Diastereoselective synthesis of pyrrolidines via 1,3-dipolar cycloaddition of a chiral azomethine ylide

Article abstract of DOI:10.1016/j.tetlet.2009.10.030

1,3-Dipolar cycloaddition of d-glucose-derived azomethine ylides for the synthesis of chiral pyrrolidines accompanied an unexpected 1,2-elimination in the furanose moiety of the products. The C3′ alkoxy/hydroxy group of the furanose moiety was invariably eliminated under the reaction conditions. Also, in contrast to the previous reports, moderate to good exo-diastereoselectivity was observed in the reaction products.

Full text of DOI:10.1016/j.tetlet.2009.10.030

Tetrahedron Letters 50 (2009) 7175–7179
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Tetrahedron Letters
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Diastereoselective synthesis of pyrrolidines via 1,3-dipolar cycloaddition of
a chiral azomethine ylide
*
K. Karthikeyan, R. Senthil Kumar, D. Muralidharan, P. T. Perumal
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
a r t i c l e i n f o
a b s t r a c t
Article history:
1,3-Dipolar cycloaddition of D-glucose-derived azomethine ylides for the synthesis of chiral pyrrolidines
accompanied an unexpected 1,2-elimination in the furanose moiety of the products. The C30 alkoxy/
hydroxy group of the furanose moiety was invariably eliminated under the reaction conditions. Also,
in contrast to the previous reports, moderate to good exo-diastereoselectivity was observed in the reac-
tion products.
Received 21 September 2009
Revised 2 October 2009
Accepted 7 October 2009
Available online 14 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
O
1. Introduction
Bn
O
OHC
RO
O
N
H
+
+
N
Ph
O
1,3-Dipolar cycloaddition is one of the simplest approaches for
the construction of five-membered heterocyclic ring systems.1 The
high regio- and stereoselectivity observed in the 1,3-dipolar cyclo-
addition enables it to be one of the powerful tools for synthesis of
various chiral natural products.2 Dipolar cycloaddition of azome-
thine ylide has been used in many instances for the diastereoselec-
tive synthesis of various pyrrolidine-based alkaloids that find
applications as chiral building blocks and chiral catalyst in organic
synthesis.3–7 Highly substituted pyrrolidines are well known for
their glucosidase inhibitory activity in addition to potent antiviral,
antibacterial, antidiabetic and anticancer activities.8
The major role played by carbohydrates in various biological
processes is evident from the recent advances made in glycobiol-
ogy.9 Since carbohydrates occur as constituents of various glyco-
proteins and glycolipids, the development of carbohydrate-based
drugs will be of much use in the treatment of various diseases10
such as obesity and diabetes.
O
O
O
2a
3a
1a-d
R
1a Bn
1b Et
Toluene
reflux
1c CH2COOMe
1d H
Bn
Bn
O
O
O
O
O
N
O
N
O
O
O
O
O
OR
O
O
O
N
N
Ph
Ph
4a-d
5a-8a
2. Results and discussion
Scheme 1.
In continuation of our interest in the 1,3-dipolar cycloaddition
reactions for the synthesis of biologically active heterocycles,11
we intended to explore the chiral version of the same. To this
end, we synthesized various 3-O-alkyl-1,2-O-isopropylidene-xylo-
To evaluate the feasibility of our approach, we refluxed a solu-
tion of the aldehyde 1a, glycine ester 2a and N-phenyl maleimide
3a in toluene (Scheme 1). 1H NMR spectrum of the crude reaction
mixture revealed the presence of four diastereoisomers in the ratio
of 58:13:15:14. Flash column chromatography of the mixture re-
sulted in the isolation of three components of which one was found
to be an inseparable mixture and the other two components being
the pure diastereomers.
pentadialdoses starting from D
-glucose.12 Our synthetic strategy
was to trap the in situ generated azomethine ylides obtained from
the above aldehyde and various N-benzyl secondary amines13 with
maleimides to synthesize the chiral pyrrolidine.
However, NMR and mass spectral data of the product did not
match with the expected structure 4a. The mass spectra of the
products revealed a peak at m/z = 519 instead of the expected
m/z = 626, the difference corresponds to the loss of molecule of
* Corresponding author. Tel.: +91 44 24911329; fax: +91 44 24911539.
E-mail address: ptperumal@gmail.com (P.T. Perumal).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.030

7176
K. Karthikeyan et al. / Tetrahedron Letters 50 (2009) 7175–7179
benzyl alcohol. This was further confirmed from 1H NMR spectrum,
which revealed the absence of signal due to benzylic protons
(CH2–Ph). Also, in the furanose moiety only three protons were ob-
served and their chemical shift positions were deshielded. Based
on the above facts, the structure of the compound was assigned
to be olefins 5a–8a. Quite interestingly, our strategy furnished
the 1,3-dipolar cycloaddition products with an unusual exo-
diastereoselectivity.14,15 It is worth mentioning that when the 3-O-
benzyl group in xylopentadialdose was replaced by ethyl or
carbmethoxy methylene group a similar elimination was observed.
Elimination occurred even with an unprotected hydroxyl group
present at C30 resulting in the same olefins 5a–8a (Scheme 1,
Table 1).
8a–f were obtained as pure diastereomers whereas 6a–f and 7a–
f were obtained as an inseparable diastereomeric mixture. How-
ever, with the ylide derived from ester 2b (R00 = Bn) all the four
diastereomers were separated by flash column chromatography.
The overall yield ranged from 67% to 80% with 5a–h as the major
product. When maleimide was replaced by nitrostyrene the
cycloaddition products were obtained as an inseparable mixture.
The systematic structural analysis of the four isomers to
elucidate the exact regio- and stereochemistry was performed
using 1H, 13C and various 2D NMR spectroscopic techniques. The
assignment of signals and the regio- and stereochemistry for a
representative case (5g–8g) is discussed here.16
Having ended up with the elimination product in all the above
cases, we next treated the ylide obtained from glycine esters 2a, 2b
with various maleimides 3a–f (Scheme 2, Table 2). With the ylide
derived from glycine ester 2a (R00 = Et) the pyrrolidines 5a–f and
2.1. Structural assignment of diastereoisomers (5g)
In the 1H–1H COSY spectrum of 5g, the proton at 5.87 ppm (ano-
meric proton, H-10) showed correlation with the proton at
Table 1
Cycloaddition of aldehydes 1a–d with glycine ester 2a and N-phenyl maleimide 3a
Entry
R
Adducts
Products
exo/endo
Time (h)
Yieldb (%)
% of diastereoisomersa
5a
6a
7a
8a
1
2
3
4
Bn
Et
5a–8a
5a–8a
5a–8a
5a–8a
58
57
55
56
13
14
14
14
15
15
16
16
14
14
15
14
73:27
72:28
71:29
72:28
3
3
4.5
6
75
70
68
45
CH2COOMe
H
a
Determined by 1H NMR spectrum of the crude product.
Isolated yield after flash column chromatography.
b
Bn
O
N
R''
Bn
N
R''
O
O
Bn
R''
H
H
H
O
O
H
H
O
O
+
N
O
O
O
2a-b
O
O
H
H
H
H
+
O
O
N
O
O
O
N
OHC
R'
R'
Toluene
reflux
O
exo 5a-h
endo 6a-h
BnO
O
R''
Bn
R''
Bn
O
1a
O
H
O
O
H
H
H
N
O
N
+
O
+
O
O
O
O
H
H
H
H
O
O
N
O
O
O
O
N
N
R'
R'
R'
3a-f
endo 8a-h
exo 7a-h
Scheme 2.
Table 2
Cycloaddition of aldehyde 1a with glycine ester 2a–b and N-substituted maleimide 3a–f
Entry
R0
R00
Adducts
Products
% of diastereoisomera
Time (h)
exo/endo
Overall yieldb (%)
5
6
7
8
1
2
3
4
5
6
7
8
Ph
p-MePh
Bn
p-BrPh
Me
H
Et
Et
Et
Et
Et
Et
Bn
Bn
5a–8a
5b–8b
5c–8c
5d–8d
5e–8e
5f–8f
58
59
66
54
65
59
54
56
13
11
9
14
10
13
15
12
15
16
16
18
13
15
16
16
14
14
9
14
12
13
15
16
3.0
3.5
2.5
4.5
2.5
4.0
3.5
3.5
73:27
75:25
82:18
72:28
78:22
74:26
70:30
72:28
75
76
80
71
79
67
72
70
Ph
p-MePh
5g–8g
5h–8h
a
Determined by 1H NMR spectrum of the crude product.
Isolated yield after flash column chromatography.
b

K. Karthikeyan et al. / Tetrahedron Letters 50 (2009) 7175–7179
7177
5.19 ppm. Also the proton at 5.19 ppm showed correlation with the
3.0%
11.2%
proton at 5.47 ppm in addition to that with the proton at 5.87 ppm.
Hence we assigned the signals at 5.19 ppm to H-20 and 5.47 ppm to
H-30. In the HMBC spectrum, the above three protons showed con-
tour with carbon at 155.0 ppm and therefore this carbon should be
C40 (Fig. 1). The doublet at d 4.47 ppm (J = 9.2 Hz) and triplet at
3.59 ppm (J = 8.4 Hz) exhibited HMBC with carbon at 155.0 ppm
corresponding to C40 and hence the protons were assigned as H-3
and H-3a, respectively. The singlet at d 4.16 ppm and doublet at
3.41 ppm (J = 8.4 Hz) exhibited HMBC contour with carbon at
168.8 ppm corresponding to the ester carbonyl carbon and the pro-
tons were assigned as H-1 and H-6a, respectively. Compound 7g
exhibited NMR patterns similar to 5g (Fig. 2).
Bn
Bn
Bn
N
21.0%
Bn
N
18.7%
O
O
O
O
H
H
H
H
O
O
O
O
5.6%
6.3%
O
O
H
H
H
H
H
H
O
O
O
O
N
N
Ph
Ph
5g
7g
Figure 3. 1-D NOE enhancement of compounds 5g and 7g.
nal of H-6a (5.6%) and no enhancement of H-3 proton. Irradiation
of H-3 effected enhancement of the signals of H-3a (21.0%), H-30
(11.2%) and no enhancement of H-1 proton. These facts show that
the proton H-3 is cis to H-3a and H-1 is trans to H-6a. Also the pro-
tons H-1 and H-3 have anti-relationship (Fig. 3). The structure of 5c
was further confirmed by single crystal X-ray diffraction studies
(Fig. 4).17 The same discussion is applicable to compound 7g
(Fig. 3).
2.2. Stereochemical elucidation of the exo diastereoisomers
(5g)
The stereochemistry of the diastereoisomer 5g was confirmed
as exo from the coupling constant values of H-3, H-3a, H-6a and
H-1 protons and NOE experiments. In compound 5g, the coupling
constant between H-3 and H-3a was 9.2 Hz and there was no cou-
pling between H-6a and H-1. This shows that the proton H-3 is cis
to H-3a and H-1 is trans to H-6a. In one dimensional NOE measure-
ments selective irradiation of H-1 effected enhancement of the sig-
2.3. Structural assignment of diastereoisomers (8g)
In the 1H NMR spectrum of compound 8g, the doublet at d
4.25 ppm (J = 2.3 Hz) and doublet of doublet at 3.45 ppm (J = 8.4,
1.6 Hz) exhibited HMBC with carbon at 157.0 ppm corresponding
to C40 and hence the protons were assigned as H-3 and H-3a,
Bn
O
O
168.8 ppm
H
Bn
2
N
H
3.41 (d, J = 8.4 Hz)
1
6a
O
155.0 ppm
H
3
6
O
4'
3a
H
5.87 (d, J = 5.4 Hz)
1'
N
H
5
Ph
O
4
2'
3'
O
H
O
H
5.19 (dd, J = 5.4, 2.3 Hz)
5g
Figure 4. ORTEP diagram of compound 5c.
Figure 1. Selective HMBC of compound 5g.
Bn
Bn
O
O
O
O
H
170.6 ppm
H
170.3 ppm
Bn
Bn
2
2
H
3.43 (d, J = 8.4 Hz)
H
1
3.86 (t, J = 8.4 Hz)
N
6a
1
N
O
6a
O
H
159.1 ppm
3
157.0 ppm
H
3
6
O
6
4'
3a
O
4'
3a
H
6.02 (d, J = 5.4 Hz)
1'
H
N
5
6.07 (d, J = 5.4 Hz)
1'
N
H
H
Ph
O
5
4
Ph
O
2'
4
2'
3'
O
3'
O
H
H
O
H
O
H
5.15 (dd, J = 5.4, 2.3 Hz)
5.31 (dd, J = 5.4, 2.3 Hz)
7g
8g
Figure 5. Selective HMBC of compound 8g.
Figure 2. Selective HMBC of compound 7g.

7178
K. Karthikeyan et al. / Tetrahedron Letters 50 (2009) 7175–7179
2.4. Stereochemical elucidation of the endo diastereoisomers
(8g)
Bn
O
For compound 8g, the coupling constant between H-3 and H-3a
O
was 2.3 Hz and H-1 and H-6a was 9.2 Hz. In 1-D NOE measure-
ments selective irradiation of H-1 effected enhancement of the sig-
nal of H-6a (16.3%). Irradiation of H-3 effected enhancement of the
signals of H-3a (6.3%) and H-30 (8.9%). From the coupling constants
and 1D NOE data, the proton H-1 was found to be cis to H-6a and
H-3 trans to H-3a ( Fig. 7). The structure of 8c was confirmed
through single crystal X-ray diffraction studies (Fig. 8).18 The same
discussion is applicable to compound 6g (Fig. 7).
H
170.3 ppm
Bn
2
H
3.82 (t, J = 8.4 Hz)
1
N
6a
O
H
158.4 ppm
O
3
6
4'
3a
H
6.07 (d, J = 5.4 Hz)
1'
N
H
5
Ph
O
4
2'
3'
O
H
In summary, an efficient synthesis of chiral pyrrolidines was
accomplished using 1,3-dipolar cycloaddition of a D-glucose-de-
O
H
5.24 (dd, J = 5.4, 2.3 Hz)
rived azomethine ylide as the dipole. The unusual 1,2-elimination
observed in the furanose moiety of the pyrrolidine resulted in the
installation of enol ether functionality which is amenable to vari-
ous synthetic manipulations. Also noteworthy is the fact that the
reaction showed an exo-diastereoselectivity against the endo-dia-
stereoselectivity observed in other similar reported reactions.
These chiral carbohydrate tethered pyrrolidines on account of the
presence of the masked aldehyde in the vicinity of potential amino
group (N-Bn) would be the ideal precursors for the synthesis of
various indolizidine type alkaloids.
6g
Figure 6. Selective HMBC of compound 6g.
respectively. The doublet at d 4.37 ppm (J = 9.2 Hz) and triplet at
3.86 ppm (J = 8.4 Hz) exhibited HMBC contour with carbon at
170.3 ppm corresponding to the ester carbonyl carbon and the pro-
tons were assigned as H-1 and H-6a, respectively. (Fig. 5) Com-
pound 6g exhibited NMR patterns similar to 8g. (Fig. 6)
Acknowledgement
One of the authors, K.K., thanks the Council of Scientific and
Industrial Research, New Delhi, India, for the research fellowship.
Supplementary data
8.9%
8.1%
6.6%
6.3%
Bn
N
Bn
Bn
Bn
N
O
O
O
O
H
H
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.030.
H
H
O
O
O
O
18.6%
16.3%
O
O
H
H
H
H
H
H
References and notes
O
O
O
O
N
N
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6g
8g
Figure 7. 1-D NOE enhancement of compounds 6g and 8g.
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Figure 8. ORTEP diagram of compound 8c.

K. Karthikeyan et al. / Tetrahedron Letters 50 (2009) 7175–7179
7179
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133.2, 135.1, 155.0, 168.8, 172.9, 173.2; ESI-MS (LCQ) m/z = 581 M++1. Anal.
Calcd for C34H32N2O7 (580.22): C, 70.33; H, 5.56; N, 4.82. Found: C, 70.50; H,
5.52; N, 4.76.
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benzylamine with ethyl or benzyl bromoacetate in the presence of
diisopropylethylamine in dichloromethane under reflux.
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Tetrahedron 2007, 63, 6587.
endo 6g: Colourless solid; mp 60–62 °C; Rf = 0.56 (50% ethylacetate/petroleum
ether); IR (cmꢀ1): 2984, 1719, 1659, 1495, 1378, 1196, 1040; ½a 3D1
ꢁ
+152.9 (0.42,
CHCl3); 1H NMR (500 MHz, CDCl3): d 1.43 (s, 3H), 1.60 (s, 3H), 3.45 (dd, 1H,
J = 8.4, 1.6 Hz, H-3a), 3.53 (d, 1H, J = 13.0 Hz, –NCHH), 3.82 (t, 1H, J = 8.4 Hz, H-
6a), 3.91 (d, 1H, J = 13.8 Hz, –NCHH), 4.23 (d, 1H, J = 1.5 Hz, H-3), 4.37 (d, 1H,
J = 8.4 Hz, H-1), 5.11 (s, 2H), 5.17 (d, 1H, J = 2.3 Hz, H-30), 5.24 (dd, 1H, J = 5.4,
2.3 Hz, H-20), 6.07 (d, 1H, J = 5.4 Hz, H-10), 7.21–7.25 (m, 7H, Ar–H), 7.32–7.34
(m, 4H, Ar–H), 7.39 (t, 2H, J = 6.9 Hz, Ar–H), 7.45 (d, 2H, J = 7.7 Hz, Ar–H); 13C
NMR (100 MHz, CDCl3): d 27.5, 28.4, 47.3, 48.3, 51.7, 59.3, 66.1, 67.5, 82.9,
103.5, 106.7, 112.4, 126.6, 127.4, 128.4, 128.5, 128.6, 128.7, 128.9, 129.1, 129.2,
131.9, 135.1, 137.3, 158.4, 170.3, 175.2, 175.9; ESI-MS (LCQ) m/z = 581 M++1.
Anal. Calcd for C34H32N2O7 (580.22): C, 70.33; H, 5.56; N, 4.82. Found: C, 70.52;
H, 5.59; N, 4.88.
exo 7g: Less amount of endo 8g was present; viscous liquid; Rf = 0.59 (50%
ethylacetate/petroleum ether); IR (cmꢀ1): 2989, 1718, 1660, 1497, 1375, 1196,
1045; ½a 2D6
ꢁ
ꢀ57.5 (0.64, CHCl3); 1H NMR (500 MHz, CDCl3): d 1.39 (s, 3H), 1.48
(s, 3H), 3.43 (d, 1H, J = 8.4 Hz, CH-6a), 3.52 (d, 1H, J = 13.8 Hz, –NCHH), 3.77 (t,
1H, J = 9.2 Hz, H-3a), 4.02 (d, 1H, J = 12.3 Hz, –NCHH), 4.23 (s, 1H, H-1), 4.41 (d,
1H, J = 9.2 Hz H-3), 5.09 (d, 1H, J = 12.3 Hz), 5.15 (dd, 1H, J = 5.4, 2.3 Hz, H-20),
5.25 (d, 1H, J = 12.3 Hz), 5.33 (d, 1H, J = 2.3 Hz, H-30), 6.02 (d, 1H, J = 5.4 Hz, H-
10), 7.07–7.08(m, 2H, Ar–H), 7.21–7.24 (m, 3H, Ar–H), 7.29 (d, 2H, J = 7.7 Hz,
Ar–H), 7.34–7.41(m, 6H, Ar–H), 7.47 (t, 2H, J = 7.7 Hz, Ar–H); 13C NMR
(100 MHz, CDCl3): d 27.6, 27.8, 47.7, 48.5, 52.1, 61.4, 63.3, 66.8, 82.7, 100.7,
106.6, 112.7, 126.4, 127.8, 128.3, 128.5, 128.6, 128.7, 128.8, 129.1, 129.2, 131.9,
135.1, 137.1, 159.1, 170.6, 174.0, 175.1; ESI-MS (LCQ) m/z = 581 M++1. Anal.
Calcd for C34H32N2O7 (580.22): C, 70.33; H, 5.56; N, 4.82. Found: C, 70.42; H,
5.63; N, 4.72.
15. For metalcatalyzed exo-selective 1,3-dipolar cycloaddition see: (a) Peddibhotla,
S.; Tepe, J. J. J. Am. Chem. Soc. 2004, 126, 12776; (b) Oderaotoshi, Y.; Cheng, W.;
Fujitomi, S.; Kasano, Y.; Ninakata, S.; Komatsu, M. Org. Lett. 2003, 5, 5043; (c)
Ayerbe, M.; Arrieta, A.; Cossio, F. P. J. Org. Chem. 1998, 63, 1795.
16. Experimental procedure for compounds 5–8: A mixture of 3-O-benzyl-1,2-O-
isopropylidene-xylopentadialdose 1a (1.08 mmol), N-benzyl glycine ethyl or
endo 8g: Colourless solid; mp 138–140 °C; Rf = 0.65 (50% ethylacetate/
petroleum ether); IR (cmꢀ1): 2984, 1718, 1662, 1495, 1385, 1190, 1044;
½ ꢁ
a 3D0 +93.2 (0.60, CHCl3); 1H NMR (500 MHz, CDCl3): d 1.43 (s, 6H), 3.41
(d, 1H, J = 13.0 Hz, –NCHH), 3.45 (dd, 1H, J = 8.5, 1.6 Hz, H-3a), 3.84 (d, 1H,
J = 13.0 Hz, –NCHH), 3.86 (t, 1H, J = 8.4 Hz, H-6a), 4.25 (d, 1H, J = 2.3 Hz, H-3),
4.37 (d, 1H, J = 9.2 Hz, H-1), 5.09–5.16 (m, 3H), 5.31 (dd, 1H, J = 5.4, 2.3 Hz, H-
20), 6.07 (d, 1H, J = 5.4 Hz, H-10), 7.22–7.26(m, 7H, Ar–H), 7.32–7.37 (m, 5H,
Ar–H), 7.41 (d, 1H, J = 6.9 Hz, Ar–H), 7.45 (t, 2H, J = 7.6 Hz, Ar–H); 13C NMR
(100 MHz, CDCl3): d 27.8, 28.5, 29.7, 47.4, 51.9, 59.5, 66.3, 67.5, 83.1, 103.9,
106.2, 112.3, 126.7, 127.5, 128.3, 128.4, 128.5, 128.6, 128.8, 129.0, 129.2,
131.8, 135.1, 137.3, 157.0, 170.3, 175.3, 175.9; ESI-MS (LCQ) m/z = 581 M++1.
Anal. Calcd for C34H32N2O7 (580.22): C, 70.33; H, 5.56; N, 4.82. Found: C,
70.22; H, 5.52; N, 4.87.
benzyl ester
2 (1.29 mmol) and N-aryl/alkyl maleimide 3 (1.29 mmol) in
toluene (15 ml) was refluxed for 3 h. After completion of the reaction, the
solvent was evaporated under reduced pressure and the products 5–8 were
separated by flash column chromatography using silica gel (230–400 mesh)
with ethyl acetate: petroleum ether as an eluent.
2-Benzyl-3-(2,2-dimethyl-3a,6a-dihydro-furo[2,3-d][1,3]dioxol-5-yl)-4,6-dioxo-5-
phenyl-octahydro-pyrrolo[3,4-c]pyrrole-1-carboxylic acid benzyl ester (5g, 6g, 7g,
8g): Yield: 0.451 g (72%):exo 5g: Colourless solid; mp 63–65 °C; Rf = 0.54 (50%
ethylacetate/petroleum ether); IR (cmꢀ1): 2981, 1717, 1657, 1498, 1384, 1192,
17. Crystallographic data for the structure 5c in this Letter have been deposited
with the Cambridge Crystallographic Data centre as supplemental Publication
No. CCDC-689250. Copies of the data can be obtained, free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 01223
336033 or email: deposit@ccdc.cam.ac.uk).
18. Crystallographic data for the structure 8c in this Letter have been deposited
with the Cambridge Crystallographic Data centre as supplemental Publication
No. CCDC-699267. Copies of the data can be obtained, free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 01223
336033 or email: deposit@ccdc.cam.ac.uk).
1045; ½a 3D0
ꢁ
ꢀ37.9 (1.18, CHCl3); 1H NMR (500 MHz, CDCl3): d 1.38 (s, 3H), 1.39
(s, 3H), 3.41 (d, 1H, J = 8.4 Hz, H-6a), 3.48 (d, 1H, J = 13.0 Hz, ꢀNCHH), 3.59 (t,
1H, J = 8.4 Hz, H-3a), 3.94 (d, 1H, J = 13.0 Hz, ꢀNCHH), 4.16 (s, 1H, H-1), 4.47 (d,
1H, J = 9.2 Hz, H-3), 5.10 (d, 1H, J = 11.5 Hz), 5.19 (dd, 1H, J = 5.4, 2.3 Hz, H-20),
5.25 (d, 1H, J = 12.3 Hz), 5.47 (d, 1H, J = 2.3 Hz, H-30), 5.87 (d, 1H, J = 5.4 Hz, H-
10), 7.12–7.14(m, 2H, Ar–H), 7.21–7.22 (m, 3H, Ar–H), 7.32 (d, 2H, J = 7.7 Hz,
Ar–H), 7.35–7.43(m, 6H, Ar–H), 7.50 (t, 2H, J = 7.7 Hz, Ar–H); 13C NMR
(100 MHz, CDCl3): d 25.6, 26.0, 45.4, 46.6, 49.6, 59.2, 60.7, 64.8, 80.8, 102.7,