obtained by electron ionization (EI) or fast atom
bombardment (FAB) method. Thin-layer chromatography was
done on Merck coated plate 60F254. Silica gel chromatography
was done with Merck silica gel 5715. Reactions were carried
our under an argon atmosphere.
N6,N6,O-Tr iben zoyla d en osin e (5). A mixture of 2′-deoxy-
adenosine (5.0 g, 20 mmol) and DMTrCl (15.7 g, 46 mmol) in
pyridine (50 mL) was stirred at room temperature for 5 h. To
the solution was added BzCl (11.6 mL, 100 mmol), and the
resulting mixture was stirred at room-temperature overnight.
The resulting solution was evaporated under reduced pressure,
and the residue was partitioned between EtOAc and H2O. The
organic layer was washed with brine, dried (Na2SO4), and
evaporated under reduced pressure. After the residue was
(29) {a) J ackson, R. A.; Ingold, K. U.; Griller, D.; Nazran, A. S. J .
Am. Chem. Soc. 1985, 107, 208-211. (c) Pitt, C. G. J . Organomet.
Chem. 1973, 61, 49-70. (c) Shen, K. S.; Kochi, J . K. J . Am. Chem.
Soc. 1974, 96, 1383-1391. (d) Griller, D.; Ingold, K. U. J . Am. Chem.
Soc. 1974, 96, 6715-6720.

752 J . Org. Chem., Vol. 63, No. 3, 1998
Shuto et al.
dissolved in CH2Cl2 (300 mL), TFA (7.6 mL, 100 mmol) was
added, and the mixture was stirred at room temperature for
1 h. The mixture was cooled in an ice-bath, aqueous NaHCO3
(saturated, 100 mL) was added, and then the mixture was
partitioned. The organic layer was washed with aqueous
NaHCO3 (saturated), H2O, and brine, dried (Na2SO4), and
evaporated under reduced pressure. The residue was purified
by column chromatography (SiO2, 50% EtOAc in hexane) to
give 5 (7.4 g, 66%) as a foam: 1H NMR (270 MHz, CDCl3) δ
8.66 (s, 1 H), 8.20 (s, 1 H), 8.10-7.35 (m, 15 H), 6.46 (dd, 1 H,
J ) 9.8, 5.4), 5.81 (m, 1 H, J ) 5.6), 4.46 (m, 1 H), 4.01 (s, 2
H), 3.28 (ddd, 1H, J ) 9.8, 14.3, 5.6), 2.64 (dd, 1 H, J ) 5.4,
14.3); 13C NMR (100 MHz, CDCl3) δ 172.02, 165.73, 151.76,
151.51, 144.21, 133.75, 133.46, 133.05, 129.84, 129.57, 129.36,
129.27, 128.70, 128.63, 128.46, 87.49, 87.30, 77.21, 63.14,
38.08, 36.50; EI-MS m/z 563 (M+). Anal. Calcd for C31H25N5-
O6‚3/2H2O: C, 63.05; H, 4.78; N, 11.86. Found: C, 63.20; H,
4.49; N, 11.67.
A Dia ster eom er ic Mixtu r e of 9-(3-O-Ben zoyl-2-d eoxy-
4-(p h en ylselen o)-r-L-th r eo-p en t o-5-a ld o-1,4-fu r a n osyl)-
N6,N6-d iben zoyla d en in e a n d 9-(3-O-Ben zoyl-2-d eoxy-4-
(p h en ylselen o)-â-D-er yth r o-p en t o-5-a ld o-1,4-fu r a n osyl)-
N6,N6-d iben zoyla d en in e (6). A mixture of oxalyl chloride
(0.86 mL, 8.8 mmol) and DMSO (1.54 mL, 22 mmol) in CH2Cl2
(8 mL) was stirred at -78 °C for 10 min, and a solution of 5
(2.5 g, 4.4 mmol) in CH2Cl2 (15 mL) was added, and the
resulting mixture was further stirred at the same temperature
for 30 min. Et3N (2.42 mL, 17.6 mmol) was added, and the
resulting mixture was stirred at the same temperature for 1.5
h. The resulting solution was used directly for the next
selenation reaction.
nylvinylchlorosilane (500 µL, 2.1 mmol), DMAP (30 mg, 0.28
mmol), and Et3N (300 µL, 2.1 mmol) in toluene (25 mL) was
stirred at room temperature for 30 min. After insoluble
materials were filtered off, the filtrate was evaporated under
reduced pressure, and the residue was partitioned between
EtOAc and H2O. The organic layer was washed with brine,
dried (Na2SO4), and evaporated under reduced pressure. The
residue was purified by column chromatography (SiO2, 50%
EtOAc in hexane) to give 9 (1.1 g, 84%) as a form: 1H NMR
(270 MHz, CDCl3) δ 8.63 (s, 1 H, H-8), 8.48 (s, 1 H), 7.99-
7.07 (m, 30 H), 6.63 (dd, 1 H, J ) 6.9, 6.9), 6.32 (dd, 1 H, J )
15.0, 19.9), 6.17 (dd, 1 H, J ) 15.0, 4.2), 6.08 (dd, 1 H, J ) 6.2,
3.9), 5.80 (dd, 1 H, J ) 19.9, 4.2), 4.21 (d, 2 H, J ) 11.5), 3.24
(ddd, 1 H, J ) 13.7, 6.9, 6.2), 2.89 (ddd, 1 H, J ) 13.7, 6.9,
3.9); FAB-MS m/z 928 (MH+). Anal. Calcd for C51H41
-
N5O6SeSi‚H2O: C, 64.82; H, 4.59; N, 7.41. Found: C, 64.54;
H, 4.26; N, 7.54.
(5′S)-4′-C-(Hyd r oxym eth yl)-2′-d eoxy-8,5′-m eth a n oa d e-
n osin e (11). To a solution of 9 (185 mg, 0.20 mmol) in benzene
(20 mL) at 80 °C was added a solution of Bu3SnH (160 µL, 3.0
mmol) and AIBN (50 mg, 0.30 mmol) in benzene (20 mL) slowly
over 8 h. The solvent was evaporated under reduced pressure,
and the residue was partitioned between MeCN and hexane.
The MeCN layer was evaporated under reduced pressure, the
residue was dissolved in MeOH/THF (1:1, 6 mL), aqueous H2O2
(30%, 112 µL, 1.0 mmol), KF (60 mg, 1.0 mmol), and KHCO3
(32 mg, 0.32 mmol) were added, and the resulting mixture was
stirred at room temperature for 15 h. Aqueous Na2S2O3 (1
M, 20 mL) was added, and the resulting insoluble materials
were filtered off. The filtrate was evaporated under reduced
pressure, and the residue was purified by column chromatog-
raphy (SiO2, 20% MeOH in CHCl3) to give 11 (20 mg, 35%) as
a syrup: HRMS (EI) calcd for C12H15N5O4 293.1124, found
293.1116. This compound was acetylated as follows without
further purification.
(5′S)-3′5′-Di-O-a cet yl-4′-C-(a cet oxym et h yl)-2′-d eoxy-
8,5′-m eth a n oa d en osin e (12). A solution of 11 (23 mg, 0.08
mmol), acetic anhydride (44 µL, 0.47 mmol), Et3N (µL, 0.47
mmol), and DMAP (10 mg, 0.08 mmol) in MeCN (2 mL) was
stirred at room temperature for 5 min. After EtOH was added,
the solvent was evaporated under reduced pressure. The
residue was purified by column chromatography (SiO2, 50%
EtOAc in hexane) to give 12 (19 mg, 58%) as a solid: 1H NMR
(270 MHz, CDCl3) δ 8.27 (s, 1 H, H-2), 6.78 (dd, 1 H, H-1′, J )
2.9, 7.6), 6.32 (s, 2 H, NH2), 5.82 (dd, 1 H, H-3′, J ) 6.7, 3.0),
5.36 (dd, 1 H, H-5′, J ) 4.2, 11.6), 4.59 (d, 1 H, 4′R-CH2OAc,
J ) 12.3), 4.20 (d, 1 H, 4′R-CH2OAc, J ) 12.3), 3.61 (dd, 1 H,
5′-CH2-, J ) 4.2, 15.6), 3.07 (dd, 1 H, 5′-CH2-, J ) 11.6, 15.6),
2.81 (m, 2 H, H-2′), 2.18, 2.12, 2.03 (each s, each 3 H), the
assignments were in agreement with COSY spectrum; 13C
NMR (125 MHz, CDCl3) δ 170.64, 170.03, 169.09, 154.94,
152.44, 145.71, 89.47, 81.84, 74.43, 67.21, 63.38, 42.60, 31.08,
21.29, 21.05, 20.82; HRMS (EI) calcd for C18H21N5O7 419.1439,
found 419.1430.
9-(2-Deoxy-4-(p h en ylselen o)-r-L-th r eo-p en to-1,4-fu r a -
n osyl)-N6-ben zoyla d en in e (15). A mixture of 7 (2.6 g, 3.6
mmol) and K2CO3 (500 mg, 3.6 mmol) in MeOH (40 mL) was
stirred at room temperature for 10 min, to which was added a
solution of saturated NH3 in MeOH (40 mL), and the resulting
mixture was stirred for 10 min. The solvent was evaporated
under reduced pressure, and the residue was purified by
column chromatography (SiO2, 16% MeOH in CHCl3) to give
15 (1.3 g, 69%) as a white powder: 1H NMR (500 MHz, CDCl3)
δ 9.03 (s, 1 H), 8.84 (s, 1 H), 8.59 (s, 1 H), 8.06-7.19 (m, 10
H), 6.94 (dd, 1 H, J ) 8.2, 6.7), 4.87 (m, 1 H), 3.93 (m, 2 H),
3.74 (d, 1 H, J ) 3.7), 3.20 (ddd, 1 H, J ) 13.7, 8.2, 5.1), 2.83
(ddd, 1 H, J ) 13.7, 6.7, 1.5), 2.69 (m, 1 H); 13C NMR (100
MHz, DMSO-d6) δ 165.40, 152.11, 151.54, 150.08, 142.70,
136.38, 133.18, 132.24, 128.56, 128.30, 126.75, 126.68, 125.45,
99.07, 83.75, 75.41, 62.56, 60.28. Anal. Calcd for C23H21N5-
O4Se: C, 54.12; H, 4.15; N, 13.72. Found: C, 53.99; H, 4.10;
N, 13.57.
After a solution of PhSeCl (2.53 g, 13.2 mmol) in CH2Cl2
(40 mL) was cooled to -78 °C, Et3N (3.63 mL, 26.4 mmol) was
added, and the resulting solution was added slowly to the
above prepared solution. The resulting mixture was stirred
at -78 °C for 30 min and then at 0 °C for 1.5 h. The solvent
was evaporated under reduced pressure, and the residue was
purified by column chromatography (SiO2, 50% EtOAc in
hexane) to give 6 (2.25 g, 72%) as a foam: 1H NMR (270 MHz,
CDCl3) δ 9.37 (s, 1 H), 8.70 (s, 1 H), 8.60 (s, 1 H), 7.98-7.22
(m, 20 H), 6.95 (dd, 1 H, J ) 8.4, 6.4), 6.17 (dd, 1 H, J ) 5.1,
1.4), 3.59 (ddd, 1 H, J ) 8.4, 14.0, 5.1), 3.03 (ddd, 1 H, J ) 6.4,
14.0, 1.4); FAB-MS m/z 718 (MH+). Anal. Calcd for C37H27
-
N5O6Se‚H2O: C, 60.49; H, 3.98; N, 9.53. Found: C, 60.35; H,
3.61; N, 9.41.
9-(3-O-Ben zoyl-2-deoxy-4-(ph en ylselen o)-r-L-th r eo-pen -
to-1,4-fu r a n osyl)-N6,N6-d iben zoyla d en in e (7) a n d 9-(3-O-
Ben zoyl-2-d eoxy-4-(p h en ylselen o)-â-D-er yth r o-p en to-1,4-
fu r a n osyl)-N6,N6-d iben zoyla d en in e (8). To a solution of
6 (2.25 g, 3.1 mmol) in THF (30 mL) was added a solution of
Bu4NBH3CN (1.58 g, 5.6 mmol) in THF (30 mL) at -78 °C,
and the mixture was stirred at the same temperature for 15
min and then at 0 °C for 1.5 h. After aqueous tartaric acid
(5%) was added, the solvent was evaporated under reduced
pressure, and the residue was purified by column chromatog-
raphy (SiO2, 50% EtOAc in hexane) to give 7 (1.58 g, 72%)
and 8 (0.46 g, 21%) as forms. 7: 1H NMR (270 MHz, CDCl3)
δ 8.61 (s, 2 H), 8.06-7.29 (m, 20 H), 6.89 (dd, 1 H, J ) 7.9,
6.7), 6.01 (dd, 1 H, J ) 5.4, 2.1), 3.82 (m, 2 H), 3.45 (ddd, 1 H,
J ) 14.0, 7.9, 5.4), 2.96 (ddd, 1 H, J ) 14.0, 6.7, 2.1), 2.30 (t,
1 H, J ) 6.9); 13C NMR (100 MHz, CDCl3) δ 172.04, 165.16,
152.82, 152.31, 151.88, 143.20, 136.67, 133.89, 133.67, 132.88,
129.68, 129.40, 129.31, 128.71, 128.59, 128.51, 127.35, 125.33,
97.37, 84.52, 77.82, 77.19, 63.06, 38.18; FAB-MS m/z 720
(MH+). Anal. Calcd for C37H29N5O6Se‚H2O: C, 60.33; H, 4.24;
N, 9.51. Found: C, 60.04; H, 3.87; N, 9.31. 8: 1H NMR (270
MHz, CDCl3) δ 8.64 (s, 1 H), 8.25 (s, 1 H), 8.19-7.30 (m, 20
H), 6.60 (dd, 1 H,J ) 6.7, 6.7), 6.24 (dd, 1 H, J ) 7.2, 4.1),
4.02 (d, 1 H, J ) 12.4), 4.79 (d, 1 H, J ) 12.4), 3.33 (ddd, 1 H,
J ) 7.2, 6.7, 10.8), 2.83 (ddd, 1 H, J ) 6.7, 4.1, 10.8); FAB-MS
m/z 720 (MH+). Anal. Calcd for C37H29N5O6Se‚H2O: C, 60.33;
H, 4.24; N, 9.51. Found C, 60.21; H, 4.00; N, 9.34.
9-(3-O-Ben zoyl-2-d eoxy-5-O-d ip h en ylvin ysilyl-4-(p h e-
n ylselen o)-r-L-th r eo-p en t o-1,4-fu r a n osyl)-N6,N6-d ib en -
zoyla d en in e (9). A mixture of 7 (1.0 g, 1.4 mmol), diphe-
9-(2-Deoxy-5-O-(d im et h oxyt r it yl)-4-(p h en ylselen o)-r-
L-th r eo-p en t o-1,4-fu r a n osyl)-N6-b en zoyla d en in e (16). A
mixture of 15 (1.5 g, 3.0 mmol) and DMTrCl (1.2 g, 3.7 mmol)

Radical Synthesis of 4′R-Branched 2′-Deoxyadenosines
J . Org. Chem., Vol. 63, No. 3, 1998 753
in pyridine (30 mL) was stirred at room temperature for 48 h.
After EtOH (1 mL) was added, and the solution was stirred
for 10 min. The resulting solution was evaporated under
reduced pressure, and the residue was partitioned between
EtOAc and H2O. The organic layer was washed with brine,
dried (Na2SO4), and evaporated under reduced pressure. The
residue was purified by column chromatography (SiO2, 2%
MeOH-CHCl3) to give 16 (2.5 g, quant): 1H NMR (500 MHz,
CDCl3+D2O) δ 8.81(s, 1 H), 8.48 (s, 1 H), 8.04-6.79 (m, 23
H), 6.87 (dd, 1 H, J ) 7.4, 5.9), 4.82 (m, 1 H), 3.80 (s, 6 H),
3.66 (d, 1 H, J ) 10.3), 3.55 (d, 1 H, J ) 10.3), 3.04 (ddd, 1 H,
J ) 13.3, 7.4, 5.9), 2.75 (dd, 1 H, J ) 13.3, 6.4); 13C NMR (67.8
MHz, CDCl3) δ 164.65, 158.67, 152.85, 151.93, 149.49, 143.90,
141.73, 135.56, 134.91, 134.81, 133.59, 132.72, 129.81, 129.06,
128.79, 128.52, 128.27, 128.05, 127.82, 127.06, 122.91, 113.38,
96.43, 87.22, 84.96, 77.95, 77.22, 64.96, 55.17, 40.22; FAB-MS
m/z 814 (MH+). Anal. Calcd for C44H39N5O6Se‚1/2H2O: C,
64.31; H, 4.91; N, 8.52. Found: C, 64.30; H, 4.93; N, 8.35.
6-En d o-Cycliza tion P r od u ct 20. To a solution of 17 (2.2
g, 2.2 mmol) in toluene (180 mL) at 110 °C, was added a
solution of Bu3SnH (820 µL, 3.00 mmol) and AIBN (50 mg,
0.30 mmol) in toluene (25 mL) slowly over 4 h. The solvent
was evaporated under reduced pressure, and the residue was
partitioned between MeCN and hexane. The MeCN layer was
evaporated under reduced pressure, and the residue was
purified by column chromatography (SiO2, 50% EtOAc in
hexane) to give 20 (1.7 g, 91%) as a white foam; 1H NMR (500
MHz, CDCl3) δ 8.97 (s, 1 H, NH), 8.68 (s, 1 H, H-8), 8.00 (s, 1
H, H-2), 8.03-6.74 (m, 28 H, Ph), 6.52 (dd, 1 H, H-1′, J ) 6.0,
8.4), 4.96 (m, 1 H, H-3′), 3.77 (s, 6 H, MeO x 2), 3.36 (d, 1 H,
H-5′a, J ) 9.7), 3.21 (d, 1 H, H-5′b, J ) 9.7), 2.95 (ddd, 1 H,
H-2′a, J ) 13.7, 8.4), 2.68 (dd, 1 H, H-2′b, J ) 13.7, 6.0), 2.44
(ddd, 1 H, H-6′a, J ) 14.0, 10.4, 3.6), 2.16 (ddd, 1 H, H-6′b, J
) 14.0, 8.7, 4.1), 1.41 (ddd, 1 H, H-7′a, J ) 15.0, 10.4, 4.1),
1.12 (ddd, 1 H, H-7′b, J ) 15.0, 8.7, 3.6), the carbons introduced
at the 4′R-position were numbered C-6′ and C-7′, and the
assignments were in agreement with COSY spectrum; NOE,
irradiated H-3′, observed H-1′ (1.0%), H-5′a (1.6%), H-5′b
(1.2%), H-2′a (3.5%), and H-2′b (1.2%); irradiated H-6′a,
observed H-3′ (1.6%), H-5′a (0.4%), H-5′b (0.3%), H-6′b (16%),
H-7′a (0.3%), and H-7′b (0.08%); irradiated H-6′b, observed
H-1′ (1.7%), H-5′b (1.5%), H-6′a (16%), H-7′a (0.9%), and H-7′b
(1.6%); 13C NMR (100 MHz, CDCl3) δ 164.41, 158.36, 158.34,
152.34, 151.32, 149.27, 144.22, 141.46, 135.37, 134.47, 134.31,
134.23, 134.15, 133.61, 132.61, 130.36, 130.18, 129.89, 129.83,
128.74, 128.10, 128.00, 127.97, 127.77, 127.71, 126.80, 123.39,
113.07, 87.94, 86.42, 84.99, 76.47, 67.40, 55.20, 40.91, 27.32,
9-(2-Deoxy-5-O-(d im eth oxytr ityl)-3-O-(d ip h en ylvin yl-
silyl)-4-(p h en ylselen o)-r-L-th r eo-p en to-1,4-fu r a n osyl)-N6-
ben zoyla d en in e (17). A mixture of 16 (1.8 g, 2.2 mmol),
DMAP (54 mg, 0.44 mmol), Et3N (590 µL, 4.4 mmol), and
diphenylvinylchlorosilane (980 µL, 4.4 mmol) in toluene (30
mL) was stirred at room temperature for 15 h. Insoluble
materials were filtered off, and the filtrate was evaporated
under reduced pressure. The residue was partitioned between
EtOAc and H2O. The organic layer was washed with brine,
dried (Na2SO4), and evaporated under reduced pressure. The
residue was purified by column chromatography (SiO2, 60%
EtOAc in hexane) to give 17 (1.7 g, 93%) as a foam: 1H NMR
(500 MHz, CDCl3) δ 8.98 (s, 1 H), 8.72 (s, 1 H), 8.19 (s, 1 H),
8.05-6.75 (m, 33 H), 6.65 (dd, 1 H, J ) 6.5, 5.9), 6.23 (dd, 1
H, J ) 20.0, 14.9), 6.13 (dd, 1 H, J ) 14.9, 4.0), 5.71 (dd, 1 H,
J ) 20.0, 4.0), 4.88 (dd, 1 H, J ) 5.9, 5.6), 3.87 (d, 1 H, J )
10.0), 3.77 (s, 6 H), 3.27 (d, 1 H, J ) 10.0), 2.89 (ddd, 1 H, J )
13.0, 5.9, 5.9), 2.77 (ddd, 1 H, J ) 13.0, 6.5, 5.6); 13C NMR
(100 MHz, CDCl3) δ 164.44, 158.22, 152.48, 151.39, 149.25,
141.63, 138.11, 136.82, 135.79, 135.64, 135.01, 134.89, 133.57,
133.05, 132.38, 130.24, 130.18, 128.76, 128.58, 128.54, 128.26,
127.89, 127.86, 127.75, 127.67, 126.79, 126.59, 123.03, 112.97,
112.94, 96.28, 86.84, 84.36, 77.21, 65.81, 55.16, 39.37; FAB-
MS m/z 1022 (MH+). Anal. Calcd for C58H51N5O6SeSi‚H2O:
C, 67.04; H, 5.14; N, 6.74. Found: C, 66.83; H, 4.95; N, 6.64.
4.84; HRMS (FAB) calcd
C52H48O6N5Si 866.3374, found
866.3394. Similar reaction of 17 (102 mg, 0.10 mmol) with
Bu3SnD, instead of Bu3SnH, gave deuterium-labeled 25 (63
mg, 73%): HRMS (FAB) calcd C52H47DO6N5Si 867.3433, found
867.3467.
2′-Deoxy-5′-O-(d im et h oxyt r it yl)-4-C-(2-h yd r oxyet h y-
l)a d en osin e (21). A mixture of 20 (430 mg, 0.50 mmol),
aqueous H2O2 (30%, 280 µL, 2.5 mmol), KF (150 mg, 2.5 mmol),
and KHCO3 (80 mg, 0.80 mmol) in MeOH/THF (1:1, 10 mL)
was stirred at room temperature for 15 h. Aqueous Na2S2O3
(1 M, 20 mL) was added, and the resulting insoluble materials
were filtered off. The filtrate was evaporated under reduced
pressure, and the residue was purified by column chromatog-
raphy (SiO2, 8% MeOH in CHCl3) to give 21 (240 mg, 79%) as
a syrup: 1H NMR (500 MHz, CDCl3) δ 8.23 (s, 1 H), 7.87 (s, 1
H), 7.36-6.48 (m, 13 H), 6.48 (dd, 1 H, J ) 6.6, 6.1), 5.61 (s,
2 H), 4.51 (dd, 1 H, J ) 6.0, 3.0), 3.87 (m, 1 H), 3.78 (s, 6 H),
3.71 (m, 1 H), 3.39 (d, 1 H, J ) 9.9), 3.24 (d, 1 H, J ) 9.9),
2.93 (ddd, 1 H, J ) 13.6, 6.6, 6.0), 2.55 (ddd, 1 H, J ) 13.6,
6.1, 3.0), 2.18 (m, 2 H); FAB-MS m/z 596 (MH+). Anal. Calcd
for C33H35N5O6‚MeOH: C, 65.04; H, 5.94; N, 11.16. Found:
C, 64.98; H, 6.07; 11.05. Similar reaction of 25 (44 mg, 0.050
mmol) gave 27 (28 mg, 94%): HRMS (FAB) calcd for
2′-Deoxy-5′-O-(d im eth oxytr ityl)-4′-C-(1-h yd r oxyeth yl)-
a d en osin e (19). A mixture of 17 (204 mg, 0.20 mmol),
Bu3SnH (160 µL, 0.60 mmol), and AIBN (10 mg, 0.06 mmol)
in benzene (2 mL) was stirred at 80 °C for 30 min. The solvent
was evaporated under reduced pressure, and the residue was
partitioned between MeCN and hexane. The MeCN layer was
evaporated under reduced pressure. A mixture of the residue,
aqueous H2O2 (30%, 112 µL, 1.0 mmol), KF (60 mg, 1.0 mmol),
and KHCO3 (32 mg, 0.32 mmol) in MeOH/THF (1:1, 6 mL)
was stirred at room temperature for 15 h. Aqueous Na2S2O3
(1 M, 20 mL) was added, and the resulting insoluble materials
were filtered off. The filtrate was evaporated under reduced
pressure, and the residue was purified by column chromatog-
raphy (SiO2, 8% MeOH in CHCl3) to give 19 (118 mg, 98%) as
a syrup: 1H NMR (500 MHz, CDCl3), δ 8.21 (s, minor H-8),
8.13 (s, major H-8), 7.77 (s, minor H-2), 7.76 (s, major H-2),
7.39-6.82 (m, major and minor Ph), 6.43 (m, major and minor
H-1′), 5.69 (br s, major and minor NH2), 4.97 (m, minor H-3′),
4.81 (d, major H-3′, J ) 4.8), 4.42 (q, minor H-6′, J ) 6.6),
4.21 (q, major H-6′, J ) 6.6), 3.78 (s, major and minor OMe),
3.63 (d, major H-5′a, J ) 10.0), 3.42 (d, major H-5′b, J ) 10.0),
3.31 (d, minor H-5′, J ) 9.6), 3.18 (d, minor H-5′b, J ) 9.6),
3.03 (m, major H-2′a), 2.94 (m, minor H-2′a), 2.59 (m, minor
H-2′b), 2.48 (m, major H-2′b), 1.15 (d, major and minor H-7′ J
) 6.6), the assignments were in agreement with COSY
spectrum, and the ratio of major and minor diastereomers was
C
33H35DO6N5Si 599.2727, found 599.2717.
5′-O-(ter t-Bu tyld im eth ylsilyl)-2′-d eoxy-4-C-(1-h yd r oxy-
eth yl)a d en osin e (22). A mixture of 19 (260 mg, 0.44 mmol)
and BzCl (400 µL, 4.4 mmol) in pyridine (5 mL) was stirred at
room temperature for 15 h. After MeOH was added, the
resulting mixture was evaporated under reduced pressure, and
the residue was partitioned between EtOAc and H2O. The
organic layer was washed with brine, dried (Na2SO4), and
evaporated under reduced pressure. A solution of the residue
and TFA (170 µL, 2.2 mmol) in CH2Cl2 (10 mL) was stirred at
room temperature for 2 h, aqueous NaHCO3 (saturated, 10
mL) was added, and the resulting mixture was partitioned.
The organic layer was washed with brine, dried (Na2SO4), and
evaporated under reduced pressure. The resulting residue,
imidazole (177 mg, 2.6 mmol), and TBSCl (200 mg, 1.3 mmol)
were dissolved in DMF (5 mL), and the resulting mixture was
stirred at room temperature for 15 h. After MeOH was added,
the resulting mixture was evaporated under reduced pressure,
and the residue was partitioned between EtOAc and H2O. The
organic layer was washed with brine (10 mL), dried (Na2SO4),
and evaporated under reduced pressure. To the solution of
the residue in MeOH (10 mL) was added NaOMe (5.2 M in
MeOH, 85 µL, 0.44 mmol), and the resulting mixture was
2:1; HRMS (FAB) calcd for
C33H36N5O6 598.2664, found
598.2696. Similar reaction of 17 (102 mg, 0.10 mmol) with
Bu3SnD, instead of Bu3SnH, gave deuterium-labeled 26 (55
mg, 50%): HRMS (FAB) calcd for C33H35DN5O6 599.2727,
found 599.2733.

754 J . Org. Chem., Vol. 63, No. 3, 1998
Shuto et al.
stirred at room temperature for 15 h. The mixture was
neutralized with AcOH and then evaporated. The residue was
purified by column chromatography (SiO2, 8% MeOH in
CHCl3) to give 22 (98 mg, 54%) as a foam: 1H NMR (500 MHz,
CDCl3) δ 8.33 (s, minor), 8.31 (s, major), 8.00 (s, minor), 7.91
(s, major), 6.50 (dd, minor, J ) 7.0, 6.6), 6.43 (dd, major, J )
9.4, 5.5), 5.61 (br s, major and minor), 4.89 (d, minor, J ) 3.4),
4.76 (d, major, J ) 5.1), 4.28 (q, minor, J ) 6.6), 4.15 (q, major,
J ) 6.6), 4.03 (d, minor, J ) 10.5), 3.88 (d, major, J ) 10.0),
3.74 (d, minor, J ) 10.5 Hz), 3.62 (d, major, J ) 10.0), 3.31
(m, major), 3.00 (m, minor), 2.60 (ddd, minor, J ) 13.6, 6.6,
3.4), 2.51 (ddd, major, J ) 13.7, 5.5, 5.1), 1.36 (d, major, J )
6.6), 1.33 (d, minor, J ) 6.6), 0.92 (s, minor), 0.94 (s, major),
0.16, 0.15 (each s, major), 0.11, 0.09 (each s, minor), the ratio
of major and minor diastereomers were about 2:1; HRMS (EI)
calcd for C18H31N5O4Si 409.2143, found 409.2136.
Aceton id es 23a a n d 23b. A mixture of 22 (79 mg, 0.20
mmol), dimethoxypropane (74 µL, 0.57 mmol), and PPTS (33
mg, 0.13 mmol) in acetone (3 mL) was stirred at room
temperature for 3 days. The resulting solution was evaporated
under reduced pressure, and the residue was partitioned
between EtOAc and H2O. The organic layer was washed with
brine, dried (Na2SO4), and evaporated under reduced pressure.
The residue was purified by column chromatography (SiO2,
4% MeOH in CHCl3) to give 23a (18 mg, 21%) and 23b (6 mg,
7%) in pure forms, respectively. 23a : 1H NMR (500 MHz,
CDCl3) δ 8.36 (s, 1 H, H-8), 8.22 (s, 1 H, H-2), 6.66 (dd, 1 H,
H-1′, J ) 7.4, 7.4), 5.68 (br s, 2 H, NH2), 4.44 (dd, 1 H, H-3′, J
) 3.0, 3.0), 3.93 (m, 2 H, H-5′a and 4′-CH(OH)CH3), 3.78 (d, 1
H, H-5′b, J ) 10.7), 2.54 (m, 2 H, H-2′ab), 1.39, 1.37 (each s,
each 3 H, Me), 1.13 (d, 3 H, 4′-CHCH3, J ) 6.8), 0.96 (s, 9 H,
t-Bu), 0.16, 0.15 (each s, each 3 H, Me), the assignments were
in agreement with COSY spectrum; HRMS (EI) calcd for
C21H35O4N5Si 449.2459, found 449.2472. 23b: 1H NMR (500
MHz, CDCl3) δ 8.32 (s, 1 H, H-8), 7.92 (s, 1 H, H-2), 6.43 (dd,
1 H, H-1′, J ) 9.5, 5.6), 5.58 (br s, 2 H, NH2), 4.76 (d, 1 H,
H-3′, J ) 3.8), 4.41 (q, 1 H, 4′-CHCH3, J ) 6.4), 4.19 (d, 1H,
H-5′a, J ) 10.8), 3.57 (ddd, 1 H, H-2′a, J ) 13.6, 9.5, 3.8), 3.48
(d, 1 H, H-5′b, J ) 10.8), 2.37 (dd, 1 H, H-2′b, J ) 13.6, 5.6),
1.53, 1.45 (each s, each 3 H, Me), 1.24 (d, 3 H, 4′-CHCH3, J )
6.4), 0.94 (s, 9 H, t-Bu), 0.14, 0.11 (each s, each 3 H, Me), the
assignments were in agreement with COSY spectrum; HRMS
(EI) calcd for C21H35O4N5Si (M+ - t-Bu) 392.1754, found
392.1777.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR, HMBC,
and NOESY spectral charts of 12, 1H NMR and NOESY
1
spectral charts of 23a , and H NMR spectral charts of 19, 21,
26, and 27 (9 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O971703A