Novel and facile synthesis of furanodictines A and B based on transformation of 2-acetamido-2-deoxy-d-glucose into 3,6-anhydro hexofuranoses

Article abstract of DOI:10.1016/j.carres.2009.10.007

A novel synthesis of furanodictines A [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-d-glucofuranose (1)] and B [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-d-mannofuranose (2)] is described starting from 2-acetamido-2-deoxy-d-glucose (GlcNAc). The synthetic protocol is based on deriving the epimeric bicyclic 3,6-anhydro sugars [2-acetamido-3,6-anhydro-2-deoxy-d-glucofuranose (4) and 2-acetamido-3,6-anhydro-2-deoxy-d-mannofuranose (5)] from GlcNAc. Reaction with borate upon heating led to a facile transformation of GlcNAc into the desired epimeric 3,6-anhydro sugars. The C5 hydroxyl group of the 3,6-anhydro compounds 4 and 5 was regioselectively esterified with the isovaleryl chloride to complete the synthesis of furanodictines A and B, respectively. The targets 1 and 2 were synthesized in only two steps requiring no protection/deprotection.

Full text of DOI:10.1016/j.carres.2009.10.007

Carbohydrate Research 345 (2010) 230–234
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Novel and facile synthesis of furanodictines A and B based on transformation
of 2-acetamido-2-deoxy-D-glucose into 3,6-anhydro hexofuranoses
Makoto Ogata a,b, Takeshi Hattori b, Ryota Takeuchi b, Taichi Usui a,b,
*
a Department of Bioscience, Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga ward, Shizuoka 422-8529, Japan
b Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Ohya 836, Suruga ward, Shizuoka 422-8529, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel synthesis of furanodictines A [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-D-glucofuranose
Received 7 August 2009
Received in revised form 23 September
2009
Accepted 11 October 2009
Available online 2 December 2009
(1)] and B [2-acetamido-3,6-anhydro-2-deoxy-5-O-isovaleryl-
from 2-acetamido-2-deoxy- -glucose (GlcNAc). The synthetic protocol is based on deriving the epimeric
bicyclic 3,6-anhydro sugars [2-acetamido-3,6-anhydro-2-deoxy- -glucofuranose (4) and 2-acetamido-
3,6-anhydro-2-deoxy- -mannofuranose (5)] from GlcNAc. Reaction with borate upon heating led to a fac-
D-mannofuranose (2)] is described starting
D
D
D
ile transformation of GlcNAc into the desired epimeric 3,6-anhydro sugars. The C5 hydroxyl group of the
3,6-anhydro compounds 4 and 5 was regioselectively esterified with the isovaleryl chloride to complete
the synthesis of furanodictines A and B, respectively. The targets 1 and 2 were synthesized in only two
steps requiring no protection/deprotection.
Keywords:
2-Acetamido-2-deoxy-D-glucose
Bicyclic 3,6-anhydroaminosugar
3,6-Anhydrohexofuranose
Furanodictines A and B
Ó 2009 Elsevier Ltd. All rights reserved.
GlcNAc transformation
1. Introduction
2. Results and discussion
Oshima and co-workers isolated the 3,6-anhydro amino sugar
derivatives, furanodictines A (1) and B (2) from the metabolic ex-
tract of the fruiting body of the cellular slime mold Dictyostelium
discoideum (Fig. 1).1 Both these compounds display potent neuro-
nal differentiation activity in rat PC-12 cells.1,2 The absolute config-
urations of furanodictines A and B were confirmed by asymmetric
syntheses of 1 and 2, which possess a 3,6-anhydro hexofuranose
carbon skeleton corresponding to 4 and 5, respectively. Furanodic-
tines A (1) and B (2) are the first examples of amino sugars with an
interesting bicyclic bis-tetrahydrofurofuran structure. The struc-
tural complexity, coupled with the potent biological activity,
makes 1 and 2 attractive targets for total synthesis.3–5 Although to-
tal synthesis has been achieved, these synthetic procedures gener-
ally require multi-step pathways and are unsatisfactory for
obtaining the target compounds in reasonable yield. There is an ur-
gent need to prepare large quantities of such pharmacophore-con-
taining compounds from easily available raw materials by simple
methods. Here a simple synthetic strategy for 1 and 2 starting from
readily available GlcNAc was designed and executed.
2.1. Transformation of GlcNAc into hexofuranoses
The reaction was initially carried out at a concentration of Glc-
NAc (100 mM) in borate solution (pH 7.0) at 100 °C for 2 h. The
reaction mixture was applied to a column of charcoal–Celite with
a linear gradient of ethanol as shown in Figure 2. The chromato-
gram showed five fractions (F-1–F-5), numbered according to the
order of elution. Each fraction was collected and analyzed sepa-
rately. Fraction 1 contained GlcNAc and 2-acetamido-2-deoxy-D-
mannose (ManNAc) in a proportion of 2:1, respectively, in a yield
of 10%. Fraction 2 was not identified. Fractions 3, 4, and 5 were ob-
tained in actual yields of 9.8%, 10.2%, and 36%, respectively, and
identified as the respective unsaturated derivative 3 (F-5) and
two epimeric 3,6-anhydro derivatives 4 (F-4) and 5 (F-3). In the
O
H
O
O
OH
O
H
Y
X
X = H, Y = NHAc: furanodictine A (1)
X = NHAc, Y = H: furanodictine B (2)
* Corresponding author. Tel./fax: +81 54 238 4873.
E-mail address: actusui@agr.shizuoka.ac.jp (T. Usui).
Figure 1. Structures of furanodictines A and B.
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.10.007

M. Ogata et al. / Carbohydrate Research 345 (2010) 230–234
231
100
80
60
40
20
0
F-5
(a) GlcNAc
25
20
15
10
5
1.8
1.6
1.4
1.2
1
F-1
F-4
F-3
F-2
0.8
0.6
0.4
0.2
0
0
210
50
70
90
110
130
150
170
190
Fraction No. (60 mL each)
0
50
100
150
200
250
Figure 2. Charcoal–Celite chromatography of products formed from GlcNAc
Reaction time (min)
transformation. Dotted line, concentration of ethanol in gradient elution (%).
100
80
60
40
20
0
(b) ManNAc
Morgan–Elson reaction, Chromogen I (2-acetamido-2,3-dideoxy-D-
erythro-hex-2-enofuranose, 3) is known to be the major chromo-
gen formed by alkali treatment of GlcNAc under the conditions
used by Kuhn and Kruger.6,7 Sinay and co-workers have established
that the major Chromogen I of the Morgan–Elson reaction is the
structure 3, which was derived in four steps from ManNAc.8 Com-
pound 3 was produced in preference to epimeric 3,6-anhydro
forms 4 and 5.9 Derevitskaya et al. have reported that the epimeric
4 and 5 are formed in low yields during the alkaline degradation of
GlcNAc, based on the Morgan–Elson reaction. Compounds 4 and 5
are formed in a 1:1 ratio during the entire course of the reaction.
These results indicated that about two-thirds of the GlcNAc start-
ing material is converted into a series of hexofuranose derivatives.
The structures of these compounds were evaluated by 1H and 13C
NMR analyses in D2O solution, and were consistent with published
data.8,10 In addition, ESI-MS analysis was also carried out on each
fraction. The same molecular ion at m/z 226 was obtained for 3,
4, and 5 arising from the [M+Na]+ ion of GlcNAc with loss of mass
corresponding to a water molecule. As a result, we established a
facile transformation of GlcNAc into 4 and 5, which is useful for
the synthesis of furanodictines A and B.
0
50
100
150
200
250
Reaction time (min)
Figure 3. HPLC analyses of GlcNAc/ManNAc on transformation in borate solution
(pH 7.0) upon heating. Time–course of products 3, 4, and 5 on transformation
formed from GlcNAc/ManNAc. (a) GlcNAc. (b) ManNAc. Filled diamond, GlcNAc;
filled square, ManNAc; open circle, 3; open diamond, 4; open square, 5.
group.11 In addition, when GlcNAc was boiled in water as a control
experiment, three compounds 3, 4, and 5 were also produced,
although in extremely low total yields (5%).
Each of the products 3–5 was reacted again under the same con-
ditions and analyzed by HPLC. Whichever compound was chosen
(i.e., 3, 4, or 5), the same products were generated during the reac-
tion. For example, starting with 4, 85% of 4 was converted to 3, 5,
GlcNAc and ManNAc after 120 min in a ratio of 4.4:1.0:0.7:0.3,
2.2. Time–course analysis of GlcNAc transformation in borate
solution
A time–course study of the GlcNAc transformation was carried
out in borate solution with heating as described above. HPLC peaks
corresponding to 3, 4, and 5 appeared at retention times of 8.5, 5.7,
and 5.1 min, respectively (see Section 4). The time for maximum
formation of 3, 4, and 5 was reached at ꢀ2 h and their concentra-
tions varied little upon further reaction (Fig. 3a). Compounds 3, 4,
and 5 were obtained in a total analytical yield of about 80% and in a
ratio of 4.7:1:1, respectively. Compound 3 formed in preference to
4 and 5, which were produced in equal amount during the entire
course of the reaction. GlcNAc and ManNAc were in part epimer-
ized to each other during the reaction process.11–13 When ManNAc
was used instead of GlcNAc as a starting material, three products 3,
4, and 5 were generated in a similar ratio and yield (Fig. 3b). Little
color was produced at pH 7, but browning occurred at pH values
greater than 8. Indeed, as the pH of the reaction increased above
8 there was a significant deepening in this coloration accompanied
by an increase in the proportion of unknown products other than
the three hexofuranoses (data not shown). Thus, the 2-amino sug-
ars rapidly decompose in alkaline solution upon heating to give a
multitude of products followed by a browning reaction.8 Proximity
of the amino group to the anomeric center in 2-amino-sugars con-
fers special properties, which are unusual in the carbohydrate
100
80
60
40
20
0
0
50
100
150
200
250
Reaction time (min)
Figure 4. Time–course of products 3, 5, GlcNAc, and ManNAc on transformation in
borate solution (pH 7.0) upon heating formed from 4. Filled diamond, GlcNAc; filled
square, ManNAc; open circle, 3; open diamond, 4; open square, 5.

232
M. Ogata et al. / Carbohydrate Research 345 (2010) 230–234
OH
B
HO
CH2OH
H
O
O
O
H
OH
O
O
OH
-H2O
OH
OH
H
O
H
H
OH
O
H
NHAc
NHAc
NHAc
4
GlcNAc
HO
HO
H
H
H
+H2O
+H2O
O
OH
H
C
OH
OH
OH
O
NHAc
NHAc
3
OH
B
CH2OH
O
HO
H
H
O
O
H
OH
-H2O
OH
O
OH
O
NHAc
OH
NHAc
OH
H
O
H
O
H
NHAc
ManNAc
5
Scheme 1. Proposed mechanism of transformation of GlcNAc/ManNAc into 3, 4, and 5 in borate solution upon heating.
respectively, and their concentrations varied little after prolonged
reaction (Fig. 4). These results suggest that the transformation of
GlcNAc into 3–5 is a reversible reaction.
The present reaction is proposed to account for a series of
hexofuranose transformations as shown in Scheme 1. Despite the
complexity of the system, considerable attention has been focused
on the reaction of borates with carbohydrates and boron.14 Triden-
MS analysis of 1 and 2 showed molecular ions at m/z 310.12710
and 310.12707, respectively, arising from the [M+Na]+ ions. Thus,
the target products 1 and 2 were conveniently synthesized in only
a two-step process. The spectral data of synthetic 1 and 2 were
identical to those of the natural products.1
3. Conclusions
tate complexes with borate at 3-, 5-, and 6-hydroxyl groups of D-
glucofuranose have been studied previously.15 The formation of a
borate complex from glucose might facilitate its conversion from
the pyranose to the furanose form in borate solution upon heating.
Indeed, formation of the complex facilitates abstraction of the 2-
hydrogen substituent to give 3 followed by dehydration with one
water molecule. The resulting 3 undergoes a ready epimerization
to afford 4 and 5 in an equal amount, suggesting that they proceed
through 2-enol as intermediate by consecutive electron displace-
ment involving intramolecular attack of HO-6 at C-3 in 3. Which-
ever compound was chosen (i.e., 3–5 or GlcNAc), the reaction
profiles were indistinguishable in the equilibrium state. We there-
fore conclude that the GlcNAc transformation is a reversible reac-
tion followed by consecutive dehydration and epimerization.
In conclusion, a total synthesis of furanodictines A and B has
been executed via a two-step process starting from readily avail-
able GlcNAc. Our process comprises a new synthetic strategy that
does not necessitate protection/deprotection. As a result, a facile
transformation of GlcNAc into 4 and 5 with a 3,6-anhydro hexof-
uranose carbon skeleton offers a promising approach towards the
mass production of furanodictines A and B.
4. Experimental
4.1. General methods
GlcNAc and isovaleryl chloride were purchased from Sigma–Al-
drich (St. Louis, MO). All other reagents were of the highest quality
commercially available and were used without further purification.
2.3. Syntheses of furanodictines A (1) and B (2)
The ability to generate large quantities of 4 and 5 facilitated the
synthesis of furanodictines A and B. Compounds 4 and 5 were di-
rectly converted to furanodictines A (1) and B (2) as shown in
Scheme 2. The C5 hydroxy group in 4 and 5 was regioselectively
esterified with isovaleryl chloride in dry pyridine to complete the
total synthesis of 1 and 2, respectively. The target products 1 and
2 were purified by chromatography on silica gel and ODS column
to give yields of 30% and 28%, respectively, based on the amount
of 4 and 5. The structures of these compounds were evaluated by
1H and 13C NMR analyses in CDCl3 solution. In addition, HRESI-
4.2. Analytical methods
HPLC analysis was carried out using a Unison UK-Amino col-
umn (4.6 ꢁ 250 mm, Imtakt) with a JASCO Intelligent system liquid
chromatograph and detection at 210 nm. The bound material was
eluted with 95% CH3CN at a flow rate of 1.0 mL/min at 40 °C. The
ESI-MS spectra were measured on a JMS-T100LC mass spectrome-
ter. 1H and 13C NMR spectra were recorded on a JEOL JNM-LA 500
spectrometer at 25 °C. Chemical shifts are expressed in d relative to
sodium 3-(trimethylsilyl) propionate as an external standard.
HO
O
H
H
4.3. Transformation of GlcNAc into hexofuranoses
O
O
O
a
OH
OH
GlcNAc (5.52 g, 25 mmol) dissolved in 0.4 M borate buffer (pH
7.0, 250 mL) was incubated for 2 h at 100 °C. The mixture was then
loaded onto a charcoal–Celite column (4.5 ꢁ 100 cm) equilibrated
with distilled water. Subsequently, the adsorbed portion was
eluted with a linear gradient of 0–25% ethanol in a total volume
of 10 L, followed by 25% ethanol, at a flow rate of 4.7 mL/min. Frac-
tions (60 mL/tube) were collected during the elution of material
from the column. The chromatogram identified five distinct peaks.
O
O
H
Y
H
Y
X
X
X = H, Y = NHAc (
X = NHAc, Y = H (
4
5
)
)
X = H, Y = NHAc: furanodictine A (
X = NHAc, Y = H: furanodictine B (2
1
)
)
Scheme 2. Syntheses of furanodictines A and B. Reagents and conditions: (a) dry
pyridine, isovaleryl chloride, 25 °C, 2 h, 30% (1), 28% (2).

M. Ogata et al. / Carbohydrate Research 345 (2010) 230–234
233
Fractions corresponding to each of the five peaks, F-1 to F-5, were
pooled, concentrated, and lyophilized. F-1 (fractions 73–86) con-
tained 520 mg as a mixture of GlcNAc and ManNAc in a ratio of
2:1, respectively. F-3 (fractions 121–128) was obtained as 2-acet-
and dissolved in 1.0 mL of H2O and then loaded onto a ODS column
(1.5 ꢁ 30 cm). The bound compound was eluted with a linear gra-
dient of 0–30% MeOH in a total volume of 1.2 L at a flow rate of
2.0 mL/min, and a fraction size of 15 mL/tube. Fractions 70–76
were pooled and concentrated. Furanodictine A (1) was obtained
in a total yield of 30% (64 mg) as a colorless oil. Compound 1
amido-3,6-anhydro-2-deoxy-
D
-mannofuranose (5, 495 mg, 9.8%),
-anomer, mp 169–
+151.5 (c 1.0, water); HRESIMS: m/z 226.06938
which was crystallized from ethanol;9
a
170 °C; ½a 2D7
ꢂ
was a mixture of two anomers (
+116.3 (c 0.8, CHCl3); HRESIMS: m/z 310.12710 [M+Na]+ (calcd
for C13H21N1Na1O6, 310.12666); 1H NMR (CDCl3, 500 MHz)
-ano-
a/b = 6.8/1); Rf = 0.20 (EtOAc);
[M+Na]+ (calcd for C8H13N1Na1O5, 226.06914); 1H NMR (D2O,
½ ꢂ
a 2D5
500 MHz, the spectrum was measured after 2 h)
a
-anomer: d
a
5.53 (d, 1H, J1,2 = 5.5 Hz, H-1), 4.70 (t, 1H, J3,4 = 5.5, J4,5 = 5.5 Hz,
H-4), 4.65–4.62 (1H, H-3), 4.42–4.38 (1H, H-5), 4.35 (t, 1H,
J1,2 = 5.5, J2,3 = 5.5 Hz, H-2), 3.96–3.89 (2H, H-6b, H-6a), 2.07 (s,
3H, CH3CONH–); b-anomer: d 5.31 (d, 1H, J1,2 = 6.0 Hz, H-1), 4.81
(t, 1H, J3,4 = 4.6, J4,5 = 4.6 Hz, H-4), 4.65–4.62 (1H, H-3), 4.42–4.38
(1H, H-5), 4.25 (t, 1H, J1,2 = 6.0, J2,3 = 6.0 Hz, H-2), 4.02 (dd, 1H,
J5,6b = 6.7, J6a,6b = 8.4 Hz, H-6b), 3.55 (t, 1H, J5,6a = 8.4, J6a,6b = 8.4 Hz,
mer: d 6.40 (d, 1H, JNH,2 = 7.5 Hz, NH), 5.50 (d, 1H, J1,2 = 4.5 Hz, H-
1), 4.95 (ddd, 1H, J4,5 = 5.5, J5,6a = 8.0, J5,6b = 6.0 Hz, H-5), 4.84 (t,
1H, J3,4 = 5.5, J4,5 = 5.5 Hz, H-4), 4.52 (dd, 1H, J2,3 = 4.0,
J3,4 = 5.5 Hz, H-3), 4.33 (m, 1H, H-2), 4.01 (dd, 1H, J5,6b = 6.0,
J6a,6b = 9.0 Hz, H-6b), 3.77 (dd, 1H, J5,6a = 8.0, J6a,6b = 9.0 Hz, H-6a),
2.25–2.17 (2H, CH2), 2.10–2.02 (1H, CH), 1.99 (s, 3H, CH3CONH–),
0.92 (d, 6H, CH3); b-anomer: d 5.50 (br s, 1H, NH), 5.22 (br s, 1H,
H-1), 5.04 (ddd, 1H, J4,5 = 5.0, J5,6a = 6.0, J5,6b = 4.5 Hz, H-5), 4.87
(t, 1H, J3,4 = 5.0, J4,5 = 5.0 Hz, H-4), 4.38 (1H, H-3), 4.17 (m, 1H, H-
2), 4.09 (dd, 1H, J5,6b = 4.5, J6a,6b = 9.5 Hz, H-6b), 3.89 (dd, 1H,
J5,6a = 6.0, J6a,6b = 9.5 Hz, H-6a), 2.25–2.17 (2H, CH2), 2.10–2.02
(1H, CH), 1.96 (s, 3H, CH3CONH–), 0.92 (d, 6H, CH3); 13C NMR
H-6a), 2.05 (s, 3H, CH3CONH–); 13C NMR (D2O, 125 MHz)
a-ano-
mer: d 177.0 (CH3CONH–), 98.3 (C-1), 84.7 (C-4), 83.0 (C-3),
73.95 (C-5), 73.5 (C-6), 57.5 (C-2), 24.4 (CH3CONH–); b-anomer:
d 177.2 (CH3CONH–), 103.7 (C-1), 83.5 (C-4), 82.7 (C-3), 74.3 (C-
5), 73.90 (C-6), 61.8 (C-2), 24.5 (CH3CONH–). F-4 (fractions 132 ꢀ
139) was obtained as 2-acetamido-3,6-anhydro-2-deoxy-
D
-gluco-
(CDCl3, 125 MHz) a
-anomer: d 172.6 (C0-1), 170.8 (CH3CONH–),
furanose (4, 516 mg, 10.2%), which was crystallized from ethyl ace-
98.0 (C-1), 86.9 (C-3), 77.7 (C-4), 72.2 (C-5), 68.6 (C-6), 58.6 (C-
2), 42.9 (C0-2), 25.6 (C0-3), 23.0 (CH3CONH–), 22.3 (C0-4, C0-5); b-
anomer: d 172.8 (C0-1), 170.6 (CH3CONH–), 103.4 (C-1), 86.5 (C-
3), 81.6 (C-4), 73.1 (C-5), 70.6 (C-6), 61.2 (C-2), 42.8 (C0-2), 25.4
(C0-3), 22.9 (CH3CONH–), 22.3 (C0-4, C0-5). Furanodictine B (2)
was obtained in a similar manner with a total yield of 28%
(59 mg) as a colorless oil from compound 5 and isovaleryl chloride.
tate. Compound 4 was a mixture of two anomers (
a
/b = 2/1); m.p.
124–125 °C; ½a 2D7
ꢂ
+104.5 (c 1.0, water); HRESIMS: m/z 226.07013
[M+Na]+ (calcd for C8H13N1Na1O5, 226.06914); 1H NMR (D2O,
500 MHz)
a-anomer: d 5.62 (d, 1H, J1,2 = 5.0 Hz, H-1), 4.76 (t, 1H,
J3,4 = 5.0, J4,5 = 5.0 Hz, H-4), 4.66 (t, 1H, J2,3 = 5.0, J3,4 = 5.0 Hz, H-3),
4.33–4.29 (1H, H-5), 4.27 (t, 1H, J1,2 = 5.0, J2,3 = 5.0 Hz, H-2), 4.00
(dd, 1H, J5,6b = 6.5, J6a,6b = 8.5 Hz, H-6b), 3.66 (t, 1H, J5,6a = 8.5,
J6a,6b = 8.5 Hz, H-6a), 2.06 (s, 3H, CH3CONH–); b-anomer: d 5.44
(1H, H-1), 4.79 (t, 1H, J3,4 = 5.0, J4,5 = 5.0 Hz, H-4), 4.52 (d, 1H,
J3,4 = 5.0 Hz, H-3), 4.33–4.29 (1H, H-5), 4.18 (1H, H-2), 3.96 (t, 1H,
J5,6b = 8.0, J6a,6b = 8.0 Hz, H-6b), 3.88 (t, 1H, J5,6a = 8.0, J6a,6b = 8.0 Hz,
Compound 2 was a mixture of two anomers (
a
/b = 1/2.5); Rf = 0.21
(EtOAc); ½a 2D5
ꢂ
+103.9 (c 0.8, CHCl3); HRESIMS: m/z 310.12707
[M+Na]+ (calcd for C13H21N1Na1O6, 310.12666); 1H NMR (CDCl3,
500 MHz)
a-anomer: d 6.16 (d, 1H, JNH,2 = 7.5 Hz, NH), 5.17 (d,
1H, J1,2 = 4.0 Hz, H-1), 5.10 (td, 1H, J4,5 = 5.0, J5,6a = 5.5,
J5,6b = 5.5 Hz, H-5), 4.90 (t, 1H, J3,4 = 5.0, J4,5 = 5.0 Hz, H-4), 4.55
(dd, 1H, J2,3 = 6.5, J3,4 = 5.0 Hz, H-3), 4.15 (m, 1H, H-2), 4.00 (dd,
1H, J5,6b = 5.5, J6a,6b = 9.5 Hz, H-6b), 3.76 (dd, 1H, J5,6a = 5.5,
J6a,6b = 9.5 Hz, H-6a), 2.25–2.16 (2H, CH2), 2.09–2.01 (1H, CH),
1.98 (s, 3H, CH3CONH–), 0.92–0.90 (6H, CH3); b-anomer: d6.16
(d, 1H, JNH,2 = 7.5 Hz, NH), 5.32 (br s, 1H, H-1), 5.04 (td, 1H,
J4,5 = 5.5, J5,6a = 6.5, J5,6b = 6.5 Hz, H-5), 4.86 (dd, 1H, J3,4 = 5.0,
J4,5 = 5.5 Hz, H-4), 4.47 (1H, H-3), 4.37 (m, 1H, H-2), 4.03 (dd, 1H,
J5,6b = 6.5, J6a,6b = 9.0 Hz, H-6b), 3.92 (dd, 1H, J5,6a = 6.5,
J6a,6b = 9.0 Hz, H-6a), 2.25–2.16 (2H, CH2), 2.09–2.01 (1H, CH),
1.99 (s, 3H, CH3CONH–), 0.92–0.90 (6H, CH3); 13C NMR (CDCl3,
H-6a), 2.02 (s, 3H, CH3CONH–); 13C NMR (D2O, 125 MHz)
a-ano-
mer: d 177.1 (CH3CONH–), 100.4 (C-1), 88.5 (C-3), 81.7 (C-4),
73.0 (C-5, C-6), 61.5 (C-2), 24.56 (CH3CONH–); b-anomer: d 176.8
(CH3CONH–), 105.2 (C-1), 88.6 (C-3), 85.6 (C-4), 73.8 (C-6), 73.5
(C-5), 64.7 (C-2), 24.60 (CH3CONH–). F-5 (fractions 162–197) was
obtained as Chromogen I (3) in the form of a syrupy liquid (1.8 g,
36%). Compound 3 was a mixture of two anomers (
+14.8 (c 1.0, water); HRESIMS: m/z 226.06893 [M+Na]+ (calcd
for C8H13N1Na1O5, 226.06914); 1H NMR (D2O, 500 MHz)
-ano-
a/b = 1.6/1);
½ ꢂ
a 2D7
a
mer: d 6.16 (1H, H-3), 6.04 (1H, H-1), 5.06 (1H, H-4), 3.83–3.57
(3H, H-5, H-6b, H-6a), 2.13 (s, 3H, CH3CONH–); b-anomer: d 6.21
(1H, H-3), 5.99 (1H, H-1), 4.83 (1H, H-4), 3.83–3.57 (3H, H-5, H-
125 MHz) a
-anomer: d 172.2 (C0-1), 171.0 (CH3CONH–), 103.5 (C-
6b, H-6a), 2.13 (s, 3H, CH3CONH–); 13C NMR (D2O, 125 MHz)
a
-
1), 80.3 (C-3), 79.6 (C-4), 72.8 (C-5), 70.7 (C-6), 58.9 (C-2), 42.9
(C0-2), 25.6 (C0-3), 23.1 (CH3CONH–), 22.3 (C0-4, C0-5); b-anomer:
d 172.3 (C0-1), 170.3 (CH3CONH–), 96.4 (C-1), 80.7 (C-3), 80.6 (C-
4), 73.4 (C-5), 69.7 (C-6), 54.6 (C-2), 42.8 (C0-2), 25.5 (C0-3), 23.0
(CH3CONH–), 22.3 (C0-4, C0-5).
anomer: d 176.1 (CH3CONH–), 137.0 (C-2), 112.0 (C-3), 102.2 (C-
1), 87.5 (C-4), 76.2 (C-5), 65.2 (C-6), 25.4 (CH3CONH–); b-anomer:
d 176.1 (CH3CONH–), 136.5 (C-2), 112.7 (C-3), 102.0 (C-1), 87.2 (C-
4), 76.5 (C-5), 65.1 (C-6), 25.4 (CH3CONH–).
4.4. Syntheses of furanodictines A (1) and B (2)
Acknowledgment
Compound 4 (150 mg, 0.74 mmol) was dissolved in dry pyridine
(5.0 mL) at 0 °C. Isovaleryl chloride (90 lL, 0.74 mmol) was added
This work was supported by the Programme for Promotion of
Basic and Applied Researches for Innovations in Bio-oriented
Industry in Japan.
to the solution, and then the mixture was stirred magnetically
for 2 h at room temperature. The reaction was terminated by add-
ing crushed ice. After three extractions with CHCl3, the organic
layer was washed with saturated sodium bicarbonate solution,
water and brine, and then dried over anhydrous sodium sulfate be-
fore being concentrated. The reaction products were dissolved in
1.0 mL of CHCl3/MeOH = 27:1 and then loaded onto a Silica Gel
60 N column (2.0 ꢁ 40 cm). The column was developed with the
same solvent at a flow rate of 10 mL/min and a fraction size of
15 mL/tube. An aliquot from fractions 36–50 was concentrated
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