C-glycosylation via radical cyclization: Synthetic application to a new C-glycoside

Article abstract of DOI:10.1016/S0040-4039(99)02011-0

Radical cyclization of ribo-phenylselenoglycoside tethered with propargyl moieties on C-5 hydroxyl group afforded new potential intermediates for the synthesis of C-nucleoside derivatives.

Full text of DOI:10.1016/S0040-4039(99)02011-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 225–227
C-Glycosylation via radical cyclization: synthetic application to
a new C-glycoside
∗
Guncheol Kim and Hee Seok Kim
Department of Chemistry, College of Natural Sciences, Chungnam National University, Taejon 305-764, South Korea
Received 13 September 1999; revised 18 October 1999; accepted 22 October 1999
Abstract
Radical cyclization of ribo-phenylselenoglycoside tethered with propargyl moieties on C-5 hydroxyl group
afforded new potential intermediates for the synthesis of C-nucleside derivatives. © 1999 Elsevier Science Ltd.
All rights reserved.
New routes to C-glycosides have been developed over recent years due to their structural attraction
1
as well as useful biological activities. Most of the approaches have concerned the stereoselective C-
glycosylation reaction at the first stage. Several selective methods involving connecting the necessary
functional groups to the adjacent one such as an alcohol have been explored recently and proved to be
2
an insured way to achieve the desired stereochemistry. In this paper, we report a new radical cyclization
reaction of phenylselenofuranoside tethered with propargyl moieties on C-5 hydroxyl group and a
synthetic application. After the cyclization reaction, the carbon–oxygen bond of the tether is expected
to be oxidatively cleaved for further manipulation (Scheme 1).
Scheme 1.
Propargyl intermediates 2 have been prepared by using the known intermediate 12d via a two-step
sequence, treating with propargyl bromide/NaH and deprotonation with n-BuLi followed by addition of
electrophiles such as TMSCl or MeI, providing 2a or 2b with the same yield of 78% in two steps. Under
the conventional radical reaction condition, Bu SnH/AIBN in toluene (80°C), 2 afforded the desired
3
3
products, 93% for 3a and 82% for 3b, respectively. The radical cyclization of propagyl ether without
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02011-0
tetl 15939

2
26
TMS or methyl protecting groups of 2 suffered from low yield due to competative hydrostannylation of
the triple bond.
Allylic oxidation of 3 with SeO in 1,4-dioxane in the presence of acetic acid gave out aldehyde 4
2
(
29% for 4a and 69% for 4b) presumably through hemiacetal intermediate (Scheme 2). When treated
4
with pyridinium dichromate in DMF, the aldehydes 4 were further oxidized to lactones 5 (30% and
7
the known precursor of showdomycin syntheses, under ozonolysis and reductive cleavage.
5
4%, respectively), through hemiacetal intermediate also, which could be converted to 6 in 19% yield,
6
Scheme 2.
Transformation of the aldehyde intermediates 4 to a pyrazine C-glycoside derivative was performed
by ozonolysis and reductive cleavage to yield α-keto aldehyde intermediate, which was reacted with 1,2-
4
phenylenediamine without purification. Compound 7 was obtained in 21% yield from 4a and 52% from
4
4
b, respectively. Deprotection of 7 in a 4:1 mixture of CF CO H and H O provided 8 in 41% yield.
3
2
2
In summary, the radical cyclization reaction of ribofuranose intermediate 2 suggests a new C-
glycosylation route for C-glycoside derivatives.
Acknowledgements
This research was financially supported by the Ministry of Education through the Basic Science
Research Institute Program (BSRI-98-3433).
References
1
2
. Jaramillo, C.; Knapp, S. Synthesis 1994, 1–20. (b) Postema, M. H. D. C-Glycoside Synthesis; CRC Press: Boca Raton, 1995.
. Yahiro, Y.; Ichikawa, S.; Shuto, S.; Matsuda, A. Tetrahedron Lett. 1999, 40, 5527–5531. (b) De Mesmaeker, A.; Waldner, A.;
Hoffmann, P.; Winkler, T. Synlett 1994, 330–332. (c) Kim, G.; Kang, S.; Kim, S. N. Tetrahedron Lett. 1993, 37, 7627–7628.
(d) Stork, G.; Suh, H. S.; Kim, G. J. Am. Chem. Soc. 1991, 113, 7054–7055.
3
4
. The products are mixtures of E/Z isomers in a ca. 1:1 to 4:3 ratio. Following reactions were carried out with the mixtures.
−
1 1
. Compound 5a (one isomer): IR (CDCl
3
) 1732, 1379, 1371,1251 cm ; H NMR (300 MHz, CDCl
3
) 6.49 (s, 1H), 4.91 (d,
1
9
H, J=5.7 Hz), 4.65 (d, 1H, J=5.7 Hz), 4.55 (s, 1H), 4.37 (m, 1H), 4.15–4.21 (m, 2H), 1.49 (s, 3H), 1.30 (s, 3H), 0.14 (s,
13
H); C NMR (75 MHz, CDCl
3
) 169.1, 151.3, 146.3, 112.3, 87.4, 83.4, 81.8, 81.5, 71.5, 25.9, 24.2, −1.2 (×3); m/z 283
). 7: H NMR (300 MHz, CDCl ) 8.91 (s, 1H), 8.02–8.16 (m, 2H), 7.75–7.83 (m, 2H), 5.38 (d, 1H, J=3.4 Hz),
.92–4.98 (m, 2H), 4.56 (dt, 1H, J=2.4, 2.3 Hz), 4.04 (dd, J=12.4, 2.4 Hz), 3.75 (dd, 1H, J=12.4, 2.7 Hz), 1.60 (s, 3H), 1.40
+
1
(
4
M −CH
3
3
+
25
1
(
8
s, 3H); m/z 287 (M −CH
3
); [α]
D
3
=−7.89 (c=0.015, MeOH). Compound 8: H NMR (400 MHz, CD OD) 9.12 (s, 1H),
.07–8.10 (m, 2H), 7.81–7.87 (m, 2H), 5.10 (d, 1H, J=5.6 Hz), 4.31 (dd, 1H, J=5.6, 5.2 Hz), 4.20 (dd, 1H, J=5.20, 5.20 Hz),

2
27
+
O); [α]
D
25=5.48 (c=0.006,
4
.13 (m, 1H), 3.91 (dd, 1H, J=12.0, 3.2 Hz), 3.77 (dd, 1H, J=12.0, 3.0 Hz); m/z 226 (M −2H
2
MeOH).
5
6
. Every protection condition of the hydroxyl group of 4 provided acetal intermediates. It is assumed that hemiacetal formation
is dominated in the presence of base due to proximity between hydroxyl and aldehyde groups, although the groups exist
separated in neutral condition.
. Noyori, R.; Sato, T.; Hayakawa, Y. J. Am. Chem. Soc. 1978, 100, 2561–2563. The unstable intermediate was confirmed by
−1
NMR showing no vinyl methyl group and IR (1745 cm , C_O) as described in the reference.