Efficient bis-C-aminoglycosylation toward the synthesis of the pluramycins

Article abstract of DOI:10.1055/s-0030-1258766

Two bis-C-aminoglycosyl arenes containing the angolosamine and the vancosamine moieties, which are potentially useful as the D-ring fragments of the pluramycin-type antibiotics, were efficiently synthesized by the OC-glycoside rearrangement based strategy

Full text of DOI:10.1055/s-0030-1258766

2654
LETTER
Efficient Bis-C-Aminoglycosylation toward the Synthesis of the Pluramycins
Efficient
B
is-C-Amino
a
glycosylati
s
on toward
a
the Synthe
y
sis of the Plu
u
ramycins ki Shigeta,a,b Tomohiko Hakamata,a,b Yukie Watanabe,a,b Kei Kitamura,a,b Yoshio Ando,a,b
Keisuke Suzuki,*a,b Takashi Matsumoto*b,c
a
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro, Tokyo, 152-8551, Japan
Japan Science and Technology Agency (JST), SORST, O-okayama, Meguro, Tokyo, 152-8551, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo, 192-0392, Japan
b
c
Fax +81(42)6763257; E-mail: tmatsumo@toyaku.ac.jp
Received 4 August 2010
structing bis-C-glycosyl arene structure by performing the
Abstract: Two bis-C-aminoglycosyl arenes containing the an-
O→C-glycoside rearrangement twice on a resorcinol de-
golosamine and the vancosamine moieties, which are potentially
useful as the D-ring fragments of the pluramycin-type antibiotics,
rivative (Scheme 1).4 Thus, the next questions to be ad-
dressed were, (1) whether the method would be adapted to
the amino sugar system, and (2) whether the two phenolic
hydroxy groups in the resulting bis-C-glycosyl arene
could be managed to discriminate for the following trans-
formations. Herein, we report that experimentation an-
swered in the affirmative to these questions, thereby
allowing the synthesis of bis-C-aminoglycosides 1 and 2.
They represent the first case of bis-C-glycosyl arenes fur-
nished with both the angolosamine and the vancosamine
moieties. Furthermore armed with the clues to the con-
struction of the polycyclic skeleton, compounds 1 and 2
will serve as the useful D-ring fragments for the pluramy-
cin synthesis.
were efficiently synthesized by the O→C-glycoside rearrangement
based strategy.
Key words: natural product synthesis, pluramycin-type antibiotics,
amino sugar, bis-C-glycoside, O→C-glycoside rearrangement
The pluramycins are a family of antibiotics featured by
4H-anthra[1,2-b]pyran-4,7,12-trione chromophore with
two amino sugars attached through the C-glycosidic link-
ages (Figure 1).1 These compounds exhibit potent antitu-
mor activity by DNA alkylation, where the two proximal
amino sugars, D-angolosamine and N,N-dimethyl-L-van-
cosamine, play a key role in sequence recognition in inter-
calation of the tetracyclic chromophore.2 Although such
biochemical significance as well as the unique structure
has made them attractive synthetic targets, no total syn-
thesis has been recorded thus far.3
O
OH
OH
X
O
R
R
sugar-1
sugar-1
O→C-glycoside
OPG
OPG
rearrangement
(PG = protecting group)
R1
sugar R1
OH
O
OH
D
O
C
O
O
B
O
OH
X
A
O
R
sugar
R
pluramycin A
hedamycin
a
b
b
c
c
A
B
C
C
D
sugar-2
O
sugar-1
sugar-1
OH
OH
O→C-glycoside
(N,N-dimethyl-
L-vancosamine)
rearrangement
kidamycin
O
O
isokidamycin
saptomycin B
sugar-2
(D-angolosamine)
NMe2
HO
OMe
OMe
CO2Me
I
O
O
O
O
sugar:
NCOCF3
BnO
NCOCF3
H
NMe2
NMe2
R2O
HO
BnO
OTf
H
a: R2 = Ac
c
O
O
b: R2 = H
O
NCOCF3
BnO
NCOCF3
BnO
O
H
H
R1:
1
2
O
A
B
C
D
Scheme 1
Figure 1
The synthesis of bis-C-glycoside 1 commenced with the
C-glycosylation of monoprotected resorcylic ester 3.5 An
extensive survey of the reaction conditions by employing
glycosyl acetates 46 and 67 as the vancosamine and the an-
golosamine donors, respectively, proved that the reaction
with 4 cleanly proceeded with Sc(OTf)3 (20 mol%) and
Drierite in dichloroethane4 to afford b-C-glycoside 5 as
the sole product in 88% yield (Scheme 2).8 Predominant
In our efforts toward the synthesis of these natural prod-
ucts, we previously reported an effective method for con-
SYNLETT 2010, No. 17, pp 2654–2658
x
x
.x
x
.2
0
1
0
Advanced online publication: 01.10.2010
DOI: 10.1055/s-0030-1258766; Art ID: U07210ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Efficient Bis-C-Aminoglycosylation toward the Synthesis of the Pluramycins
2655
formation of the b-isomer is ascribable to the thermody- the reaction of 3 with 6 (Scheme 3), where the an-
namic preference, since the possible a-isomer would suf- golosamine moiety in the mono-C-glycoside 7 suffered
fer from significant steric repulsion between the C(6) the two-fold arylation].12
4
methyl and the C(3) amide given the C1 conformation
OH
Sc(OTf)3 (50 mol%)
dictated by the strong tendency of the C(1) aryl moiety to
CO2Me
O
BnO
HN
O
Drierite
+
occupy the equatorial position.9
DCE
25 °C, 1.8 h
97%
NCOCF3
H
OAc
COCF3
BnO
OR
OH
5: R = CH2CH=CH2
6
OAc
Sc(OTf)3 (20 mol%)
Drierite
a
CO2Me
10: R = H
(1.3 equiv)
O
+
DCE
0 °C, 0.5 h
88%
NCOCF3
BnO
O
OH
H
CO2Me
3 (1.7 equiv)
4
O
NCOCF3
H
BnO
OH
OH
O
CO2Me
O
O
NCOCF3
BnO
NCOCF3
BnO
H
H
5
11
Scheme 2
Scheme 4 Reagents and conditions: (a) Pd(OAc)2 (10 mol%), Ph3P
(40 mol%), HCO2H, Et3N, 1,4-dioxane, 60 °C, 15 min, 96%.
The reaction of 3 with angolosaminyl acetate 6 also led to
the desired b-C-glycoside 7 in good yield under the simi-
lar conditions, but along with many by-products
(Scheme 3). Among such by-products, the major one was
identified as the two-fold arylation product 8 (24%), pre-
sumably arising from Lewis acid promoted ring opening
of 7 to generate the quinone methide like intermediate 9
followed by further attack of 3.10
OH
CO2Me
O
NCOCF3
BnO
OH
H
O
NCOCF3
BnO
11
H
OH
a,b
Sc(OTf)3 (30 mol%)
CO2Me
O
BnO
HN
Drierite
+
DCE
0 °C, 5 h
OAc
OTBDPS
OH
COCF3
O
CO2Me
CO2Me
O
O
6
3 (2 equiv)
NCOCF3
H
NCOCF3
H
BnO
BnO
OH
OTBDPS
O
O
O
O
CO2Me
OH
CO2Me
OH
NCOCF3
H
NCOCF3
H
F3COC
BnO
BnO
12
13
NH
+
O
HO
c–e
f–h
OBn
HO
O
OMe
OMe
NCOCF3
H
CO2Me
BnO
CO2Me
OTf
i
CO2Me
O
O
NCOCF3
H
7
55%
8 24%
NCOCF3
H
BnO
BnO
O
O
O
CO2Me
NCOCF3
H
NCOCF3
H
BnO
14
BnO
1
F3COC
+
OH
NH
Scheme 5 Reagents and conditions: (a) NaH, (t-Bu)Ph2SiCl, DMF,
0 °C, 93%; (b) Bu4NF, MS 4A, THF, –30 °C, 89% (12:13 = 3.2:1);
(c) PhNTf2, K2CO3, acetone, 25 °C, quant; (d) Bu4NF, THF, 0 °C,
98%; (e) (MeO)2SO2, K2CO3, acetone, 25 °C, 92%; (f) (MeO)2SO2,
K2CO3, acetone, 25 °C; (g) Bu4NF, THF, 0 °C, 73% (2 steps); (h)
PhNTf2, K2CO3, acetone, 25 °C, 92%; (i) (MeBO)3 (120 mol%),
Pd(PPh3)4 (16 mol%), Cs2CO3 (3.4 equiv), 1,4-dioxane, 100 °C,
89%.
O
(TfO)3Sc–
OBn
9
Scheme 3
Fortunately, however, angolosaminyl acetate 6 worked
nicely in the installation of the second sugar moiety
(Scheme 4). After removal of the allyl group from mono-
C-glycoside 5,11 the resulting diol 10 was smoothly C-gly-
cosylated with angolosaminyl acetate 6 (1.3 equiv) under
the conditions involving Sc(OTf)3 and Drierite to afford
bis-C-glycoside 11 in 97% yield with no trace of the two-
fold arylation. This result implied that the susceptibility of
the angolosamine moiety to the two-fold arylation was re-
duced in 11 by the co-existing C-glycoside moiety [see
Conversion of bis-C-glycoside 11 into the target interme-
diate 1 was fairly effective, even if not very straightfor-
ward (Scheme 5). Since it was apparent that the two
hydroxy groups in 11 were similar in their reactivity, we
once protected both with tert-butyldiphenylsilyl groups,
and examined monodesilylation of the resulting bissilyl
ether. Fortunately, use of Bu4NF under the controlled con-
Synlett 2010, No. 17, 2654–2658 © Thieme Stuttgart · New York

2656
M. Shigeta et al.
LETTER
ditions afforded a mixture of the monosilyl ethers, 12 and ploying Sc(OTf)3 and Drierite in the first C-glycosylation
13, in high yield, which were easily separable by silica gel of 15 and also in the second C-glycoside formation after
chromatography.13 Each isomer converged into triflate 14 desilylation.18,19 Conversion of diol 18 to o-iodo triflate 2
in high overall yield through the three-step sequence in- was accomplished by utilizing again the bissilylation–
cluding triflation (PhNTf2, K2CO3, acetone),14 desilyla- monodesilylation sequence in high
overall yield
tion (Bu4NF, THF), and methyl ether formation (Scheme 8).13
[(MeO)2SO2, K2CO3, acetone], in this order (for the iso-
mer 12) or the reverse order (for the isomer 13). Finally,
OH
I
O
triflate 14, upon reaction with trimethylboroxine under the
NCOCF3
BnO
OH
Pd(0)-catalyzed conditions,15 led to the desired bis-C-gly-
H
O
cosylated o-toluate 1 in 89% yield.
Providing that the Staunton–Weinreb annulation16 [i.e.,
NCOCF3
BnO
18
H
the condensation of o-toluate-derived benzylic anion with
Michael acceptors (Scheme 6)] tolerates the sugar moi-
eties as the substituents, bis-C-glycoside 1 would be
promising as the intermediate toward the construction of
the polycyclic framework of the pluramycins.
a,b
OSi(i-Pr)3
I
OH
I
O
O
NCOCF3
H
NCOCF3
H
BnO
BnO
OH
OSi(i-Pr)3
O
OH
O
CO2R1
O
O
+
X
R2
R2
NCOCF3
H
NCOCF3
H
BnO
BnO
f–h
21
c–e
22
Scheme 6 The Staunton–Weinreb annulation
OMe
OH
OMe
I
O
I
O
OAc
NCOCF3
O
BnO
BnO
O
OTBDPS
NCOCF3
H
HN
H
BnO
a
OTf
d
15
NCOCF3
OAc
O
COCF3
BnO
H
O
4
6
OR
NCOCF3
H
BnO
I
NCOCF3
H
BnO
OH
23
OH
2
I
O
O
NCOCF3
H
Scheme 8 Reagents and conditions: (a) NaH, (i-Pr)3SiCl, DMF, 0
°C, 92%; (b) Bu4NF, MS 4A, THF, 0 °C, 87% (21:22 = 1.7:1); (c)
PhNTf2, K2CO3, acetone, 25 °C, 99%; (d) Bu4NF, THF, 0 °C, 89%;
(e) (MeO)2SO2, K2CO3, acetone, 25 °C, 83%; (f) (MeO)2SO2, K2CO3,
acetone, 25 °C, 97%; (g) Bu4NF, THF, 0 °C, 86%; (h) PhNTf2,
K2CO3, acetone, 25 °C, 97%.
BnO
OR
NCOCF3
H
19: R = TBDPS
20: R = H
16: R = TBDPS
17: R = H
b
BnO
e
OAc
O
BnO
HN
O
OH
I
c
f
OAc
NCOCF3
BnO
COCF3
O
Compound 2, thus obtained, could serve as the precursor
of benzyne 23, thereby allowing application to various cy-
cloaddition reactions.20
H
6
4
NCOCF3
H
BnO
OH
O
In summary, the bis-C-glycoside synthesis based on the
O→C-glycoside rearrangement was successfully applied
to the amino sugar system to allow efficient access to the
bis-C-aminoglycosides 1 and 2, which contain the an-
golosamine and the vancosamine moieties and also the
key clues to further elaboration of the aromatic ring. Fur-
ther studies toward the total synthesis of the pluramycins
are now underway in this laboratory.
NCOCF3
H
BnO
18
Scheme 7 Reagents and conditions: (a) 4 (1 equiv), 15 (1.9 equiv),
Sc(OTf)3 (30 mol%), Drierite, DCE, 0 °C, 8 h, 81%; (b) Bu4NF, THF,
25 °C, 98%; (c) 6 (1.7 equiv), Sc(OTf)3 (25 mol%), Drierite, DCE, 25
°C, 6 h, 77%; (d) 6 (1 equiv), 15 (2 equiv), Sc(OTf)3 (25 mol%), Dri-
erite, DCE, 0 °C, 5 h, 93%; (e) Bu4NF, THF, 25 °C, 92%; (f) 4 (1.3
equiv), Sc(OTf)3 (25 mol%), Drierite, DCE, 15 °C, 7 h, 80%.
Supporting Information for this article is available online at
ortho-Iodophenyl triflate 2, the other target intermediate
of ours, was synthesized in a similar way starting from
monoprotected 2-iodoresorcinol 1517 (Scheme 7). In this
synthesis, the order of the amino sugar installation did not
make considerable difference to its efficiency. Both of the
glycosyl donors worked nicely under the conditions em-
http://www.thieme-connect.com/ejournals/toc/synlett.
References and Notes
(1) For the first isolation, see: (a) Maeda, K.; Takeuchi, T.;
Nitta, K.; Yagishita, K.; Utahara, R.; Osato, T.; Ueda, M.;
Synlett 2010, No. 17, 2654–2658 © Thieme Stuttgart · New York

LETTER
Efficient Bis-C-Aminoglycosylation toward the Synthesis of the Pluramycins
2657
Kondo, S.; Okami, Y.; Umezawa, H. J. Antibiot., Ser. A
(8) The anomeric configurations in 5 and 11 (Figure 2) were
determined by the coupling constants of 1H NMR spectra
and NOE measurements. For details, see Supporting
Information.
1956, 9, 75. (b) For the first structure determination, see:
Furukawa, M.; Hayakawa, I.; Ohta, G.; Iitaka, Y.
Tetrahedron 1975, 31, 2989. For reviews, see: (c) Séquin,
U. Fortschr. Chem. Org. Naturst. 1986, 50, 57. (d) Bililign,
T.; Griffith, B.; Thorson, J. Nat. Prod. Rep. 2005, 22, 742.
(2) For reviews, see: (a) Hansen, M. R.; Hurley, L. H. Acc.
Chem. Res. 1996, 29, 249. (b) Willis, B.; Arya, D. P. Curr.
Org. Chem. 2006, 10, 663.
(3) For synthetic studies, see: (a) Parker, K. A.; Koh, Y.-H.
J. Am. Chem. Soc. 1994, 116, 11149. (b) Parker, K. A.; Su,
D.-S. J. Carbohydr. Chem. 2005, 24, 199. (c) Kaclin, D. E.
Jr.; Lopez, O. D.; Martin, S. F. J. Am. Chem. Soc. 2001, 123,
6937. (d) Martin, S. F. Pure Appl. Chem. 2003, 75, 63.
(e) Fei, Z.; McDonald, F. E. Org. Lett. 2007, 9, 3547.
(4) (a) Yamauchi, T.; Watanabe, Y.; Suzuki, K.; Matsumoto, T.
Synlett 2006, 399. (b) Yamauchi, T.; Watanabe, Y.; Suzuki,
K.; Matsumoto, T. Synthesis 2006, 2818. For the O→C-
glycoside rearrangement, see: (c) Matsumoto, T.; Katsuki,
M.; Suzuki, K. Tetrahedron Lett. 1988, 29, 6935.
(d) Matsumoto, T.; Hosoya, T.; Suzuki, K. Synlett 1991,
709. (e) Ben, A.; Yamauchi, T.; Matsumoto, T.; Suzuki, K.
Synlett 2004, 225.
4.00 (q, J = 6.4 Hz)
4.94 (dd, J = 2.0, 11.6 Hz)
H
H
OH
CO2Me
O
O
NCOCF3
H
BnO
5
4.00 (q, J = 6.4 Hz)
4.86 (dd, J = 1.8, 12.2 Hz)
H
H
OH
CO2Me
O
NCOCF3
H
BnO
OH
O
H
NOE:
4.77
(in CDCl3)
(dd, J = 2.0,11.2 Hz)
NCOCF3
H
BnO
11
(5) Resorcylic ester 3 was synthesized as shown below (Scheme
9). For the preparation of the intermediate 24, see: Hadfield,
A.; Schweitzer, H.; Trova, M. P.; Green, K. Synth. Commun.
1994, 24, 1025.
Figure 2
(9) (a) Hosoya, T.; Ohashi, Y.; Matsumoto, T.; Suzuki, K.
Tetrahedron Lett. 1996, 37, 663. (b) Also see reference 4e.
(10) It is interesting to note that vancosaminyl acetate 4 upon
reaction with excess resorcylic ester 29 (3 molar amounts)
gave mono-C-glycoside 10 and bis-C-glycoside 30 in high
combined yield without formation of the two-fold arylation
product (Scheme 12). In contrast, the reaction of
OH
OH
O
O
CO2H
OH
CO2Me
O
a, b
O
OH
angolosaminyl acetate 6 with 29 (2 molar amounts) gave
none of the bis-C-glycoside but yielded mono-C-glycoside
31 (28% yield), the two-fold arylation product 32 (12%), and
many other unidentified products of higher molecular
weights. It is therefore obvious that the angolosamine moiety
is much more apt to undergo the two-fold arylation, as
compared with the vancosamine moiety. We surmise the
steric congestion at the C(3) position in the vancosamine
moiety makes it resistant to this unfavorable reaction.
24
3
Scheme 9 Reagents and conditions: (a) CH2=CHCH2Br, K2CO3,
acetone; (b) K2CO3, MeOH, 93% (2 steps).
(6) Vancosaminyl acetate 4 was synthesized as shown below
(Scheme 10). (a) For the preparation of the intermediate 25,
see: Hsu, D.-S.; Matsumoto, T.; Suzuki, K. Synlett 2006,
469. (b) For the selective alcoholysis of a benzoate by using
Mg(OMe)2, see: Xu, Y.-C.; Bizuneh, A.; Walker, C.
Tetrahedron Lett. 1996, 37, 455.
OH
OH
CO2Me
OH
CO2Me
OH
O
O
a
4
+
NCOCF3
H
NCOCF3
H
BnO
BnO
HO
HO
HO
OH
O
O
OMe
O
OMe
a, b
c, d
10
72%
30 26%
4
O
H
NCOCF3
NCOCF3
OMe
BzO
BnO
N
COCF3
H
H
O
25
26
Bn
OH
OH
Scheme 10 Reagents and conditions: (a) Mg(OMe)2, MeOH, 25
°C, 70%; (b) NaH, BnBr, DMF, 0 °C, 83%; (c) 20% AcOH, 100 °C;
(d) Ac2O, 4-DMAP, pyridine, 92% (2 steps).
CO2Me
CO2Me
OH
b
6
+
F3COC
OH
NH
O
HO
(7) Angolosaminyl acetate 6 was synthesized as shown below
(Scheme 11). For the preparation of the intermediate 27, see:
Bartner, P.; Boxler, D. L.; Brambilla, R.; Mallams, A. K.;
Morton, J. B.; Reichert, P.; Sancilio, F. D.; Surprenant, H.;
Tomalesky, G. J. Chem. Soc., Perkin Trans. 1 1979, 1600.
OH
OBn
CO2Me
OH
HO
OH
CO2Me
NCOCF3
H
BnO
29
31
28%
32 12%
Scheme 12 Reagents and conditions: (a) 29 (3 equiv), Sc(OTf)3 (25
mol%), Drierite, DCE, 5 °C, 2 h; (b) 29 (2 equiv), Sc(OTf)3 (25
mol%), Drierite, DCE, 0 °C, 23 h.
HO
HO
HO
OH
O
O
O
a
HO
N3
BnO
N3
b–d
6
OMe
OMe
OMe
(11) Hey, H.; Arpe, H.-J. Angew. Chem., Int. Ed. Engl. 1973, 12,
928.
27
28
Scheme 11 Reagents and conditions: (a) NaH, BnBr, DMF, 92%;
(b) Ph3P, CH2Cl2 then (CF3CO)2O, Et3N, 83%; (c) 20% AcOH, 100 °C;
(d) Ac2O, 4-DMAP, pyridine, 83% (2 steps).
(12) Actually, treatment of bis-C-glycoside 11 with excess
amounts of diol 29 under the Sc(OTf)3–Drierite conditions
led to the complete recovery of 11 (Scheme 13).
Synlett 2010, No. 17, 2654–2658 © Thieme Stuttgart · New York

2658
M. Shigeta et al.
LETTER
3.96 (q, J = 6.4 Hz)
OH
4.58 (dd, J = 2.3, 12.4 Hz)
OH
CO2Me
OH
CO2Me
O
H
H
OH
I
NCOCF3
H
O
BnO
29 (2 equiv)
OH
no reaction
NCOCF3
H
Sc(OTf)3 (150 mol%)
Drierite
O
BnO
OTBDPS
DCE
25 °C, 3 d
16
NCOCF3
H
BnO
4.00 (q, J = 6.3 Hz)
4.65 (dd, J = 2.8, 12.0 Hz)
11
H
H
OH
I
Scheme 13
O
(13) For determination of the regiochemistry, see Supporting
Information.
NCOCF3
H
BnO
OH
(14) Hendrickson, J. M.; Bergeron, R. Tetrahedron Lett. 1973,
14, 4607.
O
H
NOE:
4.69
(15) (a) Gray, M.; Andrews, I. P.; Hook, D. F.; Kitteringham, J.;
Voyle, M. Tetrahedron Lett. 2000, 41, 6237. (b) For a
review on the Suzuki–Miyaura reaction, see: Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457.
(dd, J = 2.1,11.6 Hz)
(in CDCl3)
NCOCF3
H
BnO
18
Figure 3
(16) (a) Leeper, F. J.; Staunton, J. J. Chem. Soc., Chem. Commun.
1978, 406. (b) Dodd, J. H.; Weinreb, S. M. Tetrahedron
Lett. 1979, 20, 3593. (c) Leeper, F. J.; Staunton, J. J. Chem.
Soc., Perkin Trans. 1 1984, 1053. For recent applications
to natural product synthesis, see: (d) Donner, C. D.
Tetrahedron Lett. 2007, 48, 8888. (e) Sperry, J.; Brimble,
M. A. Synlett 2008, 1910.
(17) Iodoresorcinol 15 was synthesized as shown below
(Scheme 14). For the preparation of the intermediate 33,
see: (a) Hamura, T.; Hosoya, T.; Yamaguchi, H.; Kuriyama,
Y.; Tanabe, M.; Miyamoto, M.; Yasui, Y.; Matsumoto, T.;
Suzuki, K. Helv. Chim. Acta 2002, 85, 3589. (b)Tsujiyama,
S.; Suzuki, K. Org. Synth. 2007, 84, 272.
OH
OR
CO2Me
OH
I
OH
29 (2 equiv)
no reaction
O
Sc(OTf)3 (150 mol%)
Drierite
DCE
25 °C, 3 d
NCOCF3
H
BnO
19: R = TBDPS
20: R = H
Scheme 15
under the conditions with excess Sc(OTf)3 (Scheme 15).
These results, setting the reason aside, imply that
susceptibility of the C-glycoside moiety to the two-fold
arylation depends on the C(2)-substituent of the resorcinol
moiety, in addition to the structure of the sugar moiety as
described in reference 10.
OH
OH
OBz
I
I
a, b
OH
OTBDPS
OH
33
15
(20) (a) Matsumoto, T.; Hosoya, T.; Katsuki, M.; Suzuki, K.
Tetrahedron Lett. 1991, 32, 6735. (b) For the generation
and cycloadditions of the benzynes containing C-glycoside
moieties, see: Matsumoto, T.; Hosoya, T.; Suzuki, K. J. Am.
Chem. Soc. 1992, 114, 3568. (c) Matsumoto, T.;
Yamaguchi, H.; Suzuki, K. Tetrahedron 1997, 53, 16533.
(d) Futagami, S.; Ohashi, Y.; Imura, K.; Hosoya, T.;
Ohmori, K.; Matsumoto, T.; Suzuki, K. Tetrahedron Lett.
2000, 41, 1063. (e) Matsumoto, T.; Yamaguchi, H.;
Hamura, T.; Tanabe, M.; Kuriyama, Y.; Suzuki, K.
Tetrahedron Lett. 2000, 41, 8383.
Scheme 14 Reagents and conditions: (a) (t-Bu)Ph2SiCl, imidazole,
DMF, 93%; (b) Me2N(CH2)3NH2, Et3N, THF, 95%.
(18) The anomeric configurations in 16 and 18 (Figure 3) were
determined by the coupling constants of 1H NMR and NOE
measurements. For details, see Supporting Information.
(19) So far, we have never encountered the two-fold arylation in
the C-glycosylation of various 2-iodoresorcinol derivatives,
regardless of the glycosyl donors (see references 4, 20b–d).
Furthermore, it turned out that mono-C-glycosides 19 and 20
possessing the angolosamine moieties were recovered intact
even after treatment with two molar amounts of diol 29
Synlett 2010, No. 17, 2654–2658 © Thieme Stuttgart · New York

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