Silver(I) oxide mediated selective monoprotection of diols in pyranosides

Article abstract of DOI:10.1021/jo0497252

The reaction of 4,6-O-benzylidene-D-pyranosides with a stoichiometric amount of TsCl, AcCl, and BzCl in the presence of silver(I) oxide and a catalytic amount of potassium iodide led to monosubstituted derivatives in high regioselectivity and in good yiel

Full text of DOI:10.1021/jo0497252

SCHEME 1. Regioselective P r otection of
Mu ltih yd r oxyl Gr ou p s
Silver (I) Oxid e Med ia ted Selective
Mon op r otection of Diols in P yr a n osid es
Haisheng Wang, J i She, Li-He Zhang, and Xin-Shan Ye*
The State Key Laboratory of Natural and Biomimetic
Drugs, School of Pharmaceutical Science, Peking University,
Xue Yuan Road #38, Beijing 100083, P. R. China
xinshan@bjmu.edu.cn
crowave irradiation technique,19-21 the dimethyltin dichlo-
ride procedure,22 and the Cu(II)-mediated acylation meth-
od23 are available, “genuine” synthetic solutions of these
compounds still await investigation. Recently, the silver(I)
oxide mediated monoprotection of symmetrical diols was
reported by Bouzide and Sauve´.24,25 Inspired by their re-
sults, we were interested in exploring the selective mono-
protection of 2,3-diols in 4,6-O-benzylidene galactopyra-
nosides or glucopyranosides by virtue of this approach.
First, a solution of p-methylphenyl 4,6-O-benzylidene-
1-thio-â-D-glucopyranoside (3)26 in dichloromethane was
treated with freshly prepared Ag2O and TsCl in the
presence of KI at room temperature yielding within 8 h
the 3-monosulfonate ester 10 in 97% isolated yield (Table
1, entry 3). No 2-substituted or 2,3-disubstituted product
was detected. After success of this example, we then tried
to use other carbohydrate substrates to test the selectiv-
ity of tosylation. As illustrated in Table 1, p-methylphe-
nyl-4,6-O-benzylidene-1-thio-â-D-galactopyranoside (2)26
and methyl 4,6-O-benzylidene-â-D-galactopyranoside (5)
also showed excellent selectivity and high yield for
monotosylation at 3-position (entry 2 and entry 5). When
methyl 4,6-O-benzylidene-R-D-galactopyranoside (6) was
treated using the same conditions as mentioned above,
a chromatographically inseparable mixture of the 3-to-
Received February 16, 2004
Abstr a ct: The reaction of 4, 6-O-benzylidene-D-pyranosides
with a stoichiometric amount of TsCl, AcCl, and BzCl in the
presence of silver(I) oxide and a catalytic amount of potas-
sium iodide led to monosubstituted derivatives in high
regioselectivity and in good yields.
Oligosaccharides and glycoconjugates play a crucial
role in a multitude of important biological processes.1 The
assembly of oligosaccharides and glycoconjugates is an
intensive field of research.2 Although enzymatic synthe-
sis3 of carbohydrates has shown advantages over chemi-
cal synthesis, its application is hampered by the fact
useful enzymes are not yet widely available. The chemical
synthesis of carbohydrates, which is traditionally a time-
consuming process mainly due to the extensive need for
protecting group manipulations, is still the method of
choice in most cases. Therefore, regioselective protection
of multihydroxyl groups in a monosaccharide building
block is in great demand for the construction of an
oligosaccharide. Herein, we wish to report a facile new
method for the regioselective monoprotection of 2,3-diols
in 4,6-O-benzylidene-protected pyranosides in the pres-
ence of silver(I) oxide (Ag2O) and a catalytic amount of
potassium iodide (KI) under neutral conditions using a
stoichiometric amount of protecting reagents (Scheme 1).
Oligosaccharides with 1f2 and/or 1f3 linkages are
abundant in nature.4 Suitable protected galactopyrano-
sides or glucopyranosides with one free hydroxyl group at
the 2- or 3-position are very useful building blocks widely
used in oligosaccharide synthesis. The regioselective pro-
tection of only one of the two similar secondary 2,3-dihy-
droxyl groups is frequently required. Usually, treatment
of these diols with a stoichiometric equivalent of protect-
ing reagents results in the formation of a mixture of the
2-protected, the 3-protected, and the 2,3-diprotected der-
ivative; thus, the selectivity is difficult to control. Al-
though some selective protection approaches such as the
phase-transfer method,5-7 the use of 1-(benzoyloxy)benzo-
triazole as the acylating reagent,8,9 the dibutyltin oxide
mediated selective monoprotection strategy,10-18 the mi-
(6) Szeja, W. Synthesis 1979, 821-822.
(7) Garegg, P. J .; Kvarnstro¨m, I.; Niklasson, A.; Niklasson, G.;
Svensson, S. C. T. J . Carbohydr. Chem. 1993, 12, 939-953.
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1991, 1015-1018.
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1568-1573.
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(12) Ricci, A.; Roelens, S.; Vannucchi, A. J . Chem. Soc., Chem.
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(19) Morcuende, A.; Valverde, S.; Herrado´n, B. Synlett 1994, 89-91.
(20) Herrado´n, B.; Morcuende, A.; Valverde, S. Synlett 1995,
455-458.
(1) Ernst, B., Hart, G. W., Sinay¨, P., Eds. Carbohydrates in
Chemistry and Biology; Wiley-VCH: Weinheim, 2000; Vols. 1-4.
(2) (a) J ung, K.-H.; Mu¨ller, M.; Schmidt, R. R. Chem. Rev. 2000,
100, 4423-4442. (b) Garegg, P. J . Adv. Carbohydr. Chem. Biochem.
1997, 52, 179-205. (c) Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1380-1419. (d) Toshima, K.; Tatsuta, K. Chem.
Rev. 1993, 93, 1503-1531. (e) Boons, G.-J . Tetrahedron 1996, 52,
1095-1121. (f) Seeberger, P. H.; Haase, W.-C. Chem. Rev. 2000, 100,
4349-4393. (g) Sears, P.; Wong, C.-H. Science 2001, 291, 2344-2350.
(3) Koeller, K. M.; Wong, C.-H. Nature 2001, 409, 232-240.
(4) Varki, A. Glycobiology 1993, 3, 97-130.
(21) Morcuende, A.; Ors, M.; Valverde, S.; Herrado´n, B. J . Org.
Chem. 1996, 61, 5264-5270.
(22) Maki, T.; Iwasaki, F.; Matsumura, Y. Tetrahedron Lett. 1998,
39, 5601-5604.
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Res. 2001, 332, 157-166.
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10.1021/jo0497252 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/16/2004
5774
J . Org. Chem. 2004, 69, 5774-5777

TABLE 1. Selective Mon op r otection of P yr a n osid es
sylated product 13 and the 2-tosylated product was
lation was carried out to further investigate the regiose-
lectivity. Treatment of glucoside 1 with benzoyl chloride,
silver oxide, and potassium iodide produced the 3-ben-
zoylated product 22 in 86% isolated yield and the
2-benzoylated product in 12% isolated yield (entry 15);
likewise, monosaccharides 4 and 5 also gave the 3-ben-
zoylated products 25 and 26 in good yields (entry 18 and
19). When the thiogalactoside 2, thioglucoside 3, and
O-galactoside 6 were reacted with benzoyl chloride under
the same conditions, the corresponding 2-substituted
products were isolated as the major products in 70%,
86%, and 87% yield, respectively (entries 16, 17, and
20).28 The reverse regioselectivity was once again de-
tected. It seems that tosylation and acylation are de-
pendent both on the reactivities among hydroxyl groups
and on the tosylating and acylating reagents. The reac-
obtained in a total yield of 98% with the ratio of 2.8:1
1
based on H and COSY NMR spectral analyses (entry 6).
When the mannose derivative 7 was used as the substrate,
the 3-tosylated product 14 was also gained in 75% isola-
ted yield (entry 7). On the other hand, methyl 4,6-O-ben-
zylidene-R-D-glucopyranoside (1)27 and methyl 4,6-O-ben-
zylidene-â-D-glucopyranoside (4) exhibited reverse regio-
selectivity to give the 2-tosylated product 8 in 83% and
11 in 88% isolated yield (entries 1 and 4). Acetylation
was also performed utilizing these carbohydrate deriva-
tives as reactants. They generally exhibited good selec-
tivity and good yields (entries 8-14), leading to either
3-substituted or 2-substituted products. For the acety-
lation of saccharides 1, 2, 4, and 5, the 3-acetylated
products were obtained (entries 8, 9, 11, and 12). On the
contrary, for the acetylation of saccharides 3, 6, and 7,
reverse regioselectivity (acetylation at 2-position) was
again observed (entries 10, 13, and 14). Finally, benzoy-
(28) The reaction of mannose derivative 7 with BzCl was also tried.
The desired monobenzoylated product was too unstable to purify by
column chromatography. The benzoyl group migrated from one hydroxyl
to another hydroxyl position during standing and separation process, and
we finally got the mixture of 2- and 3-benzoylated product in a ratio
of ∼1:1.
(27) Iacazio, G.; Rorberts, S. M. J . Chem. Soc., Perkin Trans. 1 1993,
1099-1101.
J . Org. Chem, Vol. 69, No. 17, 2004 5775

SCHEME 2. In ter n a l Hyd r ogen Bon d in g
ed rates for the protection and led to hydrolysis of the
protecting reagents. Tetrahydrofuran (THF) was also
avoided since ring opening of THF was catalyzed by
Ag2O.24,31
In conclusion, we report a new method for the highly
selective monoprotection of pyranosides. Due to its
simplicity and its mild conditions, the reaction may find
wide application in saccharide synthesis. And the mech-
anism of the regioselectivity will still await investigation.
tivities of different hydroxyl groups may be connected
with the different acidities between 2- and 3-hydroxyl
groups, which come from the mutual effects on the struc-
tural nature of saccharides and the substituents at 1-posi-
tion. Based on our experimental results (Table 1), it
appears that (1) acetylation and benzoylation almost dis-
play the same regioselectivity (compare entries 8 and 10-
13 with entries 15 and 17-20) with the exception of thio-
galactoside 2 (compare entry 9 with entry 16); (2) mono-
tosylation at the 2- or 3-position depends on the anomeric
substituents (compare entries 3 and 4) but not the
anomeric configurations; this can be seen by that the
anomers 1/4 and 5/6 over tosylation show the same
regioselectivity (compare entries 1 and 4, 5 and 6); (3)
for the glucose series, the regioselectivity does not depend
on the anomeric configurations of saccharides (compare
entries 1 and 4, 8 and 11, and 15 and 18); (4) for the
glucose series, the change from O- to S-glycoside always
modifies the regioselectivity (compare entries 1, 4 and
3, entries 8, 11 and 10, and entries 15, 18 and 17).
We may attribute this highly selective monoprotection
of the pyranosides to an internal hydrogen bonding (IHB)
interaction25 (Scheme 2). The hydrogen atom Ha involved
in the IHB becomes less acidic than Hb, so Hb will be
first deprotonated by Ag2O. When the hydroxyl group
(Hb) with a lower PKa is deprotonated by Ag2O, IHB will
further decrease the acidity of the other hydroxyl group
(Ha). It therefore amplifies the discrimination of the two
hydroxyl groups, leading to a high level of regioselectivity.
In some cases, the anomeric R-methoxyl group may
probably participate in the formation of an internal
hydrogen bonding with 2-hydroxyl group, resulting in
outcomes of the 2-substituted product (see Table 1,
entries 13 and 20). The steric factor may also influence
the regioselectivity besides the internal hydrogen bond-
ing; as observed, most galactose derivatives tend to
undergo the substitutions at the 3-position (see Table 1,
entries 2, 5, 6, 9, 12, and 19). Another issue that should
be noted is that at least in some cases our results appear
to show the reverse regioselectivity compared with the
established organotin-mediated selective manipulation
practice which usually produced 2-substituted products,
for example, the benzoate ester at 2-position10,22 for
benzoylation of methyl 4,6-O-benzylidene-R-D-glucopy-
ranoside (1). In our case, the 3-substituted benzoylated
product was obtained. Another example is the tosylation
of methyl 4,6-O-benzylidene-â-D-glucopyranoside (4), which
gave the 3-substituted product under the conditions of
TsCl-pyridine,29 but by our approach the 2-substituted
product was gained (Table 1, entry 4). The different
regioselectivity can meet the requirements for the syn-
thesis of different saccharide building blocks.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r e. To a stirred solution
of p-methylphenyl-4,6-O-benzylidene-1-thio-â-D-glucopyranoside
(3) (2.0 g, 5.35 mmol) in dichloromethane (50 mL) were added
fresh Ag2O32 (1.91 g, 8.23 mmol), TsCl (1.28 g, 6.71 mmol), and
KI (0.19 g, 1.14 mmol). The reaction mixture was stirred for 8 h
at room temperature, filtered through a small pad of silica gel,
and washed with dichloromethane. Evaporation of the solvent
followed by column chromatography (petroleum ether/ethyl
acetate 8:1) gave the monotosylated product 10 (2.74 g, 97%) as
white crystals. For compound 10: 1H NMR (CDCl3, 500 MHz) δ
7.69 (td, 2H, J ) 2.0, 8.5 Hz), 7.43 (td, 2H, J ) 1.5, 8.0 Hz),
7.32-7.38 (m, 4H), 7.27 (m, 1H), 7.15 (d, 2H, J ) 8.0 Hz), 6.98
(d, 2H, J ) 8.0 Hz), 5.33 (s, 1H), 4.73 (dd, 1H, J ) 9.5, 8.0 Hz),
4.59 (d, 1H, J ) 9.5 Hz), 4.35 (dd, 1H, J ) 4.5, 10.5 Hz), 3.70 (t,
1H, J ) 10.0 Hz), 3.58 (dt, 1H, J ) 2.0, 9.0 Hz), 3.53 (t, 1H, J )
9.5 Hz), 3.46 (dt, 1H, J ) 5.0, 10.0 Hz), 3.11 (d, 1H, J ) 2.0 Hz),
2.36 (s, 3H), 2.29 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 21.19,
21.64, 68.38, 70.49, 70.83, 77.71, 83.04, 88.58, 101.60, 126.23,
126.61, 128.09, 128.14, 129.12, 129.30, 129.91, 133.25, 134.18,
136.49, 139.12, 144.55; MS (FAB) m/z 528 [M+]. Anal. Calcd for
C27H28O7S2: C, 61.34; H, 5.34. Found: C, 61.70; H, 5.32.
Compound 8. This compound was prepared from 1, yielding
8 by column chromatography (petroleum ether/ethyl acetate 10:
1): 1H NMR (CDCl3, 300 MHz) δ 7.83 (d, 2H, J ) 8.4 Hz), 7.44-
7.31(m, 7H), 5.47 (s, 1H), 4.82 (d, 1H, J ) 3.6 Hz), 4.37 (dd, 1H,
J ) 9.0, 4.2 Hz), 4.25 (dd, 1H, J ) 9.9, 4.2 Hz), 4.12 (t, 1H, J )
9.6 Hz), 3.84-3.76 (m, 1H), 3.69 (t, 1H, J ) 10.0 Hz), 3.45 (t,
1H, J ) 10.0 Hz), 3.34 (s, 3H), 2.43 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 21.69, 55.68, 61.89, 68.36, 68.73, 79.41, 80.97, 98.15,
101.98, 126.21, 128.07, 128.31, 129.28, 129.79, 133.19, 136.76,
145.17; MS (FAB) m/z 436 [M+]. Anal. Calcd for C21H24O8S: C,
57.79; H, 5.54. Found: C, 57.30; H, 5.46.
Compound 9. This compound was prepared from 2, yielding
9 by column chromatography (petroleum ether/ethyl acetate
8:1): 1H NMR (CDCl3, 300 MHz) δ 7.71 (d, 2H, J ) 5.1 Hz),
6.95 (d, 2H, J ) 7.8 Hz), 7.44 (d, 2H, J ) 7.8 Hz), 7.27-7.29 (m,
7H), 5.26 (s, 1H), 4.50 (dd, 1H, J ) 3.5 , 10.0 Hz), 4.38 (d, 1H,
J ) 9.0 Hz), 4.30 (m, 2H), 4.26 (d, 1H, J ) 7.0, 13.0 Hz), 4.05 (d,
1H, J ) 12.6 Hz), 3.76 (t, 1H, J ) 9.6 Hz), 3.46 (s, 1H), 2.33 (s,
3H), 2.25 (s, 3H); MS (FAB) m/z 528 [M+]. Anal. Calcd for
C27H28O7S2: C, 61.34; H, 5.34. Found: C, 61.38; H, 5.69.
Compound 11. This compound was prepared from 4, yielding
11 by column chromatography (petroleum ether/ethyl acetate
8:1): 1H NMR (CDCl3, 500 MHz) δ 2.44 (s, 3H), 2.87 (d, 1H, J )
3.0 Hz), 3.30 (s, 3H), 3.40 (dt, 1H, J ) 5.0, 10.0 Hz), 3.56 (t, 1H,
J ) 9.5 Hz), 3.75 (t, 1H, J ) 10.0 Hz), 3.95 (td, 1H, J ) 3.0, 9.5
Hz), 4.40 (d, 1H, J ) 7.5 Hz), 4.37 (t, 1H, J ) 6.5 Hz), 4.34 (dd,
1H, J ) 5.0, 10.0 Hz), 5.53 (s, 1H), 7.32-7.37 (m, 5H), 7.46-
7.48 (m, 2H), 7.82-7.84 (m, 2H). 13C NMR (CDCl3, 125 MHz) δ
21.64, 57.30, 65.97, 68.42, 71.89, 80.24, 82.27, 101.75, 101.86,
126.22, 128.27, 128.32, 129.29, 129.43, 133.83, 136.70, 144.80;
(30) Using ethyl acetate, toluene, or 1,2-dichloroethane as solvent,
similar results (yields and product ratios) were also obtained. Because
1,2-dichloroethane is more toxic and the solubility of saccharides in
ethyl acetate or toluene is not good, we eventually chose dichlo-
romethane as the solvent to perform the reaction.
Other solvents such as ethyl acetate, toluene, and 1,2-
dichloroethane also gave satisfactory results.30 However,
acetonitrile was an unsuitable solvent that gave decreas-
(31) Marshall, J . A.; Seletsky, B. M.; Luke, G. P. J . Org. Chem. 1994,
59, 3413-3420.
(32) Tanabe, M.; Peters, R. H. Organic Syntheses; Wiley: New York,
1990; Collect. Vol. VII, pp 386-392.
(29) In contrast, we treated methyl 4,6-O-benzylidene-â-D-glucopy-
ranoside (4) with TsCl and pyridine, the 3-tosylated product was
isolated in 48% yield as the major product.
5776 J . Org. Chem., Vol. 69, No. 17, 2004

MS (ESI) m/z 454 [M + NH4+]. Anal. Calcd for C21H24O8S: C,
57.79; H, 5.54. Found: C, 57.77; H: 5.82.
Compound 18. This compound was prepared from 4, yielding
18 by column chromatography (petroleum ether/ethyl acetate
10:1): 1H NMR (CDCl3, 500 MHz) δ 2.13 (s, 3H), 2.62 (br, 1H),
3.51-3.58 (m, 2H), 3.59 (s, 3H), 3.64 (t, 1H, J ) 9.5 Hz), 3.79 (t,
1H, J ) 10.0 Hz), 4.37 (dd, 1H, J ) 5.0, 10.0 Hz), 4.38 (d, 1H, J
) 7.5 Hz), 5.22 (t, 1H, J ) 9.5 Hz), 5.50 (s, 1H), 7.35-7.38 (m,
3H), 7.44-7.46 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 20.97,
57.62, 66.46, 68.61, 73.44, 73.58, 78.46, 101.49, 104.52, 126.12,
128.23, 129.09, 136.88, 171.03; MS (ESI) m/z 342 [M + NH4+].
Anal. Calcd for C16H20O7: C, 59.25; H, 6.22. Found: C, 59.37;
H, 6.09.
Compound 12. This compound was prepared from 5, yielding
12 by column chromatography (petroleum ether/ethyl acetate
6:1): 1H NMR (CDCl3, 300 MHz) δ 7.75 (d, 2H, J ) 8.1 Hz),
7.71-7.36 (m, 7H), 5.27 (s, 1H), 4.50 (dd, 1H, J ) 3.6 Hz, J )
9.6 Hz), 4.20-4.25 (m, 2H), 4.14 (d, 1H, J ) 7.8 Hz), 3.84-3.96
(m, 2H), 3.46 (s, 3H), 3.37 (s, 1H), 2.34 (d, 1H, J ) 2.7 Hz), 2.31
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 21.63, 57.24, 66.06, 68.36,
68.76, 74.09, 80.35, 100.84, 103.60, 126.14, 127.84, 128.00,
128.93, 129.63, 133.80, 137.20, 144.90; MS (ESI) m/z 454 [M +
NH4+]. Anal. Calcd for C21H24O8S: C, 57.79; H, 5.54. Found: C,
57.68; H, 5.68.
Compound 13. This compound was prepared from 6, yielding
13 by column chromatography (petroleum ether/ethyl acetate
5:1): 1H NMR (CDCl3, 500 MHz) δ 2.41 (s, 3H), 3.44 (s, 3H),
3.67 (br s, 1H), 4.04 (d, 1H, J ) 1.5 Hz), 4.15 (dd, 1H, J ) 3.5,
9.5 Hz), 4.25-4.27 (m, 1H), 4.36 (d, 1H, J ) 3.5 Hz), 4.82 (dd,
1H, J ) 3.5, 9.5 Hz), 4.90 (d, 1H, J ) 3.5 Hz), 5.39 (s, 1H), 7.28-
7.46 (m, 7H), 7.84 (d, 2H J ) 8.5 Hz); 13C NMR (CDCl3, 75 MHz)
δ 21.65, 55.73, 62.44, 66.32, 68.92, 74.76, 78.65, 100.17, 100.65,
126.05, 127.80, 128.07, 128.96, 129.67, 133.97, 137.23, 144.84;
MS (ESI) m/z 454 [M + NH4+].
Compound 19. This compound was prepared from 5, yielding
19 by column chromatography (petroleum ether/ethyl acetate
8:1): 1H NMR (CDCl3, 300 MHz) δ 2.14 (s, 3H), 2.43 (br., 1H),
3.51 (d, 1H, J ) 1.5 Hz), 3.59 (s, 3H), 4.01 (dd, 1H, J ) 7.5, 10.0
Hz), 4.07 (dd, 1H, J ) 1.5, 7.5 Hz), 4.29 (d, 1H, J ) 7.5 Hz),
4.34 (dd, 1H, J ) 1.5, 12.5 Hz), 4.40 (dd, 1H, J ) 1.0, 3.5 Hz),
4.86 (dd, 1H, J ) 3.5, 10.0 Hz), 5.50 (s, 1H), 7.33-7.38 (m, 3H),
7.48-7.51 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 57.24, 66.44,
68.50, 68.99, 73.28, 73.79, 100.89, 103.99, 126.24, 128.10, 128.97,
137.54, 171.04; MS (ESI) m/z 342 [M + NH4+]. Anal. Calcd for
C
16H20O7: C, 59.25; H, 6.22. Found: C, 59.03; H, 6.42.
Compound 20. This compound was prepared from 6, yielding
Compound 14. This compound was prepared from 7, yielding
14 by column chromatography (petroleum ether/ethyl acetate
8:1 containing 2% of Et3N): 1H NMR (CDCl3, 500 MHz) δ 2.36
(s, 3H), 2.37 (s, 3H), 2.78 (br s, 1H), 3.82 (t, 1H, J ) 10.5 Hz),
4.16 (t, 1H, J ) 9.5 Hz), 4.18 (dd, 1H, J ) 5.0, 10.5 Hz), 4.32
(td, 1H, J ) 5.0, 10.5 Hz), 4.59 (br s, 1H), 4.84 (dd, 1H, J ) 3.5,
10.0 Hz), 5.44 (s, 1H), 5.52 (s, 1H), 7.11 (d, 2H, J ) 8.0 Hz),
7.16 (d, 2H, J ) 8.0 Hz), 7.27 (d, 2H, J ) 8.0 Hz), 7.34-7.40 (m,
5H), 7.78 (d, 2H, J ) 8.0 Hz); MS (ESI) m/z 546 [M + NH4+].
Compound 15. This compound was prepared from 1, yielding
15 by column chromatography (petroleum ether/ethyl acetate
8:1): 1H NMR (CDCl3, 300 MHz) δ 7.47∼7.29 (m, 5H), 5.50 (s,
1H), 5.33 (t, 1H, J ) 9.6 Hz), 4.81 (d, 1H, J ) 4.2 Hz), 4.30 (dd,
1H, J ) 4.5, 9.3 Hz), 3.63-3.91 (m, 3H), 3.59 (t, 1H, J ) 9.6
Hz), 3.43 (s, 3H), 2.25 (s, 3H); MS (FAB) m/z 325 [M + H+]. Anal.
Calcd for C16H20O7: C, 59.25; H, 6.22. Found: C, 59.09; H, 6.20.
Compound 16. This compound was prepared from 2, yielding
16 by column chromatography (petroleum ether/ethyl acetate
10:1): 1H NMR (CDCl3, 300 MHz) δ 7.57 (d, 2H, J ) 7.8 Hz),
7.29-7.40 (m, 5H), 7.07 (d, 2H, J ) 7.8 Hz), 5.46 (s, 1H), 4.90
(dd, 1H, J ) 3.3, 12.0 Hz), 4.55 (d, 1H, J ) 9.3 Hz), 4.37 (m,
2H), 4.02 (dd, 1H, J ) 1.5, 12.0 Hz), 3.90 (t, 1H, J ) 9.6 Hz),
3.60 (s, 1H), 2.60 (br, 1H), 2.34 (s, 3H), 2.13 (s, 3H); MS (FAB)
m/z 455 [M + K+]. Anal. Calcd for C22H24O6S: C, 63.44; H, 5.81.
Found: C, 63.69; H, 5.82.
20 by column chromatography (petroleum ether/ethyl acetate
6:1): 1H NMR (CDCl3, 300 MHz) δ 2.15 (s, 3H), 2.40 (d, 1H, J )
10.5 Hz), 3.40 (s, 3H), 3.74 (br s, 1H), 4.07-4.12 (m, 2H), 4.28-
4.32 (m, 2H), 4.98 (d, 1H, J ) 3.6 Hz), 5.16 (dd, 1H, J ) 3.6 Hz,
J ) 10.2 Hz), 5.57 (s, 1H), 7.37-7.40 (m, 3H), 7.50-7.52 (m,
2H); 13C NMR (CDCl3, 75 MHz) δ 21.05, 45.72, 55.53, 62.32,
67.15, 69.13, 71.19, 98.11, 101.35, 126.28, 128.26, 129.26, 137.30,
171.04; MS (ESI) m/z 342 [M + NH4+].
Compound 21. This compound was prepared from 7, yielding
21 by column chromatography (petroleum ether/ethyl acetate
6:1): 1H NMR (CDCl3, 500 MHz) δ 2.16 (s, 3H), 2.33 (s, 3H),
2.42 (br s, 1H), 3.84 (t, 1H, J ) 10.0 Hz), 3.98 (t, 1H, J ) 10.0
Hz), 4.24 (d, 1H, J ) 5.0 Hz), 4.25 (d, 1H, J ) 5.0 Hz), 4.38 (dt,
1H, J ) 5.0, 10.0 Hz), 5.40 (br s, 1H), 5.48 (dd, 1H, J ) 1.0, 3.0
Hz), 5.62 (s, 1H), 7.13 (d, 2H, J ) 8.0 Hz), 7.36 (d, 2H, J ) 8.0
Hz), 7.38-7.39 (m, 3H), 7.51-7.53 (m, 2H); 13C NMR (CDCl3,
125 MHz) δ 20.97, 21.12, 64.5, 67.74, 68.40, 73.54, 79.14, 87.25,
102.24, 126.25, 128.37, 129.21, 129.32, 129.98, 132.71, 137.01,
138.38, 170.35; MS (ESI) m/z 434 [M + NH4+].
Ack n ow led gm en t. This work was financially sup-
ported by the National Natural Science Foundation of
China. J .S. is on study leave from Guangdong Medical
College, Zhanjiang, China.
Compound 17. This compound was prepared from 3, yielding
17 by column chromatography (petroleum ether/ethyl acetate
8:1): 1H NMR (CDCl3, 500 MHz) δ 7.43-7.48 (m, 2H), 7.34-7.39
(m, 5H), 7.13 (d, 2H, J ) 7.5 Hz), 5.53 (s, 1H), 4.91 (dd, 1H, J )
9.0, 10.0 Hz), 4.67 (d, 1H, J ) 10.0 Hz), 4.38 (dd, 1H, J ) 5.0,
10.5 Hz), 3.91 (dt, 1H, J ) 3.5, 9.0 Hz), 3.78 (t, 1H, J ) 10.0 Hz),
3.54 (t, 1H, J ) 9.0 Hz), 3.46∼3.51 (m, 1H), 2.49 (d, 1H, J ) 3.0
Hz), 2.35 (s, 3H), 2.19 (s, 3H); MS (FAB) m/z 416 [M+]. Anal.
Calcd for C22H24O6S: C, 63.44; H, 5.81. Found: C, 63.07; H, 5.74.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for compounds 22-27.
Selected 1H NMR, 13C NMR, and 2D NMR spectra for
compounds 8-27. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O0497252
J . Org. Chem, Vol. 69, No. 17, 2004 5777