2
J.W. Kim et al. / Tetrahedron Letters xxx (xxxx) xxx
malfilamentoside B whose stereochemistry was unassigned in
tone chromophore. The corresponding n-p* and p-p* transitions in
the original report [9]. Malfilamentoside B and its dehydroxylated
derivative malfilamentoside A isolated from Malbranchea filamen-
tosa are the only previously known example of furanone glycosides
produced by the fungal sources. We herein report the structures of
three furanone glycosides including their absolute configurations
defined by spectroscopic and chemical methods as well as VCD
calculations.
1 are not easily attributable because of overlapping of the
p-p*
transitions of the phenyl groups, which prevents us from applying
this rule. As the carbonyl group in furanones exhibits a character-
istic strong absorption band in the IR region [12–14], we measured
the IR and vibrational circular dichroism (VCD) spectra of 1 to gain
an insight into the absolute configuration at C-4. As shown in
Fig. 4a, two intense absorption bands were observed in the C@O
ꢀ1
stretching region. The higher wavenumber band at ca. 1770 cm
is attributable to the C@O stretching band of the lactone carbonyl
ꢀ1
Results and discussion
group, whereas the lower band at ca. 1660 cm can be assigned to
the amide C@O stretching band. A positive and negative VCD sig-
nals were observed for the lactone and amide C@O stretching
bands, respectively. Fig. 4b shows the calculated VCD spectra of
optimized structures of (4R)-1 and (4S)-1 in the carbonyl region.
The spectral data for (4R)-1 matched well with the experimental
data. The positive VCD signal was also calculated for the (4R)-fura-
none without the sugar moiety (Fig. S29). From these results, the
absolute configuration at C-4 was assigned to be R.
Compound 1 was isolated as a white amorphous powder that
gave a [M + Na]+ ion in the HRESIMS at m/z 522.1739, indicating
a molecular formula of C26H29NO Na. Structure determination
9
using a combination of 1D and 2D NMR techniques, including
COSY, HSQC, and HMBC, revealed that compound 1 has the identi-
cal planar structure with malfilamentoside B which possesses a
2
,3-aryl substituted furanone backbone with aminosugar linked
at C-4 (Fig. 1) [9]. The relative configuration of a sugar unit was
Compound 2 was obtained as a white amorphous powder. The
determined by analysis of vicinal 1H- H coupling ( JH,H) constants
1
3
molecular formula of 2 was deduced as C25
9
H27NO based on the
in conjunction with the ROESY spectroscopic data (Fig. 2). The large
analysis of HRESIMS in combination with NMR data (Table 1).
1
13
vicinal coupling constant of JH-2
0
,H-3
0
(10.5 Hz) assigned axial orien-
The H and C NMR spectra of 2 exhibited chemical shifts and
splitting patterns highly comparable to those of 1. The interpreta-
tion of the 2D NMR data, including COSY, HSQC, and HMBC spectra,
led to the construction of the planar structure of 2 (Fig. 1). The
tations. This interpretation was further supported by the ROESY
0
data in which the 1,3-diaxial cross-peaks were observed at H-2 /
0
0
0
0
H-4 and H-3 /H-5 . The equatorial position of H-1 was established
3
0
0
0
0
0
0
by the small coupling constant of JH-1
0
,H-2
0
(3.4 Hz) and the ROESY
correlation between H-1 and H-2 . The sugar moiety was therefore
defined to be 6-O-methyl-N-acetyl- -glucosamine. The absolute
cross-peaks of H-1 /H-2 /H-3 /H-4 /H-5 /H
2
0
-6 in the COSY spec-
0
0
0
trum showed the connectivity through C-1 to C-6 . The connectiv-
a
ity of an N-acetyl group was established by HMBC correlations of
0
0
0
stereochemistry at C-11 was assigned by the modified Mosher
3 C
H-2 and H -8 to the amide carbon C-7 (d 173.7). The determina-
1
ester analysis [10]. Because the difference in the H NMR chemical
tion of the aglycone structure of 2 was mainly achieved by inter-
pretation of HMBC correlations. Key HMBC correlations from one
distinctive proton H-4 for a acetal moiety (dC/H 103.4/6.31) to the
ester carbonyl C-1 and two olefinic non-protonated carbons C-2
shifts between S- and R-
a
-methoxy- -(trifluoromethyl)pheny-
a
lacetic acid (MTPA) esters (
and negative for H-13/17, a 11R configuration was determined
D
d
H
= d ) were positive for H-4
S
ꢀ d
R
0
(Fig. 3). Although another secondary alcohol at C-3 in the sugar
and C-3 suggested the presence of an a, b-unsaturated c-lactone
moiety was also esterified with MTPA, it was not possible to unam-
ring. Two mono-substituted benzene rings whose presence was
revealed by a combination of the 2D NMR data were then con-
nected to the aglycone moiety by three-bond HMBC correlations.
HMBC correlations from H-6/10 to C-2 placed one benzene ring
at C-2 as a substituent. The remaining benzene was proved to be
linked to C-3 via an oxymethine bridge C-11 from analysis of the
HMBC cross-peaks from H-13/17 to C-11 and from H-11 to carbons
in the aglycone moiety (C-2, C-3, and C-4). Lastly, obvious HMBC
0
biguously assign the absolute configuration of C-3 due to the same
0
0
positive
neous distributions). The absolute configuration of the sugar moi-
ety was determined to be on the basis of the sugar derivatization
H
Dd sign for both substituents H-2 and H-4 (nonhomoge-
D
experiments using 2 as discussed below.
Next, we attempted to establish the absolute stereochemistry at
C-4 in 1 by theoretical electronic circular dichroism (ECD) analysis.
An empirical ECD helicity rule has been proposed for the absolute
configuration of 5-substituted 2(5H)-furanones [11]. This rule uses
0
correlations from H-1 to C-4 positioned the sugar moiety at C-4.
Thus, the planar structure of 2 was established as a demethylated
derivative of 1.
the ECD signs of n-p* and p-p* transitions of a,b-unsaturated lac-
Kim, Jong Won
