A stereocontrolled access to α-C-(1→3)-linked disaccharides containing 2-deoxyhexopyranoses

Article abstract of DOI:10.1055/s-2003-39288

A protected α-D-glucopyranosylacetaldehyde was convened by Wittig reaction with (thiazol-2-yl)carbonylmethylenetriphenyl phosphorane into the corresponding substituted 1-oxa-1,3-butadiene which by hetero-Diels-Alder reaction with ethyl vinyl ether afforde

Full text of DOI:10.1055/s-2003-39288

LETTER
963
A Stereocontrolled Access to a-C-(1→3)-Linked Disaccharides Containing
2-Deoxyhexopyranoses
A
a
S
tereocontr
o
e
lle
d
A
cces
t
s
to
a
-
C
r
-(13)-linked
D
Š
isaccharides těpánek,a Ladislav Kniežo,*a Hana Dvořáková,b Pavel Vojtíšekc
Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
Fax +420(2)33339990; E-mail: ladislav.kniezo@vscht.cz
b
c
NMR Laboratory, Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
Department of Inorganic Chemistry, Charles University, 128 40 Prague 2, Czech Republic
Received 27 February 2003
In our previous studies we described a method by which a
formyl group can be converted to a new dideoxyhexo-
pyranose and using this approach, we prepared com-
pounds in which two monosaccharides were linked either
Abstract: A protected a-D-glucopyranosylacetaldehyde was con-
verted by Wittig reaction with (thiazol-2-yl)carbonylmethylene-
triphenyl phosphorane into the corresponding substituted 1-oxa-
1,3-butadiene which by hetero-Diels–Alder reaction with ethyl
vinyl ether afforded a mixture of two diastereoisomeric dihydropy- directly by a C-C bond7 or by a -CH2-bridge.8 In the
ran derivatives. These were separated by chromatography and the
thiazol ring was transformed into an aldehyde group. Subsequent
present communication we publish a short and simple
synthesis of a new type of a-C-(1Æ3)-disaccharide using
hydroboration afforded a-C-(1→3)-linked disaccharides containing
the same methodology. Some types of C-(1Æ3)-disaccha-
2-deoxyhexopyranoses of D- or L-configuration.
rides are already known in which two monosaccharides
are linked by a -CH2-,4 -CH(OH)-5 or -CO-6 bridge. Re-
Key words: C-disaccharides, C-glycosides, hetero-Diels–Alder re-
action, oxabutadienes, Wittig reaction
cently, the epimeric pair a-C-(1Æ3)-mannopyranoside of
N-acetylgalactosamine and a-C-(1Æ3)-mannopyranoside
of N-acetyltalosamine has been prepared and the former
Formal replacement of the glycosidic oxygen atom by a
isomer showed inhibitory effects toward glycosidases and
human a-1,3-fucosyltransferase.9
methylene group in disaccharides leads to a group of com-
pounds denoted trivially as C-disaccharides. Although
this change can influence the conformational arrangement
We used protected a-D-glucopyranosylacetaldehydes 1 or
2 as starting compounds. These aldehydes are accessible,
about the original C-O-C bonds,1 it is assumed that C-di-
even in multigram amounts, by ozonolysis of the corre-
saccharides mimic well the structures of the natural disac-
sponding peracetylated10 or perbenzylated11 propenyl de-
charides but – unlike them – they resist acidic as well as
rivatives. Heating a mixture of substituted acetaldehyde 1
enzyme hydrolysis. Therefore, C-disaccharides are poten-
tial inhibitors of glycosidases or glycosyltransferases.
Since these enzymes play a crucial role in the biosynthesis
and stabilized ylide 312 in chloroform afforded trans-oxa-
diene 413 which was isolated by column chromatography
in 80% yield (Scheme 1). As in the previous cases,7,8
of cell-surface oligosaccharides that are important for in-
Eu(fod)3-catalyzed cycloaddition of oxadiene 4 to ethyl
tercellular communication, we can expect that some C-
vinyl ether led to a mixture of two endo-cycloadducts 6
disaccharides could find use as compounds with therapeu-
and 7. Similarly to the synthesis of the branched-chain
tic effects.2
sugars,8 we observed no chiral induction by the monosac-
For these reasons, there is an increased interest in the
search for new synthetic pathways leading to C-disaccha-
charide moiety in the cycloaddition reaction, both endo-
cycloadducts 6 and 7 being formed in the ratio 1:1 (as de-
rides and in the study of their properties.2–6 Because of the
great structural variety of disaccharides, where e.g. one
hexopyranose can be attached by an a- or b-anomeric
bond to five different positions (i.e. positions 1, 2, 3, 4 or
6) of the second hexopyranose, the existing methods of
preparation of C-disaccharides are usually multi-step syn-
theses, enabling the preparation of only one particular
type of C-disaccharide. Therefore, a search for further
simple syntheses of various types of C-disaccharides is
desirable, particularly for those which could afford the fi-
nal compounds in sufficient quantities for testing their
properties.
termined by 1H NMR spectroscopy and HPLC).14 Unfor-
tunately, the cycloadducts 6 and 7 were inseparable by
preparative chromatography on silica gel. Therefore, we
repeated the reaction, starting from benzyl-protected ace-
taldehyde 2.
Analogously to 1, the Wittig reaction of 2 afforded oxadi-
ene 5 and subsequent cycloaddition under the same condi-
tions as in the preceding case gave 1:1 mixture of two
cycloadducts 8 and 9.15 We confirmed the structural iden-
tity of the pair of products 6 and 7 and the pair 8 and 9 by
deacetylation of the mixture of cycloadducts 6 and 7 and
subsequent benzylation which gave a mixture of cyclo-
adducts 8 and 9. Contrary to the pair 6 and 7, the mixture
of 8 and 9 was well separable on silica gel and pure com-
Synlett 2003, No. 7, Print: 02 06 2003.
Art Id.1437-2096,E;2003,0,MM,0963,0966,ftx,en;D05103ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

964
P. Štěpánek et al.
LETTER
Scheme 1 Reagents and conditions: i. ethyl vinyl ether, Eu(fod)3 (7.5 mol%), CH2Cl2, r.t., 6 h; ii. a) MeOTf, MeCN, r.t., 15 min, b) NaBH4,
MeOH, r.t., 15 min, c) AgNO3, MeCN/H2O, r.t., 20 min; iii. a) Me2S·BH3, THF, r.t., 18 h, b) NaOH, H2O2, r.t., 40 min; iv. H2/Pd-C, MeOH,
r.t., 16 h v. Ac2O, pyridine, DMAP, r.t., 4 h.
pounds were obtained by flash chromatography. Mass and less hindered side of the dihydropyran double bond and
NMR spectra confirmed that compounds 8 and 9 represent afforded benzylated products 12 and 15.17 Removal of the
a pair of diastereoisomers differing only in configuration benzyl protecting groups by hydrogenation gave ethyl
on the dihydropyran ring.15 Moreover, the presence of glycosides of a-C-(1Æ3)-disaccharides 13 and 16, which
NOE between the protons H-1a and H-3a in the individual were characterized as peracetyl derivatives 14 and 17.18
diastereoisomers 8 and 9 confirmed the cis-configuration Whereas ethyl glycoside of C-disaccharide 17 with L-con-
of substituents on the dihydropyran ring in both com- figuration in the new deoxyhexopyranose was obtained as
pounds.
a crystalline compound of mp 145–147 °C, its diastereo-
isomer 14 was contaminated with minor impurities (up to
20%), even after chromatography on silica gel. As
shown by NMR spectra, in both the new deoxypyranoses
14 and 17 all substituents are equatorial18 (for 14: J =
H-1a/H-2aax = 9.4 Hz; J = H-3a/H-4a = 9.0 Hz; J = H-4a/
H-5a = 10.0 Hz; for 17: J = H-1a/H-2aax = 8.1 Hz; J =
H-3a/H-4a = J = H-4a/H-5a = 9.9 Hz).
In the two subsequent steps, both the individual cycload-
ducts 8 and 9 were converted into compounds 12 and 15.
In the first step, the thiazole substituent was in the known
way16 transformed to a formyl group, giving rise to little
stable aldehydes 10 and 11. Their hydroboration with an
excess of (CH3)2S·BH3, with simultaneous reduction of
the formyl group, proceeded stereoselectively from the
Synlett 2003, No. 7, 963–966 ISSN 1234-567-89 © Thieme Stuttgart · New York

LETTER
A Stereocontrolled Access to a-C-(1→3)-Linked Disaccharides
965
Schmidt, R. R. Chem. Eur. J. 1996, 2, 502. (d) Witczak, Z.
J.; Chabra, R.; Chojnacki, J. Tetrahedron Lett. 1997, 38,
2215. (e) Rubinstenn, G.; Esnault, J.; Mallet, J.-M.; Sinaÿ, P.
Tetrahedron: Asymmetry 1997, 8, 1327. (f) Angelaud, R.;
Landais, Y.; Parra-Rapado, L. Tetrahedron Lett. 1997, 38,
8845. (g) Bornaghi, L.; Utille, J. P.; Mekai, E. D.; Mallet,
J.-M.; Sinaÿ, P.; Driguez, H. Carbohydr. Res. 1997, 305,
561. (h) Dondoni, A.; Zuurmond, H.; Boscarato, A. J. Org.
Chem. 1997, 62, 8114. (i) Sutherlin, D. P.; Armstrong, R.
W. J. Org. Chem. 1997, 62, 5267. (j) Lubineau, A.; Grand,
E.; Scherrmann, M.-C. Carbohydr. Res. 1997, 297, 169.
(k) Rubinstenn, G.; Mallet, J.-M.; Sinaÿ, P. Tetrahedron
Lett. 1998, 39, 3697. (l) Du, Y.; Polat, T.; Linhardt, R. J.
Tetrahedron Lett. 1998, 39, 5007. (m)Dondoni, A.;Kleban,
M.; Zuurmond, H.; Marra, A. Tetrahedron Lett. 1998, 39,
7991. (n) Mekai, E. D.; Rubinstenn, G.; Mallet, J.-M.; Sinaÿ,
P. Synlett. 1998, 831. (o) Sazaki, M.; Fuwa, H.; Inoue, M.;
Tachibana, K. Tetrahedron Lett. 1998, 39, 9027. (p) Patro,
B.; Schmidt, R. R. Synthesis 1998, 1731. (q) Jarreton, O.;
Skrydstrup, T.; Espinosa, J.-F.; Jiménez-Barbero, J.; Beau,
J.-M. Chem.-Eur. J. 1999, 5, 430. (r) Pham-Huu, D.-P.;
Petrušová, M.; Bemiller, J. N.; Petruš, L. Tetrahedron Lett.
1999, 40, 3053. (s) Postema, M. H. D.; Calimente, D.
Tetrahedron Lett. 1999, 40, 4755. (t) Roy, R.; Dominique,
R.; Das, S. K. J. Org. Chem. 1999, 64, 5408.
The L-configuration of the new deoxyhexopyranose in the
crystalline ethyl glycoside 17 has been unequivocally
confirmed by X-ray crystallographic analysis (see
Figure 1),19 which leaves the D-configuration for the new
deoxyhexopyranose in ethyl glycoside 14.
In summary, we have shown that the described method
represent a direct and rapid approach to two diastereoiso-
meric a-C-(1Æ3)-disaccharides 13 and 16 in which D-glu-
cose is linked by methylene bridge with 2-deoxy-
hexopyranose in the D- and in the L-configuration, respec-
tively. Now, we are trying to use as starting compounds
other aldehydes derived from monosaccharides (e.g. of
galacto or manno configuration) in order to obtain a
broader series of a-C-(1Æ3)-disaccharides for biological
activity screening.
(4) (a) Dyer, U. C.; Kishi, Y. J. Org. Chem. 1998, 53, 3383.
(b) Wang, Y.; Goekjian, P. G.; Ryckman, D. M.; Kishi, Y. J.
Org. Chem. 1998, 53, 4151. (c) Bimbala, R. M.; Vogel, P.
Tetrahedron Lett. 1991, 32, 1429. (d) Bimbala, R. M.;
Vogel, P. J. Org. Chem. 1992, 57, 2076.
(5) (a) Schmidt, R. R.; Beyerbach, A. Liebigs Ann. Chem. 1992,
983. (b) Zhu, Y.-H.; Vogel, P. Tetrahedron Lett. 1998, 39,
31. (c) Gerber, P.; Vogel, P. Tetrahedron Lett. 1999, 40,
3165. (d) Zhu, Y.-H.; Demange, R.; Vogel, P. Tetrahedron:
Asymmetry 2000, 11, 263.
(6) Dawson, I. M.; Johnson, T.; Paton, R. M.; Rennie, A. C. J.
Chem. Soc., Chem. Commun. 1988, 1339.
(7) (a) Dondoni, A.; Kniežo, L.; Martinková, M. J. Chem. Soc.,
Chem. Commun. 1994, 1963. (b) Dondoni, A.; Kniežo, L.;
Martinková, M.; Imrich, J. Chem.-Eur. J. 1997, 3, 424.
(8) Kniežo, L.; Buděšínský, M.; Vojtíšek, P.; Martinková, M.
Enantiomer 1999, 4, 351.
Figure 1
(9) (a) Pasquarello, C.; Demange, R.; Vogel, P. Bioorg. Med.
Chem. Lett. 1999, 9, 793. (b) Pasquarello, C.; Picasso, S.;
Demange, R.; Malissard, M.; Berger, E. C.; Vogel, P. J. Org.
Chem. 2000, 65, 4251.
(10) Abdel-Rahman, A. A.-H.; El Ashry, E.-S. H.; Schmidt, R. R.
Carbohydr. Res. 1999, 315, 106.
Acknowledgement
This study was financially supported by Ministry of Education,
Youth and Sport of the Czech Republic (Grant No 22330006).
(11) Brenna, E.; Fuganti, C.; Grasseli, P.; Serra, S.; Zambotti, S.
Chem.–Eur. J. 2002, 8, 1872.
(12) Dondoni, A.; Marra, A.; Merino, P. J. Am. Chem. Soc. 1994,
116, 3224.
References
(1) Mikros, E.; Labrinidis, G.; Pérez, S. J. Carbohydr. Chem.
2000, 19, 1319.
(13) Selected data of compound 4: pale yellow oil; 1H NMR (500
MHz, CDCl3): d (ppm) 8.02 (d, 1 H, J = 2.9 Hz, CH-
thiazole); 7.70 (d, 1 H, J = 2.9 Hz, CH-thiazole); 7.41 (d, 1
H, J = 15.7 Hz, H-1a); 7.25 (ddd, 1 H, J = 15.7 Hz, J = 7.1
Hz, J = 3.0 Hz, H-2a); 5.34 (dd, 1 H, J = 9.2 Hz, J = 8.9 Hz,
H-3); 5.13 (dd, 1 H, J = 8.9 Hz, J = 5.5 Hz, H-2); 4.96 (dd, 1
H, J = 8.87 Hz, J = 8.80 Hz, H-4); 4.42 (ddd, 1 H, J = 4.9 Hz,
J = 4.8 Hz, J = 5.5 Hz, H-1); 4.25 (dd, 1 H, J = 12.2 Hz, J =
6.0, H-6¢); 4.04 (dd, 1 H, J = 12.2 Hz, J = 2.1 Hz, H-6); 3.92
(m, H-5); 2.85 (m, 1 H, H-7), 2.63 (m, 1 H, H-7¢); 2.06, 2.05,
2.04, 2.00 (s, 4 × 3H, Ac). 13C NMR (125 MHz, CDCl3) d
(ppm) : 180.85 (CO-C=C); 170.55, 196.88, 169.5, 169.41,
169.37 (4 × O=C-CH3); 167.65 (thiazole C-2); 144.68 and
126.46 (2 × CH-thiazole); 144.62 and 126.46 (2 × -CH=);
71.16 (C-1); 69.87 (C-3); 69.73 (C-2); 69.17 (C-5); 68.40
(2) (a) Levy, D. E.; Tang, C. In The Chemistry of C-Glycosides,
Tetrahedron Organic Chemistry Series; Baldwin, J. E.;
Magnus, P. D., Eds.; Pergamon-Elsevier Science: Oxford,
1995. (b) Postema, M. H. D. In C-Glycoside Synthesis;
CRC: Boca Raton/ FL, 1995. (c) Vogel, P.; Ferrito, R.;
Kraehenbuehl, K.; Baudat, A. In Carbohydrate Mimics,
Concept and Methods; Chapleur, Y., Ed.; Wiley-VCH:
Weinheim, 1998, 19–48. (d) Du, Y.; Linhardt, R. J.; Vlahov,
I. R. Tetrahedron 1998, 54, 9913. (e) Vogel, P. Chimia
2001, 55, 359.
(3) (a) Wei, A.; Haudrechy, A.; Audin, C.; Jun, H.-S.;
Haudrechy-Bretel, N.; Kishi, Y. J. Org. Chem. 1995, 60,
2160. (b) Kobertz, W. R.; Bertozzi, C. R.; Bednarski, M. D.
J. Org. Chem. 1996, 61, 1894. (c) Streicher, H.; Geyer, A.;
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P. Štěpánek et al.
LETTER
(C-4); 61.90 (C-6); 29.74(C-7); 20.49, 20.47, 20.44, 20.38 (4
× O=C-CH3). ESI MS: 676.4 (M + H).
(16) Dondoni, A.; Marra, A.; Scherrmann, M.-C.; Bertolasi, V.
Chem.–Eur. J. 2001, 7, 1371.
(14) The NOE experiments with the obtained mixture of
cycloadducts proved the cis relative configurations on
dihydropyran ring in both componds 6 and 7. The NMR
spectra did not reveal any endo-cycloadducts in the reaction
mixture.
(15) Ethyl vinyl ether (1.5mL, 15 mmol) and Eu(fod)3 (460 mg,
0.4 mmol) were added to a solution of 5 (4 g, 6.2 mmol) in
dichloromethane (10.7 mL) and the reaction mixture was
sonicated for 6 h at room temperature. The solvent and the
excess ethyl vinyl ether were evaporated. Chromatography
of the residue (light petroleum–EtOAc, 8:1) afforded 2.05 g
(48%) of compound 8 (Rf = 0.29) and 1.94 g (46%) of
compound 9 (Rf = 0.42).
(17) A solution of aldehyde 10 (230 mg, 0.33 mmol) in
tetrahydrofuran (3.4 mL) was cooled to 0 °C and then treated
with 1 M solution of (CH3)2S·BH3 in tetrahydrofuran (0.69
mL, 0.69 mmol). The reaction mixture was stirred for 20 min
at 0 °C and for 18 h at room temperature. Then, 0.37 mL of
30% NaOH and 0.37 mL of 30% H2O2 were added at 0 °C,
and the solution was stirred at room temperature for 40 min.
After dilution with brine (10 mL), the solution was extracted
with ethyl acetate (3 × 10 mL), and the combined organic
layers were dried (Mg2SO4). Evaporation of the solvent
under reduced pressure and chromatography of the residue
(light petroleum–ethyl acetate 1:1) afforded 143 mg (60%)
of 12 (Rf = 0.5) as a colorless oil.
Selected data of compound 8: 1H NMR (500 MHz, CDCl3):
d (ppm) 7.83 (d, 1 H, J = 3.3 Hz, CH-thiazole); 7.17–7.32
(m, 21 H, 4 × C6H5, CH-thiazole); 6.08 (d, 1 H, J = 3.4 Hz,
H-4a); 5.20 (dd, 1 H, J = 2.1 Hz, J = 6.8 Hz, H-1a); 4.96–
4.48 (m, 8 H, 4 × C6H5-CH2); 4.30 (m, 1 H, H-1); 4.02 (dq,
1 H, J = 9.6 Hz, J = 7.0, -O-CH2-CH3); 3.82–3.62 (m, 8 H,
H-2, H-3, H-4, H-5, H-6, H-6¢, -O-CH2-CH3); 2.62 (m, 1 H,
H-3a); 2.17 (ddd, 1 H,, J = 2.1 Hz, J = 4.6 Hz, J = 11.5, H-
2aeq); 1.98 (m, 2 H, H-7, H-7¢); 1.88 (ddd, 1 H, J = 6.8 Hz, J
= 11.5 Hz, J = 11.5, H-2aax); 1.30 (t, 3 H, J = 7.0, -O-CH2-
CH3). 13C NMR (125 MHz, CDCl3) d (ppm): 164.62
(thiazole C-2); 143.73 (C-5a); 143.28 (CH-thiazole); 138.36,
138.27, 138.22, 138.12 (4 × ipso C6H5-CH2), 128.36-127.57
(20 × C6H5-CH2); 118.48 (CH-thiazole); 104.24 (C-4a);
99.61 (C-1a); 82.36, 80.13, 78.07, 72.31, 71.48 (C-1, C-2, C-
3, C-4, C-5); 75.42, 74.96, 73.53, 73.14 (4 × C6H5-CH2);
69.1 (C-6); 64.65 (O-CH2-CH3); 33.76 (C-2a); 30.22 (C-7);
27.67 (C-3a); 15.27 (O-CH2-CH3). ESI MS: 748.2 (M + H).
Selected data of compound 9: 1H NMR (500 MHz, CDCl3):
d (ppm) 7.82 (d, 1 H, J = 3.3 Hz, CH-thiazole); 7.15–7.38
(m, 21 H, 4 × C6H5, CH-thiazole); 5.97 (d, 1 H, J = 3.2 Hz,
H-4a); 5.20 (dd, 1 H, J = 1.7 Hz, J = 6.7 Hz, H-1a); 4.97–
4.50 (m, 8 H, 4 × C6H5-CH2); 4.25 (m, 1 H, H-1); 4.05 (dq,
1 H, J = 9.6 Hz, J = 7.0 Hz, O-CH2-CH3); 4.08–3.59 (m, 8 H,
H-2, H-3, H-4, H-5, H-6, H-6¢, O-CH2-CH3); 2.67 (m, 1 H,
H-3a), 2.22 (ddd, 1 H, J = 1.7 Hz, J = 2.6 Hz, J = 13.3 Hz,
H-2aeq); 2.09 (m, 1 H, H-7); 1.87 (m, 1 H, H-7¢); 1.75 (ddd,
1 H, J = 6.7 Hz, J = 13.3 Hz, J = 13.3 Hz, H-2aax); 1.30 (t, 3
H, J = 7.0 Hz, O-CH2-CH3). 13C NMR (125 MHz, CDCl3) d
(ppm): 164.40 (thiazole C-2); 143.86 (C-5a); 143.29 (CH-
thiazole); 138.68, 138.22, 138.04 (4 × ipso C6H5-CH2);
128.49-127.57 (20 × C6H5-CH2); 118.40 (CH-thiazole);
105.65 (C-4a); 99.85 (C-1a); 82.53, 79.95, 77.99, 71.45,
71.32 (C-1, C-2, C-3, C-4, C-5); 77.56, 76.36, 73.47, 72.83
(4 × C6H5-CH2); 68.89 (C-6); 64.74 (O-CH2-CH3); 32.36 (C-
2a); 30.16 (C-7); 27.15 (C-3a); 15.28 (O-CH2-CH3). ESI
MS: 748.2 (M + H).
(18) Selected data of compound 14: 1H NMR (CDCl3) : d (ppm)
5.25 (dd, 1 H, J = 9.4 Hz, J = 9.4 Hz, H-3); 4.98 (dd, 1 H,
J = 9.4 Hz, J = 5.7 Hz, H-2); 4.93 (dd, 1 H, J = 9.4 Hz, J =
9.2 Hz, H-4); 4.75 (dd, 1 H, J = 9.0 Hz, J = 10.0 Hz, H-4a);
4.52 (dd, 1 H, J = 1.0 Hz, J = 9.4 Hz, H-1a); 4.31–4.20 (m,
4 H, H-1, H-6a, H-6, H-6¢); 4.12 (dd, 1 H J = 2.2 Hz, J = 12.1
Hz, H-6a¢); 3.95 (m, 1 H, O-CH2-CH3); 3.85 (m, 1 H, H-5);
3.59–3.51 (m, 2 H, H-5a, -O-CH2-CH3); 2.20 (m, 1 H, H-
2aeq.); 2.14–2.04 (m, 19 H, 6 × Ac, H-7); 1.65 (m, 2 H, H-3a,
H-7¢); 1.54 (m, 1 H, H-2aax.); 1.23 (t, 1 H, J = 7.0 Hz, O-CH2-
CH3). 13C NMR (125 MHz CDCl3) d (ppm): 100.74 (C-1a);
74.50 (C-5a); 72.58 (C-1); 71.70 (C-4a); 70.05 (C-2); 69.56
(C-3); 68.77 (C-5); 68.66 (C-4); 64.67 (O-CH2-CH3); 62.63
(C-6); 62.38 (C-6a); 37.16 (C-2a); 36.00 (C-7); 27.50 (C-
3a); 20.50 (Ac); 15.00 (O-CH2-CH3). ESI MS: 627.3 (M +
Na).
Selected data of compound 17: 1H NMR (CDCl3) : d (ppm)
5.25 (dd, 1 H, J = 8.9 Hz, J = 8.9 Hz, H-3); 5.09 (dd, 1 H,
J = 9.2 Hz, J = 5.7 Hz, H-2); 4.94 (dd, 1 H, J = 8.9 Hz,
J = 8.9 Hz, H-4); 4.74 (dd, 1 H, J = 9.9 Hz, J = 9.9 Hz H-4a);
4.53 (d, 1 H, J = 8.1 Hz, H-1a); 4.33–4.18 (m, 4 H, H-1, H-
6a, H-6, H-6¢); 4.08 (dd, 1 H, J = 2.3 Hz, J = 12.1 Hz, H-6a¢);
3.96 (dq, 1 H, J = 9.2 Hz, J = 7.1 Hz, O-CH2-CH3); 3.82 (m,
1 H, H-5); 3.59–3.51 (m, 2 H, H-5a, O-CH2-CH3); 2.17–2.02
(m, 19 H, 6 × Ac, H-2aeq.); 1.99–1.87 (m, 2 H, H-7, H-3a);
1.41 (ddd, 1 H,, J = 8.1 Hz, J = 9.7 Hz, J = 12.7 Hz, H-2aax.);
1.3–1.18 (m, 1 H, H-7¢); 1.24 (t, 3 H, J = 7.1 Hz, -O-CH2-
CH3). 13C NMR (125 MHz CDCl3) d (ppm) : 101.22 (C-1a);
74.51 (C-5a); 70.44 (C-4a); 69.99 (C-3); 69.90 (C-2); 69.11
(C-4); 68.60 (C-5); 68.45 (C-1); 64.66 (O-CH2-CH3); 62.80
(C-6a); 62.1(C-6); 35.04 (C-2a); 34.41 (C-3a); 26.57 (C-7);
20.62 (Ac), 14.94 (O-CH2-CH3). ESI MS: 627.3 (M + Na).
(19) Crystallographic data for the structure 17 have been
deposited with the Cambridge Crystallographic Data Centre;
reference number CCDC 203383. Copies of the data can be
obtained on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (E-mail:
deposit@ccdc.cam.ac.u).
Synlett 2003, No. 7, 963–966 ISSN 1234-567-89 © Thieme Stuttgart · New York