Furanodictine A and B: Amino sugar analogues produced by cellular slime mold Dictyostelium discoideum showing neuronal differentiation activity

Article abstract of DOI:10.1021/jo015657x

We investigated the constituents of Dictyostelium discoideum to clarify the diversity of secondary metabolites of Dictyostelium cellular slime molds and to explore biologically active substances that could be useful in the development of novel drugs. From a methanol extract of the multicellular fruit body of D. discoideum, we isolated two novel amino sugar analogues, furanodictine A (1) and B (2). They are the first 3,6-anhydrosugars to be isolated from natural sources. Their relative structures were elucidated by spectral means, and the absolute configurations were confirmed by asymmetric syntheses of 1 and 2. These furanodictines potently induce neuronal differentiation of rat pheochromocytoma (PC-12) cells.

Full text of DOI:10.1021/jo015657x

6982
J . Org. Chem. 2001, 66, 6982-6987
F u r a n od ictin e A a n d B: Am in o Su ga r An a logu es P r od u ced by
Cellu la r Slim e Mold Dictyosteliu m d iscoid eu m Sh ow in g Neu r on a l
Differ en tia tion Activity
Haruhisa Kikuchi,† Yoshinori Saito,† J un Komiya,† Yoshiaki Takaya,† Shigeyoshi Honma,†
Norimichi Nakahata,† Akira Ito,‡ and Yoshiteru Oshima*,†
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578,
J apan, and Kyorin Pharmaceutical Co., Ltd., 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, J apan
oshima@mail.pharm.tohoku.ac.jp
Received April 2, 2001
We investigated the constituents of Dictyostelium discoideum to clarify the diversity of secondary
metabolites of Dictyostelium cellular slime molds and to explore biologically active substances that
could be useful in the development of novel drugs. From a methanol extract of the multicellular
fruit body of D. discoideum, we isolated two novel amino sugar analogues, furanodictine A (1) and
B (2). They are the first 3,6-anhydrosugars to be isolated from natural sources. Their relative
structures were elucidated by spectral means, and the absolute configurations were confirmed by
asymmetric syntheses of 1 and 2. These furanodictines potently induce neuronal differentiation of
rat pheochromocytoma (PC-12) cells.
In tr od u ction
was also isolated as an antibacterial substance.6 The
chemical characteristics of cellular slime molds, however,
remained uncertain. Recently, we have studied the
secondary metabolites produced by cellular slime molds
to explore their diversity as well as their physiological
and pharmacological activities. Our investigation is lead-
ing to the utilization of cellular slime molds as a resource
in novel drug development. We have isolated R-pyronoids
and aromatics with unique structures,7,8 which have
demonstrated physiologically important activities such
as control in cellular slime mold development.8 In this
paper, we outline the elucidation of the structure and the
syntheses of two novel amino sugar analogues, furano-
dictine A (1) and B (2), as well as their ability to induce
neurite outgrowth in rat pheochromocytoma (PC-12)
cells.
Cellular slime molds are unique organisms with a two-
stage life cycle: a unicellular animal-like feeding stage
(a vegetative amoeba stage) and a multicellular plantlike
fruit body stage (a reproductive fruit body stage). Spore
germination produces unicellular amoebae that feed on
bacteria, and when the amoebae starve, they aggregate
by chemotaxis to relayed cyclic AMP signals to form fruit
bodies consisting of spores and a multicellular stalk.
Because of their unique characteristics, cellular slime
molds are frequently used in biological studies of multi-
cellular development.1
Differentiation-inducing factors (DIFs),2 discadenine,3
and several other compounds have been reported as the
growth-regulating metabolites of the cellular slime molds.
Recently, DIF-1 was found to inhibit proliferation and
induce differentiation in mammalian cells, including
murine erythroleukemia (B8) and human leukemia (K562)
cell lines.4 Furthermore, the intriguing experimental
result suggesting that DIF-1 may induce differentiation
of vascular smooth muscle cells in vitro could lead to
novel strategies for the treatment of vascular diseases.5
A chlorine-substituted aromatic compound, AB0022A,
Resu lts a n d Discu ssion
Isola tion a n d Str u ctu r e Elu cid a tion . The fruit
bodies of the cellular slime mold, Dictyostelium discoi-
deum, were cultured on plates (wet wt, 109 g). They were
extracted twice with methanol at room temperature to
yield the extract (5.6 g), which was partitioned with ethyl
acetate and water. The ethyl acetate soluble fraction (1.1
g) was separated by conventional column chromatogra-
phy over silica gel and ODS to yield 1 (1.9 mg) and 2
(2.8 mg).
* To whom correspondence should be addressed. Phone: +81-22-
217-6822. Fax: +81-22-217-6821.
† Tohoku University.
‡ Kyorin Pharmaceutical Co., Ltd.
(1) Dictyostelium A Model System for Cell and Developmental
Biology; Maeda, Y., Inouye, K., Takeuchi, I., Eds.; Frontiers Science
Series No. 21; Universal Academy Press, Inc.: Tokyo, 1997.
(2) (a) Morris, H. R.; Taylor, G. W.; Masento, M. S.; J ermyn, K. A.;
Kay, R. R. Nature 1987, 328, 811-814. (b) Morris, H. R.; Masento, M.
S.; Taylor, G. W.; J ermyn, K. A.; Kay, R. R. Biochem. J . 1988, 249,
903-906.
(3) Abe, H.; Uchiyama, M.; Tanaka, Y.; Saito, H. Tetrahedron Lett.
1976, 42, 3807-3810.
(4) Asahi, K.; Sakurai, A.; Takahashi, N.; Kubohara, Y.; Okamoto,
K.; Tanaka, Y. Biochem. Biophys. Res. Commun. 1995, 208, 1036-
1039.
(6) Sawada, T.; Aono, M.; Asakawa, S.; Ito, A.; Awano, K. J . Antibiot.
(Tokyo) 2000, 53, 959-966.
(7) Takaya, Y.; Kikuchi, H.; Terui, Y.; Komiya, J .; Furukawa, K.;
Seya, K.; Motomura, S.; Ito, A.; Oshima, Y. J . Org. Chem. 2000, 65,
985-989.
(5) Miwa, Y.; Sasaguri, T.; Kosaka, C.; Taba, Y.; Ishida, A.; Abumiya,
T.; Kubohara, Y. Circ. Res. 2000, 86, 68-75.
(8) Takaya, Y.; Kikuchi, H.; Terui, Y.; Komiya, J .; Maeda, Y.; Ito,
A.; Oshima, Y. Tetrahedron Lett. 2001, 42, 61-63.
10.1021/jo015657x CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/21/2001

Furanodictine A and B: Amino Sugar Analogues
J . Org. Chem., Vol. 66, No. 21, 2001 6983
Ta ble 1. 13C a n d 1H NMR Sp ectr a l Da ta of F u r a n od ictin e A (1)
a
Multiplicity was obscure because of overlap with the signal of H-4 in R-anomer. b,c These signals were not distinguishable.
Ta ble 2. 13C a n d 1H NMR Sp ectr a l Da ta of F u r a n od ictin e B (2)
R-anomer (2a )
â-anomer (2b)
positions
13C
1H
13C
1H
1
2
3
4
5
6
103.8
59.3
80.4
79.9
73.0
70.8
5.22 (1H, br.s)
96.7
54.8
81.0
81.0
73.6
70.3
5.36 (1H, dd, J ) 6.8, 5.3 Hz)
4.43 (1H, dt, J ) 8.4, 5.3 Hz)
4.51 (1H, dd, J ) 5.3, 4.8 Hz)
4.82 (1H, dd, J ) 5.4, 4.8 Hz)
5.10 (1H, td, J ) 6.2, 5.4 Hz)
4.08 (1H, dd, J ) 9.5, 6.2 Hz)
3.95 (1H, dd, J ) 9.5, 6.2 Hz)
4.20 (1H, td, J ) 6.3, 4.2 Hz)
4.59 (1H, dd, J ) 6.3, 5.0 Hz)
4.97 (1H, t, J ) 5.0 Hz)
5.15 (1H, td, J ) 6.0, 5.0 Hz)
4.05 (1H, dd, J ) 9.5, 6.0 Hz)
3.80 (1H, dd, J ) 9.5, 6.0 Hz)
1′
2′
172.2
43.1
172.3
43.0
2.26 (1H, dd, J ) 15.0, 7.3 Hz)
2.22 (1H, dd, J ) 15.0, 7.0 Hz)
2.08-2.15 (1H, m)
0.95 (3H, d, J ) 6.6 Hz)
0.95 (3H, d, J ) 6.6 Hz)
2.28 (1H, dd, J ) 15.0, 7.3 Hz)
2.24 (1H, dd, J ) 15.0, 7.0 Hz)
2.08-2.15 (1H, m)
0.96 (3H, d, J ) 6.6 Hz)
0.96 (3H, d, J ) 6.6 Hz)
3′
4′
5′
1′′
25.7
22.5a
22.4a
171.0
23.2
25.6
22.5b
22.4b
170.2
23.2
2′′
2.03 (3H, s)
2.04 (3H, s)
1-OH
2-NH
3.80-3.82 (1H, br.s)
6.15 (1H, d, J ) 6.3 Hz)
3.31 (1H, d, J ) 6.8 Hz)
6.12 (1H, d, J ) 8.4 Hz)
a,b
These signals were not distinguishable.
The H and 13C NMR spectra of 1 suggested that 1 is
an equilibrium mixture of two stereoisomers (1a and 1b)
in a ratio of 7:1. The molecular formula C13H21NO6
indicated for 1 was established by HREI-MS (m/z 288.1429
[M + H]+) and 1H and 13C NMR spectra (Table 1). We
first analyzed NMR signals assignable to the major
isomer (1a ). The 13C NMR spectrum of 1a revealed the
presence of two carbonyls, an acetal, three oxymethines,
an oxymethylene, a nitrogen-adjacent methine, a me-
thine, a methylene, and three methyls. 1H NMR spectrum
of 1a exhibited signals due to the protons of an acetal (δ
5.56 (1H, dd, J ) 4.7, 3.7 Hz)), three oxymethines (δ 5.00
(1H, ddd, J ) 7.4, 6.3, 5.4 Hz), 4.91 (1H, t, J ) 5.4 Hz),
and 4.58 (1H, dd, J ) 5.4, 4.0 Hz)), an oxymethylene (δ
4.07 (1H, dd, J ) 9.4, 6.3 Hz) and 3.82 (1H, dd, J ) 9.4,
7.4 Hz)), and a nitrogen-adjacent methine (δ 4.38-4.45
(1H, m)). 1H-1H COSY unambiguously gave the sequence
of the protons suggesting that 1a is an analogue of an
amino sugar. 1H-1H COSY also pointed out the presence
of an isovaleryloxy group. In the heteronuclear multiple-
bond correlation (HMBC) spectrum, two carbonyl carbons
(δ 170.6 and 172.6) were correlated through three σ-bonds
with the nitrogen-adjacent methine (δ 4.41) and oxyme-
thine (δ 5.00) protons, respectively, while the long-range
C-H correlations indicated the presence of the acetamide
and isovaleryloxy groups at C-2 and C-5 (Figure 1). The
3,6-anhydrohexofuranose carbon skeleton of 1a was
1
F igu r e 1. Planar structure of R-anomer of furanodictine A
(1a ).
F igu r e 2. Relative structure of R-anomer of furanodictine A
(1a ).
deduced by long-range C-H couplings of C-3-H-6, C-6-
H-3, and C-4-H-1 (Figure 1). NOESY spectrum exhibited
cross peaks as follows: H-1-H-2, H-3-H-4, and H-4-
H-5 (Figure 2), indicating that the acetal, nitrogen-
adjacent methine, and oxymethine protons at C-1 to C-5
are situated spatially as â, â, R, R, and R, respectively.
The relative stereostructure of 1a is, therefore, repre-
sented as shown in the formula, which is thought to be
biotransformed from N-acetylglucosamine (Figure 2). 1b
1
was deduced to be a â-anomer using a H-1H COSY and
NOESY spectrum.

6984 J . Org. Chem., Vol. 66, No. 21, 2001
Kikuchi et al.
Sch em e 1a
a
Reagents and conditions: (i) MeOH, cat. H2SO4, reflux; (ii) Ac2O, pyridine, rt; (iii) NaOMe, MeOH, rt; (iv) p-TsCl, pyridine, 0 °C; (v)
NaOMe, MeOH, reflux; (vi) allyl alcohol, cat. H2SO4, reflux; (vii) Ac2O, pyridine, rt; (viii) NaOMe, MeOH, rt; (ix) isovaleric acid, EDCI,
DMAP, CH2Cl2, rt; (x) Wilkinson’s catalyst, DABCO, EtOH-H2O (9:1), reflux; (xi) microencapsulated OsO4, NMO, H2O-acetonitrile-
acetone (1:1:1), rt
The HREI-MS of 2 gave the same molecular formula,
C13H21NO6, as that of 1. As in the case of 1, 2 is composed
of two stereoisomers (2a and 2b), which equilibrate in a
ratio of 2:3. Both the stereoisomers (2a and 2b) showed
similar correlations of H-2-H-3, H-3-H-4, and H-4-H-5
in the NOESY spectrum, indicating that H-2 to H-5 are
2 was synthesized from an anomeric mixture of N-
oriented in the same plane. The observation of NOE
acetyl-D-mannosamine (10) in a similar manner as 1, but
between H-1 and H-2 only in 2b helped to determine that
the R- and â-anomers of allyl glycoside (14a and 14b)
could not be separated by silica gel chromatography.
All of the spectral data on synthetic furanodictine A
and B, including their respective specific rotations, were
2a and 2b are R- and â-anomers, respectively, and that
they might be derived from N-acetylmannosamine.
Syn th esis a n d Absolu te Con figu r a tion . To deter-
mine the absolute configurations of 1 and 2, total
identical with those of their respective natural com-
syntheses of these compounds were carried out (Scheme
pounds. From this result, the absolute configurations of
1).
1 and 2 were determined to be 2R, 3R, 4S, 5R and 2S,
The anomeric mixture of N-acetyl-D-glucosamine (3)
3R, 4S, 5R, which are the same as those of N-acetyl-D-
was used as a starting material in the synthesis of 1.
glucosamine (3) and N-acetyl-D-mannosamine (10), re-
spectively.
Biologica l E va lu a t ion .PC-12 cells were used to
evaluate the potency of the effects of the compounds on
neuronal differentiation. These cells were cultivated in
Dulbecco’s modified Eagle’s medium (DMEM) containing
0.5% FCS with 1 or 2 at the concentrations of 0.5-50
The treatment of 3 in 5% sulfuric acid-methanol gave a
mixture of R- and â-anomers of the methyl glycoside and
their deacetylated products. Acetylation of the mixture
of the compounds with acetic anhydride-pyridine af-
forded R- and â-anomers (4a and 4b) of the tetraacety-
lated compound. Deacetylation of the R-anomer (4a ),
using sodium methoxide, and subsequent tosylation, with
µΜ for 4 days. This was followed by the observation of
p-tosyl chloride in pyridine, gave 6-O-tosylate (5a ). 3,6-
neurite outgrowth of the cells under a phase-contrast
Anhydroglucofuranoside (6a ) prepared from 5a with
microscope. 2 caused the PC-12 cells to change in
sodium methoxide was refluxed in 5% sulfuric acid-allyl
morphology and extend neurites in a concentration-
alcohol to obtain the mixture of 3,6-anhydroglucofura-
dependent manner with an EC50 value of about 2 µM.
The number of cells bearing neurites increased from 10
to 18% upon the addition of 2 at a concentration of 20
noside and its deacetylated product. Acetylation of this
mixture gave R- and â-anomers (7a and 7b) of the allyl
glycoside. 4b was also converted into 7a and 7b by the
µM. Despite the apparent activity of 2, 1 only weakly
same sequential treatment as the R-anomer (4a). Deacety-
induced the morphological differentiation. However, both
lation of the R-anomer (7a ), using sodium methoxide, and
subsequent esterification, with isovaleric acid in the
1 and 2 at concentrations of 0.5-5 µΜ caused a great
extent of neurite extension in the presence of 2 ng mL-1
presence of EDCI and DMAP, gave an isovalerate (8a ).
9
of nerve growth factor (NGF). These results indicate that
furanodictines have the ability to cause neuronal dif-
ferentiation.
Deallylation of 8a using PdCl2 did not give 1 but
oxazoline (9) as a major product. The treatment of 8a
with Wilkinson’s catalyst in 10% aqueous ethanol fol-
lowed by oxidative cleavage of 1-propenyl glycoside with
microencapsulated osmium tetroxide10,11 allowed us to
complete the synthesis of 1. The â-anomer (7b) was also
converted into 1 by the similar sequential treatment as
the R-anomer (7a ).
Con clu sion
To the best of our knowledge, 1 and 2 are the first
examples of amino sugar analogues that bear a 3,6-
anhydrohexofuranose carbon skeleton and are derived
from natural sources. Their isolation may draw attention
as amino sugars rarely occur as free compounds or as
simple derivatives. The Streptomyces family of molds is
a particularly abundant source of a variety of amino
sugars, thus becoming the popular source of various
(9) Ogawa, T.; Kitajima, T.; Nukada, T. Carbohydr. Res. 1983, 123,
C5-C7.
(10) Lamberth, C.; Bernarski, M. D. Tetrahedron Lett. 1991, 32,
7369-7372.
(11) Nagayama, S.; Endo, M.; Kobayashi, S. J . Org. Chem. 1998,
63, 6094-6095.

Furanodictine A and B: Amino Sugar Analogues
J . Org. Chem., Vol. 66, No. 21, 2001 6985
antibiotics containing amino sugars.12 The isolation of
R-pyrones and aromatic compounds from Dictyostelium
cellular slime molds previously described7,8 implies that
cellular slime molds may have a diversity of secondary
metabolites as the Streptomyces family. Furthermore, our
study demonstrating that 2, derived from N-acetylman-
nosamine ocurring in glycoproteins but to rather limited
extent compared to N-acetylglucosamine,12 shows a strong
neuronal differentiation activity suggests that the activ-
ity can be a focus in the biological study of the functions
of amino sugars.
J ) 12.4, 4.7 Hz), 4.07 (1H, dd, J ) 12.4, 2.4 Hz), 3.88 (1H,
ddd, J ) 10.1, 4.7, 2.4 Hz), 3.37 (3H, s), 2.06 (3H, s), 1.99 (3H,
s), 1.98 (3H, s), 1.92 (3H, s); 13C NMR (CDCl3, 125 MHz) δ
171.3, 170.6, 169.8, 169.2, 98.3, 71.3, 68.1, 67.6, 62.0, 55.4, 51.8,
23.1, 20.7 (2C), 20.5; EI-MS m/z 362 [M + H]+, 330, 302, 43
(base); HREI-MS m/z 362.1454 (362.1452 calcd for C15H24NO9).
1
4b: a colorless oil; H NMR (CDCl3, 500 MHz) δ 5.68 (1H, d,
J ) 8.8 Hz), 5.28 (1H, dd, J ) 10.5, 9.6 Hz), 5.08 (1H, t, J )
9.6 Hz), 4.60 (1H, d, J ) 8.3 Hz), 4.28 (1H, dd, J ) 12.3, 4.8
Hz), 4.15 (1H, dd, J ) 12.3, 2.4), 3.88 (1H, dt, J ) 10.5, 8.6
Hz), 3.72 (1H, ddd, J ) 10.0, 4.8, 2.4 Hz), 3.50 (3H, s), 2.09
(3H, s), 2.03 (3H, s), 2.03 (3H, s), 1.96 (3H, s); 13C NMR (CDCl3,
125 MHz) δ 170.9, 170.7, 170.2, 169.3, 101.6, 72.4, 71.8, 68.7,
62.1, 56.7, 54.6, 23.3, 20.7, 20.6, 20.6; EI-MS m/z 362 [M +
H]+,346, 330, 302, 288, 43 (base); HREI-MS m/z 362.1477
(362.1452 calcd for C15H24NO9).
Exp er im en ta l Section
Gen er a l Meth od s. Analytical TLC was performed on silica
gel 60 F254 (Merck). Column chromatography was carried out
on silica gel 60 (70-230 mesh, Merck). Chemical shifts for 1H
and 13C NMR are given in parts per million (δ) relative to
internal standards.
Or ga n ism a n d Cu ltu r e Con d ition s. Cellular slime mold,
D. discoideum NC-4, was kindly supplied by Professor Y.
Maeda, Tohoku University. Spores were cultured at 22 °C with
Escherichia coli Br on A-medium consisting of 0.5% glucose,
0.5% polypeptone, 0.05% yeast extract, 0.225% KH2PO4,
0.137% Na2HPO4‚12H2O, 0.05% MgSO4‚7H2O, and 1.5% agar.
When the fruit body was formed in 5 days, they were harvested
for extraction.
Meth yl 2-a ceta m id o-2-d eoxy-6-O-tosyl-r-D-glu cop yr a -
n osid e (5a ). 4a (2.97 g, 8.23 mmol) in methanol (40 mL) was
treated with sodium methoxide (2.00 g, 37.0 mmol) at room
temperature for 3 h. The mixture was neutralized with Dowex
50w (H+) until the pH reached 3. The solvent was evaporated
to give a white solid which was methyl 2-acetamido-2-deoxy-
R-D-mannopyranoside. This solid was dissolved in pyridine (20
mL), and this solution was cooled to 0 °C. p-Toluenesulfonyl
chloride (1.73 g, 0.905 mmol) was added to the solution. After
3 h, the reaction was quenched by the use of methanol (10
mL). The mixture was poured into 0.1 M hydrochloric acid (100
mL) and extracted three times with ethyl acetate. The organic
layer was washed with saturated sodium bicarbonate solution,
water, and brine, dried over anhydrous sodium sulfate, and
evaporated. The residue was purified by SiO2 column chro-
matography (chloroform-methanol, 96:4) to give 5a (1.22 g,
38%). 5a : colorless needles; 1H NMR (CD3OD, 500 MHz) δ
7.79 (2H, d, J ) 8.2 Hz), 7.43 (2H, d, J ) 8.2 Hz), 4.52 (1H, d,
J ) 3.6 Hz), 4.32 (1H, dd, J ) 10.8, 1.8 Hz), 4.18 (1H, dd, J )
10.8, 6.0 Hz), 3.81 (1H, dd, J ) 10.7, 3.6 Hz), 3.65 (1H, ddd, J
) 10.0, 6.0, 1.8 Hz), 3.55 (1H, dd, J ) 10.7, 8.8 Hz), 3.28 (3H,
s), 3.24 (1H, dd, J ) 10.0, 8.8 Hz), 2.44 (3H, s), 1.95 (3H, s);
13C NMR (CD3OD, 125 MHz) δ 173.4, 146.5, 134.5, 131.0 (2C),
129.1 (2C), 99.7, 72.8, 71.9, 71.1, 71.0, 55.6, 55.1, 22.5, 21.6;
EI-MS m/z 389 [M]+, 357, 60 (base), 43; HREI-MS m/z
389.1112 (389.1149 calcd for C16H23NO8S).
Isola tion of 1 a n d 2. The cultured fruit body (wet wt 109
g) of D. discoideum was extracted twice with methanol at room
temperature to give the extract (5.6 g). This extract was
partitioned with ethyl acetate and water to yield ethyl acetate
solubles (1.1 g). The ethyl acetate solubles were chromato-
graphed over SiO2, and the column was eluted with n-hex-
anes-ethyl acetate mixtures with increasing polarity. Ethyl
acetate eluent (130 mg) was further chromatographed over
ODS using a methanol-water mixture to give crude furano-
dictines. The crude sample was purified by SiO2 column
chromatography (chloroform-methanol, 27:1) to give 1 (1.9
mg) and 2 (2.8 mg). 1: [R]25 +100.4 (c 0.233, CHCl3); a
D
colorless oil; H NMR and 13C NMR data are shown in Table
1
1; EI-MS m/z 288 [M + H]+, 270, 258, 244, 227, 60 (base), 43;
HREI-MS m/z 288.1429 (288.1446 calcd for C13H22NO6). 2:
Meth yl 2-a ceta m id o-2-d eoxy-6-O-tosyl-â-D-glu cop yr a -
n osid e (5b). By the use of 4b (1.87 g, 5.18 mmol) as a
substrate, 5b (746 mg, 37%) was afforded in the same manner
[R]25 +85.6 (c 0.250, CHCl3); a colorless oil; 1H NMR and 13C
D
NMR data are shown in Table 2; EI-MS m/z 288 [M + H]+,
270, 258, 244, 227, 60 (base), 43; HREI-MS m/z 288.1455
(288.1446 calcd for C13H22NO6).
1
as the synthesis of 5a . 5b: colorless needles; H NMR (CD3-
OD, 500 MHz) δ 7.79 (2H, d, J ) 8.4 Hz), 7.43 (2H, d, J ) 8.4
Hz), 4.34 (1H, dd, J ) 10.8, 2.0 Hz), 4.24 (1H, d, J ) 8.5 Hz),
4.16 (1H, dd, J ) 10.8, 6.0 Hz), 3.55 (1H, dd, J ) 10.3, 8.5
Hz), 3.35-3.42 (2H, m), 3.34 (3H, s), 3.22 (1H, dd, J ) 9.8, 8.9
Hz), 2.44 (3H, s), 1.94 (3H, s); 13C NMR (CD3OD, 125 MHz) δ
173.8, 146.5, 134.4, 131.0 (2C), 129.1 (2C), 103.3, 75.9, 75.0,
71.6, 70.8, 57.1, 56.9, 22.9, 21.6; EI-MS m/z 389 [M]+, 357, 43
Meth yl 2-a ceta m id o-3,4,6-O-tr ia cetyl-2-d eoxy-r-D-glu -
cop yr a n osid e (4a ) a n d m eth yl 2-a ceta m id o-3,4,6-O-tr i-
a cetyl-2-d eoxy-â-D-glu cop yr a n osid e (4b). N-Acetyl-D-glu-
cosamine (2-acetamido-2-deoxy-D-glucopyranose) (3) (5.00 g,
22.6 mmol) was dissolved in methanol (40 mL), and sulfuric
acid (0.8 mL) was added to this solution. After being refluxed
for 3 h, the mixture was neutralized with Dowex 1 × 8 (OH-)
until the pH reached 10. The solvent was evaporated to give
a residue which was the mixture of methyl 2-acetamido-2-
deoxy-D-glucopyranoside and methyl 2-amino-2-deoxy-D-glu-
copyranoside. This mixture was treated with an excess of acetic
anhydride (10 mL) in pyridine (25 mL). After 10 h, the mixture
was poured into 0.1 M hydrochloric acid (100 mL) and
extracted three times with ethyl acetate. The organic layer
was washed with saturated sodium bicarbonate solution,
water, and brine, dried over anhydrous sodium sulfate, and
evaporated. The residue was purified by SiO2 column chro-
matography to give 4a (3.08 g, 38%), which was eluted by
chloroform, and 4b (1.98 g, 24%), which was eluted by
chloroform-methanol (99:1). 4a : a colorless oil; 1H NMR
(CDCl3, 500 MHz) δ 5.67 (1H, d, J ) 9.5 Hz), 5.17 (1H, dd, J
) 10.5, 9.6 Hz), 5.08 (1H, dd, J ) 10.1, 9.6 Hz), 4.69 (1H, d, J
) 3.7 Hz), 4.31 (1H, ddd, J ) 10.6, 9.6, 3.7 Hz), 4.20 (1H, dd,
(base); HREI-MS m/z 389.1178 (389.1149 calcd for C16H23
-
NO8S).
Met h yl 2-a cet a m id o-3,6-a n h yd r o-2-d eoxy-r-D-glu co-
fu r a n osid e (6a ). 5a (1.20 g, 3.08 mmol) in methanol (30 mL)
was treated with sodium methoxide (500 mg, 9.26 mmol) and
stirred for 3 h at 65 °C. After being cooled, the mixture was
acidified with Dowex 50w (H+) until the pH reached 3. The
solvent was evaporated, and the residue was purified by SiO2
column chromatography (chloroform-methanol 96:4) to give
6a (494 mg, 79%). 6a : colorless and amorphous; 1H NMR
(CDCl3, 500 MHz) δ 6.00 (1H, br.s), 5.09 (1H, d, J ) 4.3 Hz),
4.55 (1H, t, J ) 5.4 Hz), 4.44-4.48 (2H, m), 4.18-4.23 (1H,
m), 3.97 (1H, dd, J ) 9.4, 6.0 Hz), 3.62 (1H, dd, J ) 9.4, 7.5
Hz), 3.42 (3H, s), 2.51 (1H, d, J ) 8.5 Hz), 2.02 (3H, s); 13C
NMR (CDCl3, 125 MHz) δ 169.8, 104.2, 87.1, 78.8, 71.5, 71.0,
58.4, 55.3, 23.2; EI-MS m/z 218 [M + H]+, 185, 158, 128, 43
(base); HREI-MS m/z 218.1036 (218.1027 calcd for C9H16NO5).
Met h yl 2-a cet a m id o-3,6-a n h yd r o-2-d eoxy-â-D-glu co-
fu r a n osid e (6b). By the use of 5b (741 mg, 1.90 mmol) as a
substrate, the reaction was carried out in the same manner
as the synthesis of 6a . The crude product was purified by SiO2
column chromatography to give 6a (24 mg, 6%), which was
(12) Comprehensive Organic Chemistry The Synthesis and Reactions
of Organic Compounds; Haslam, E., Ed.; Pergamon Press: Oxford,
1979; Vol. 5.

6986 J . Org. Chem., Vol. 66, No. 21, 2001
Kikuchi et al.
eluted by chloroform-methanol (96:4), and 6b (329 mg, 86%),
which was eluted by chloroform-methanol (90:10). 6b: color-
(1H, dd, J ) 9.3, 7.8 Hz), 2.28 (1H, dd, J ) 14.7, 7.5 Hz), 2.24
(1H, dd, J ) 14.7, 6.8 Hz), 2.08-2.16 (1H, m), 2.02 (3H, s),
0.98 (6H, d, J ) 6.6 Hz); 13C NMR (CDCl3, 125 MHz) δ 172.4,
169.8, 133.5, 117.8, 102.3, 87.4, 77.7, 72.0, 68.5, 68.3, 58.2, 43.0,
25.7, 23.2, 22.2, 22.2; EI-MS m/z 328 [M + H]+, 286, 268, 202,
85 (base), 57, 43; HREI-MS m/z 328.1805 (328.1759 calcd for
1
less and amorphous; H NMR (CDCl3, 500 MHz) δ 5.80 (1H,
br.s), 4.99 (1H, s), 4.83 (1H, t, J ) 5.7 Hz), 4.40 (1H, d, J )
5.5 Hz), 4.31 (1H, d, J ) 7.4 Hz), 4.22 (1H, dq, J ) 10.2, 5.7
Hz), 3.82 (2H, d, J ) 5.7 Hz), 3.49 (3H, s), 2.86 (1H, d, J )
10.2 Hz), 2.01 (3H, s); 13C NMR (CDCl3, 125 MHz) δ 169.7,
110.8, 86.3, 84.1, 73.7, 71.2, 61.7, 56.4, 23.1; EI-MS m/z 218
[M + H]+, 185, 158, 128, 43 (base); HREI-MS m/z 218.1024
(218.1027 calcd for C9H16NO5).
C
16H26NO6).
Allyl 2-a ceta m id o-3,6-a n h yd r o-2-d eoxy-5-O-isova ler yl-
â-D-glu cofu r a n osid e (8b). By the use of 7b (299 mg, 1.05
mmol) as a substrate, 8b (264 mg, 77%) was afforded in the
1
Allyl 2-a ceta m id o-5-O-a cetyl-3,6-a n h yd r o-2-d eoxy-r-D-
glu cofu r a n osid e (7a ) a n d a llyl 2-a ceta m id o-5-O-a cetyl-
3,6-a n h yd r o-2-d eoxy-â-D-glu cofu r a n osid e (7b). Sulfuric
acid (0.3 mL) was added to a solution of 6a (478 mg, 2.19
mmol) in allyl alcohol (10 mL). After being stirred at 80 °C for
2 h, the mixture was neutralized with Dowex 1 × 8 (OH-) until
the pH reached 10. The solvent was evaporated to give a
residue which was the mixture of allyl 2-acetamido-3,6-
anhydro-2-deoxy-D-glucofuranoside and allyl 2-amino-3,6-an-
hydro-2-deoxy-D-glucofuranoside. This mixture was treated
with an excess of acetic anhydride (1.3 mL) in pyridine (10
mL). After 10 h, the mixture was poured into 0.1 M hydro-
chloric acid (40 mL) and extracted three times with ethyl
acetate. The organic layer was washed with saturated sodium
bicarbonate solution, water, and brine, dried over anhydrous
sodium sulfate, and evaporated. The residue was purified by
SiO2 column chromatography to give 7a (337 mg, 54%), which
was eluted by chloroform-methanol (99:1), and 7b (190 mg,
30%), which was eluted by chloroform-methanol (95:5).
By the use of 6b (320 mg, 1.47 mmol) as a substrate, 7a
(202 mg, 48%) and 7b (122 mg, 29%) were afforded in the same
manner described above. 7a : a colorless oil; 1H NMR (CDCl3,
500 MHz) δ 6.05 (1H, d, J ) 7.5 Hz), 5.87 (1H, dddd, J ) 17.2,
10.4, 6.1, 5.3 Hz), 5.26 (1H, dq, J ) 17.2, 1.5 Hz), 5.20-5.22
(1H, m), 5.20 (1H, d, J ) 4.3 Hz), 4.99 (1H, dt, J ) 7.5, 6.0
Hz), 4.75 (1H, t, J ) 5.3 Hz), 4.47-4.52 (2H, m), 4.22 (1H,
ddt, J ) 12.8, 5.3, 1.5 Hz), 4.06 (1H, dd, J ) 9.3, 6.3 Hz), 4.01
(1H, ddt, J ) 12.8, 6.1, 1.2 Hz), 3.82 (1H, dd, J ) 9.3, 7.8 Hz),
2.13 (3H, s), 2.02 (3H, s); 13C NMR (CDCl3, 125 MHz) δ 170.3,
169.8, 133.6, 117.7, 102.5, 87.3, 77.7, 72.2, 68.5, 68.2, 58.2, 23.1,
20.6; EI-MS m/z 286 [M + H]+, 244, 226, 202, 43 (base); HREI-
same manner as the synthesis of 8a . 8b: a colorless oil; H
NMR (CDCl3, 500 MHz) δ 5.85-5.96 (2H, m), 5.30 (1H, dq, J
) 17.2, 1.7 Hz), 5.20 (1H, dq, J ) 10.4, 1.5 Hz), 5.03 (1H, s),
4.93-4.98 (2H, m), 4.53 (1H, d, J ) 4.7 Hz), 4.38 (1H, d, J )
7.6 Hz), 4.26 (1H, ddt, J ) 12.8, 5.2, 1.5 Hz), 3.96-4.08 (3H,
m), 2.25-2.27 (2H, m), 2.09-2.17 (1H, m), 1.99 (3H, s), 0.99
(6H, d, J ) 6.6 Hz); 13C NMR (CDCl3, 125 MHz) δ 172.5, 169.6,
133.6, 117.4, 107.5, 86.5, 81.1, 73.1, 68.6, 68.5, 62.3, 43.1, 25.7,
23.1, 22.4, 22.3; EI-MS m/z 328 [M + H]+, 286, 268, 253, 85
(base), 57, 43; HREI-MS m/z 328.1780 (328.1759 calcd for
C
16H26NO6).
2-Aceta m ido-3,6-a n h ydr o-2-deoxy-5-O-isova ler yl-D-glu -
cofu r a n ose (fu r a n od ictin e A) (1). Chlorotris(triphenylphos-
phine)rhodium(I) (157 mg, 0.170 mmol) and DABCO (19.1 mg,
0.170 mmol) were added to a solution of 8a (278 mg, 0.849
mmol) in ethanol-water (9:1) (7 mL). After being refluxed for
2 h, the mixture was filtered with ethyl acetate, and the filtrate
was evaporated. The residue was purified by SiO2 column
chromatography (ethyl acetate-methanol, 39:1) to give 1-pro-
penyl glycoside. This glycoside was dissolved in water-
acetonitrile-acetone (1:1:1) (7 mL). N-Methylmorpholine N-
oxide (129 mg, 1.10 mmol) and microencapsulated osmium
tetroxide (110 mg, it contains 10% osmium tetroxide; Wako
Pure Chemicals, Osaka) were added to this solution. After
being stirred at room temperature for 9 h, the mixture was
filtered with methanol, and the filtrate was evaporated. The
residue was purified by SiO2 column chromatography (ethyl
acetate-methanol, 9:1) to give 1 (137 mg, 56% from 8a ). By
the use of 8b (140 mg, 0.426 mmol) as a substrate, 1 (85.1
mg, 69% from 8b) was afforded in the same manner as
described above.Synthetic 1: [R]25 +118.5 (c 0.437, CHCl3);
D
MS m/z 286.1268 (286.1289 calcd for C13H20NO6). 7b:
a
other spectral data were identical with those of the natural
product.
colorless oil; 1H NMR (CDCl3, 500 MHz) δ 6.06 (1H, br.s), 5.92
(1H, dddd, J ) 17.2, 10.4, 6.0, 5.2 Hz), 5.30 (1H, dq, J ) 17.2,
1.7 Hz), 5.20 (1H, dq, J ) 10.4, 1.5 Hz), 5.03 (1H, s), 4.93-
4.97 (2H, m), 4.53 (1H, d, J ) 4.6 Hz), 4.37 (1H, d, J ) 7.5
Hz), 4.26 (1H, ddt, J ) 12.7, 5.2, 1.5 Hz), 3.98-4.07 (3H, m),
2.13 (3H, s), 1.99 (3H, s); 13C NMR (CDCl3, 125 MHz) δ 170.3,
169.7, 133.5, 117.4, 107.6, 86.6, 81.1, 73.2, 68.6, 68.6, 62.3, 23.0,
20.6; EI-MS m/z 286 [M + H]+, 244, 226, 202, 43 (base); HREI-
MS m/z 286.1329 (286.1289 calcd for C13H20NO6).
Allyl 2-a ceta m id o-3,6-a n h yd r o-2-d eoxy-5-O-isova ler yl-
r-D-glu cofu r a n osid e (8a ). 7a (517 mg, 1.81 mmol) in metha-
nol (10 mL) was treated with sodium methoxide (120 mg, 2.22
mmol) at room temperature for 2 h. The mixture was neutral-
ized with Dowex 50w (H+) until the pH reached 3. The solvent
was evaporated to give a white solid which was allyl 2-aceta-
mido-3,6-anhydro-2-deoxy-R-D-glucofuranoside. This solid was
dissolved in dichloromethane (10 mL), and the solution was
cooled at 0 °C. Isovaleric acid (240 µL, 2.20 mmol), 1-ethyl-3-
(3-dimethylaminopropyl)carbodiimide hydrochloride (694 mg,
3.62 mmol), and DMAP (221 mg, 1.81 mmol) were added to
this solution. After being stirred for 3 h, the mixture was
poured into 0.1 M hydrochloric acid (40 mL) and extracted
three times with ethyl acetate. The organic layer was washed
with saturated sodium bicarbonate solution, water, and brine,
dried over anhydrous sodium sulfate, and evaporated. The
residue was purified by SiO2 column chromatography (chlo-
Meth yl 2-a ceta m id o-3,4,6-O-tr ia cetyl-2-d eoxy-r-D-m a n -
n op yr a n osid e (11a ) a n d m eth yl 2-a ceta m id o-3,4,6-O-
tr ia cetyl-2-d eoxy-â-D-m a n n op yr a n osid e (11b). By the use
of N-acetyl-D-mannosamine (2-acetamido-2-deoxy-D-mannopy-
ranose) monohydrate (10) (233 mg, 0.974 mmol) as a substrate,
the reaction was carried out in the same manner as the
synthesis of 4a and 4b. The crude product was purified by SiO2
column chromatography to give 11a (197 mg, 56%), which was
eluted by chloroform, and 11b (118 mg, 34%), which was eluted
by chloroform-methanol (99:1). 11a : a colorless oil; 1H NMR
(CDCl3, 500 MHz) δ 6.00 (1H, d, J ) 9.1 Hz), 5.32 (1H, dd, J
) 10.2, 4.5 Hz), 5.10 (1H, t, J ) 10.2 Hz), 4.66 (1H, d, J ) 1.4
Hz), 4.62 (1H, ddd, J ) 9.1, 4.5, 1.4 Hz), 4.28 (1H, dd, J )
12.2, 5.8 Hz), 4.08 (1H, dd, J ) 12.2, 2.4 Hz), 3.97 (1H, ddd, J
) 10.2, 5.8, 2.4 Hz), 3.40 (3H, s), 2.11 (3H, s), 2.05 (3H, s),
2.05 (3H, s), 1.99 (3H, s); 13C NMR (CDCl3, 125 MHz) δ 170.5,
170.0, 169.8, 169.8, 100.0, 69.0, 67.8, 66.1, 62.5, 55.1, 50.1, 23.1,
20.6 (2C), 20.5; EI-MS m/z 362 [M + H]+, 346, 330, 302, 43
(base); HREI-MS m/z 362.1451 (362.1452 calcd for C15H24NO9).
11b: a colorless oil; 1H NMR (CDCl3, 500 MHz) δ 6.15 (1H, d,
J ) 8.8 Hz), 5.57 (1H, dd, J ) 5.5, 3.5 Hz), 5.19 (1H, ddd, J )
9.5, 5.5, 2.4 Hz), 4.88 (1H, d, J ) 4.1 Hz), 4.69 (1H, ddd, J )
8.8, 5.5, 4.1 Hz), 4.53 (1H, dd, J ) 12.2, 2.4 Hz), 4.34 (1H, dd,
J ) 9.5, 3.5 Hz), 4.14 (1H, dd, J ) 12.2, 5.5 Hz), 3.38 (3H, s),
2.08 (3H, s), 2.07 (3H, s), 2.01 (3H, s), 1.99 (3H, s); 13C NMR
(CDCl3, 125 MHz) δ 170.6, 169.8, 169.7, 169.2, 107.6, 76.4,
71.5, 67.7, 63.0, 56.9, 55.7, 22.9, 20.7, 20.6, 20.4; EI-MS m/z
362 [M + H]+, 330, 302, 288, 43 (base); HREI-MS m/z 362.1459
(362.1452 calcd for C15H24NO9).
roform-methanol, 99:1) to give 8a (399 mg, 67%). 8a :
a
colorless oil; 1H NMR (CDCl3, 500 MHz) δ 6.05 (1H, d, J ) 7.6
Hz), 5.87 (1H, dddd, J ) 17.2, 10.4, 6.0, 5.3 Hz), 5.25 (1H, dq,
J ) 17.2, 1.4 Hz), 5.18-5.22 (1H, m), 5.18 (1H, d, J ) 4.6 Hz),
4.99 (1H, dt, J ) 7.5, 6.0 Hz), 4.77 (1H, t, J ) 5.3 Hz), 4.47-
4.52 (2H, m), 4.20(1H, ddt, J ) 12.8, 5.3, 1.5 Hz), 4.06 (1H,
dd, J ) 9.3, 6.3 Hz), 4.00 (1H, ddt, J ) 12.8, 6.3, 1.2 Hz), 3.83
Meth yl 2-a ceta m id o-2-d eoxy-6-O-tosyl-r-D-m a n n op y-
r a n osid e (12a ). By the use of 11a (101.1 mg, 0.280 mmol) as
a substrate, 12a (60.1 mg, 55%) was afforded in the same

Furanodictine A and B: Amino Sugar Analogues
J . Org. Chem., Vol. 66, No. 21, 2001 6987
manner as the synthesis of 5a . 12a : colorless needles; 1H NMR
(CD3OD, 500 MHz) δ 7.80 (2H, d, J ) 8.2 Hz), 7.43 (2H, d, J
) 8.2 Hz), 4.48 (1H, d, J ) 1.4 Hz), 4.36 (1H, dd, J ) 10.7, 1.9
Hz), 4.21 (1H, dd, J ) 5.2, 1.4 Hz), 4.20 (1H, dd, J ) 10.7, 7.0
Hz), 3.84 (1H, dd, J ) 9.6, 5.2 Hz), 3.64 (1H, ddd, J ) 9.9, 7.0,
1.9 Hz), 3.45 (1H, t, J ) 9.8 Hz), 3.27 (3H, s), 2.44 (3H, s),
1.98 (3H, s); 13C NMR (CD3OD, 125 MHz) δ 174.0, 146.5, 134.4
(2C), 131.0 (2C), 129.1, 101.4, 71.7, 71.2, 70.3, 68.3, 55.3, 54.2,
22.5, 21.6; EI-MS m/z 389 [M]+, 358, 340, 43 (base); HREI-
MS m/z 389.1158 (389.1149 calcd for C16H23NO8S).
ddt, J ) 12.8, 5.2, 1.5 Hz), 4.16 (0.5H, ddt, J ) 12.9, 5.2, 1.5
Hz), 4.11 (0.5H, dd, J ) 9.3, 5.9 Hz), 4.08 (0.5H, t, J ) 8.0
Hz), 3.99-4.05 (1H, m), 3.96 (0.5H, dd, J ) 9.3, 8.2 Hz), 3.88
(0.5H, dd, J ) 9.3, 6.2 Hz), 2.14 (1.5H, s), 2.13 (1.5H, s), 2.05
(1.5H, s), 2.03 (1.5H, s); 13C NMR (CDCl3, 125 MHz, all signals
correspond to 0.5C) δ 170.1, 170.0, 169.9, 169.9, 133.8, 133.6,
117.3, 117.2, 108.8, 100.3, 80.6, 80.1, 80.0, 79.6, 73.5, 72.6, 70.7,
68.7, 68.6, 68.4, 57.0, 54.7, 23.1, 23.0, 20.6, 20.5; EI-MS m/z
286 [M + H]+, 244, 226, 202, 43 (base); HREI-MS m/z 286.1297
(286.1289 calcd for C13H20NO6).
Meth yl 2-a ceta m id o-2-d eoxy-6-O-tosyl-â-D-m a n n op y-
r a n osid e (12b). By the use of 11b (99.8 mg, 0.276 mmol) as
a substrate, 12b (41.7 mg, 40%) was afforded in the same
manner as the synthesis of 5a . 12b: colorless needles; 1H NMR
(CD2Cl2, 500 MHz) δ 7.78 (2H, d, J ) 8.4 Hz), 7.37 (2H, d, J
) 8.4 Hz), 4.76 (1H, d, J ) 3.9 Hz), 4.29 (1H, dd, J ) 5.4, 3.3
Hz), 4.21-4.24 (2H, m), 4.02-4.08 (2H, m), 3.89 (1H, dd, J )
8.0, 3.3 Hz), 3.26 (3H, s), 2.42 (3H, s), 1.97 (3H, 2); 13C NMR
(CD2Cl2, 125 MHz) δ 172.0, 145.7, 133.0, 130.3 (2C), 128.3 (2C),
108.3, 79.6, 72.5, 70.9, 67.9, 58.7, 55.6, 22.8, 21.6; EI-MS m/z
372 [M - H2O + H]+, 340, 172, 91 (base), 43; HREI-MS m/z
372.1093 (389.1116 calcd for C16H22NO7S); FAB-MS m/z 390
[M + H]+.
Meth yl 2-a ceta m id o-3,6-a n h yd r o-2-d eoxy-â-D-m a n n o-
fu r a n osid e (13). 12a (40.4 mg, 0.104 mmol) in methanol (1
mL) was treated with sodium methoxide (22.4 mg, 0.415 mmol)
and stirred for 4 h at room temperature. The mixture was
acidified with Dowex 50w (H+), until the pH reached 3, and
stirred for 3 h. The solvent was evaporated, and the residue
was purified by SiO2 column chromatography (chloroform-
methanol, 95:5) to give 13 (16.8 mg, 74%).
By the use of 12b (31.2 mg, 0.080 mmol) as a substrate, 13
(15.3 mg, 88%) was afforded in the same manner as described
above. 13: colorless needles; 1H NMR (CD2Cl2, 500 MHz) δ
4.84 (1H, d, J ) 2.1 Hz), 4.59-4.64 (2H, m), 4.18-4.24 (2H,
m), 3.89 (1H, dd, J ) 9.3, 5.2 Hz), 3.73 (1H, dd, J ) 9.3, 5.2
Hz), 3.34 (3H, s), 1.96 (3H, s); 13C NMR (CD2Cl2, 125 MHz) δ
171.7, 111.0, 82.3, 80.7, 74.4, 71.4, 57.1, 55.5, 22.8; EI-MS m/z
218 [M + H]+, 185, 158, 128, 43 (base); HREI-MS m/z 218.1043
(218.1027 calcd for C9H16NO5).
Allyl 2-a ceta m id o-3,6-a n h yd r o-2-d eoxy-5-O-isova ler yl-
D-m a n n ofu r a n osid e (15). By the use of 14 (65.4 mg, 0.229
mmol) as a substrate, 15 (mixture of R and â-anomers, 1:1,
64.1 mg, 86%) was afforded in the same manner as the
synthesis of 8a . 15: a colorless oil; 1H NMR (CDCl3, 500 MHz)
δ 6.15 (0.5H, br.s), 6.13 (0.5H, br.s), 5.84-5.95 (1H, m), 5.28
(0.5H, dq, J ) 17.2, 1.6 Hz), 5.27 (0.5H, dq, J ) 17.2, 1.6 Hz),
5.16-5.21 (1.5H, m), 5.07 (0.5H, d, J ) 1.8 Hz), 5.07 (0.5H, d,
J ) 5.2 Hz), 5.01 (0.5H, ddd, J ) 9.5, 8.0, 5.4 Hz), 4.86 (0.5H,
t, J ) 5.1 Hz), 4.84 (0.5H, t, J ) 5.0 Hz), 4.73 (0.5H, dd, J )
6.6, 5.0 Hz), 4.61 (0.5H, dd, J ) 5.6, 5.0 Hz), 4.49 (0.5H, dt, J
) 8.8, 5.6 Hz), 4.33 (0.5H, td, J ) 6.6, 1.8 Hz), 4.28 (0.5H,
ddt, J ) 12.9, 5.3, 1.5 Hz), 4.15 (0.5H, ddt, J ) 12.9, 5.3, 1.5
Hz), 4.10 (0.5H, dd, J ) 9.4, 5.8 Hz), 4.08 (0.5H, t, J ) 8.0
Hz), 4.01 (0.5H, dq, J ) 12.9, 1.3 Hz), 4.00 (0.5H, dq, J ) 12.9,
1.3 Hz), 3.94 (0.5H, dd, J ) 9.5, 8.0 Hz), 3.90 (0.5H, dd, J )
9.4, 6.0 Hz), 2.20-2.30 (2H, m), 2.09-2.17 (1H, m), 2.05 (1.5H,
s), 2.03 (1.5H, s), 0.99 (1.5H, d, J ) 6.6 Hz), 0.98 (4.5H, d, J )
6.6 Hz); 13C NMR (CDCl3, 125 MHz, all signals correspond to
0.5C) δ 172.3, 172.0, 169.9, 169.9, 133.8, 133.6, 117.3, 117.3,
108.8, 100.3, 80.7, 80.1, 80.0, 79.7, 73.3, 72.3, 70.9, 68.7, 68.5,
68.2, 57.0, 54.7, 43.0, 43.0, 25.7, 25.7, 23.1, 23.1, 22.4, 22.3,
22.3, 22.2; EI-MS m/z 328 [M + H]+, 286, 268, 253, 85 (base),
57, 43; HREI-MS m/z 328.1789 (328.1759 calcd for C16H26NO6).
2-Acetam ido-3,6-an h ydr o-2-deoxy-5-O-isovaler yl-D-m an -
n ofu r a n ose (fu r a n od ictin e B) (2). By the use of15 (43.9 mg,
0.136 mmol) as a substrate, 2 (19.7 mg, 50%) was afforded in
the same manner as the synthesis of 1. Synthetic 2: [R]25
D
+98.4 (c 0.808, CHCl3); other spectral data were identical with
those of the natural product.
Allyl 2-a cet a m id o-5-O-a cet yl-3,6-a n h yd r o-2-d eoxy-D-
m a n n ofu r a n osid e (14). By the use of 13 (201 mg, 0.925
mmol) as a substrate, 14 (mixture of R and â-anomers, 1:1,
252 mg, 95%) was afforded in the same manner as the
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for Scientific Research (No. 12470474)
from the Ministry of Education, Science, Sports, and
Culture of J apan.
1
synthesis of 7a and 7b. 14: a colorless oil; H NMR (CDCl3,
500 MHz) δ 6.14 (0.5H, br.s), 6.13 (0.5H, br.s), 5.85-5.96 (1H,
m), 5.29 (0.5H, dq, J ) 17.2, 1.5 Hz), 5.27 (0.5H, dq, J ) 17.3,
1.5 Hz), 5.16-5.22 (1.5H, m), 5.08 (0.5H, d, J ) 1.9 Hz), 5.07
(0.5H, d, J ) 5.6 Hz), 5.01 (0.5H, ddd, J ) 9.3, 7.9, 5.6 Hz),
4.85 (0.5H, t, J ) 5.2 Hz), 4.83 (0.5H, t, J ) 5.0 Hz), 4.72 (0.5H,
dd, J ) 6.5, 5.0 Hz), 4.61 (0.5H, dd, J ) 5.6, 4.9 Hz), 4.49 (0.5H,
dt, J ) 8.9, 5.6 Hz), 4.34 (0.5H, td, J ) 6.5, 1.9 Hz), 4.28 (0.5H,
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for natural and synthetic compounds 1 and 2 and their
biological data. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O015657X