A convenient method for the synthesis of cyclic trithiocarbonates on carbohydrate scaffolds

Article abstract of DOI:10.1016/S0040-4039(02)02529-7

An efficient regio- and stereoselective method for the synthesis of cyclic trithiocarbonates on carbohydrate skeleton is described. A freshly prepared solution of sodium trithiocarbonate reacts with cis-oriented epoxytriflate pentoses 7-11 to yield the co

Full text of DOI:10.1016/S0040-4039(02)02529-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 315–317
A convenient method for the synthesis of cyclic trithiocarbonates
on carbohydrate scaffolds
Muhammad Saeed,a,† Muhammad Abbas,a Raid J. Abdel-Jalil,b Muhammad Zahidc and
Wolfgang Voeltera,*
aAbteilung fu¨r Physikalische Biochemie des Physiologisch-chemischen Institut der Universita¨t, Hoppe-Seyler Strasse-4,
D-72076 Tu¨bingen, Germany
bChemistry Department, Faculty of Sciences and Arts, Hashmite University, Zarka, Jordan
cHEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270,
Pakistan
Received 10 September 2002; revised 6 November 2002; accepted 8 November 2002
Abstract—An efficient regio- and stereoselective method for the synthesis of cyclic trithiocarbonates on carbohydrate skeleton is
described. A freshly prepared solution of sodium trithiocarbonate reacts with cis-oriented epoxytriflate pentoses 7–11 to yield the
1
corresponding cyclic trithiocarbonates 12–16. Structures of all new compounds are established through MS, H and 13C NMR
techniques. © 2002 Published by Elsevier Science Ltd.
The preparation of monosaccharides in which one or
more oxygen atoms are replaced by a sulfur atom have
received considerable attention, primarily because these
compounds provide a route to the synthesis of deoxy-
sugar.1 Trithiocarbonate derivatives of carbohydrates
are versatile intermediates for the synthesis of
dithiosugars2 and dideoxysugars.3 Only a few methods
are available for the synthesis of such carbohydrate
derivatives, including the reaction of potassium methyl
xanthate on epoxide4 and episulphides5 or, in some
cases, the use of highly toxic thiophosgene gas.6
In the past, we have used the triflates of 2,3-anhydro-
ribopyranoside 7 and 8 as starting materials toward the
synthesis of either new and useful chiral building
blocks10 or biologically active natural product.11 The
strategy banks on difference in the reactivity between
the cis-oriented triflate at C-4, which acts as a powerful
leaving group, and the epoxide. This strategy enabled
us to control the regioselective nucleophilic displace-
ment of the triflate group to form trans-oriented sys-
tems which can be modified by further chemical
transformations. In this communication, a simple and
efficient route for the synthesis of cyclic trithiocarbon-
ates 12–16 from the epoxytriflates 7–11 is described.
The cis-oriented epoxytriflates were synthesized from
the partially blocked sugars 2–6, respectively, by reac-
tion with triflic anhydride in the presence of pyridine at
0°C (Scheme 1).12 Formation of the cyclic trithiocar-
bonates involved the addition of a red colored aqueous
The reaction of organic halides with sodium trithiocar-
bonate (Na2CS3) has been widely used for the prepara-
tion of disubstituted trithiocarbonates.7 It has been
demonstrated that alkyl mono- and dihalides, upon
treatment with sodium trithiocarbonate, could easily be
converted into corresponding mono- or dimercaptans.8
Recent efforts toward the preparation of dialkyl
trithiocarbonates9 prompted us to investigate the
epoxytriflates 7–11 as possible candidate of sugar-based
trithiocarbonates.
13
solution of Na2CS3 to a stirred solution of epoxytrifl-
ate.14 The nucleophilic displacement of triflyl group at
C-4 by sulfur was followed by the simultaneous
intramolecular ring opening of the epoxide to afford
the required trithiocarbonates in the yields given in
Table 1.
Structures of all products were established through MS,
* Corresponding author. E-mail: wolfgang.voelter@uni-tuebingen.de
† Present address: Eppley Institute for Research in Cancer and Allied
Diseases, University of Nebraska Medical Center, Omaha, NE
68198-6805, USA. E-mail: msaeed@unmc.edu
1
elemental analysis, H and 13C NMR spectroscopy.15
Conformations adopted by pyranoside rings in the
product 12 and 13 were determined by vicinal coupling
0040-4039/03/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)02529-7

316
M. Saeed et al. / Tetrahedron Letters 44 (2003) 315–317
Scheme 1. Synthesis of sugar-based trithiocarbonates. Reagents and conditions: (a) Aliquat 336®, H2O, 40°C, 90 min; (b) pyridine,
Tf2O, CH2Cl2, 0°C; (c) 1, ethanol, H2O, rt, 0.5 h.
Epoxyfuranosides 5 and 616 were triflated by the stan-
1
constants and chemical shifts of their H NMR spectra
dard method12 and treated with Na2CS3. The yields of
(Fig. 1). 5-H and 5%-H were recognized easily from their
the trithiocarbonates 15 and 16 were, however, very low
due to the reasons unknown to us. The reaction was
sluggish and many unknown side products are also
formed. The reason for the low yield may be due to low
reactivity of furanoside epoxide or instability of the
six-membered trithiocarbonate unit. Further investiga-
tions in this context are under observations in our
laboratory.
large geminal coupling constant (ꢀ13 Hz) at l=4.30
and 3.87 ppm, respectively, in 12, and at l=4.15 and
3.88 ppm, respectively in 13. A symmetrical ddd pattern
appeared for 4-H of 12 with J4,5=3.05, J4,5%=3.05 and
J
3,4=4.27 Hz. This indicated a quasi equatorial–quasi
equatorial relationship between 4-H and 5%-H and quasi
equatorial–axial relationship between 4-H and 5-H; the
conformation of the pyranoside ring in 12 is, therefore,
1
predominately C4. This was further supported by the
large axial–axial coupling constant for 1-H and 2-H
(J1,2=6.41 Hz). On the other hand in 13, 4-H appeared
as a multiplet at l=4.81 ppm buried under the signal
of the benzylidene proton. Although, the direct calcula-
tion of the coupling constants was not possible in this
case, the coupling interaction of 4-H with 5-H and 5%-H
ware calculated from dd patterns observed for the latter
protons, revealing a 1.83 Hz value for J4,5 and a 3.06
Hz value for J4,5%. From these assignments, we assumed
Table 1. Synthesis of trithiocarbonates on sugar scaffold
Entry
Epoxy
triflate
Trithio-
carbonate
Time
(min)
Yield
(%)
1
2
3
4
5
7
8
9
10
11
12
13
14
14
15
10
10
25
60
65
95
90
75
30
25
a
quasi equatorial position for 4-H; hence, the
pyranoside ring in 13 occurs predominately in 4C1
conformation (Fig. 1).

M. Saeed et al. / Tetrahedron Letters 44 (2003) 315–317
317
9. (a) Tamami, B.; Kiasat, A. R. J. Chem. Res. (S) 1998,
454; (b) Fanghanel, B.; Ullrich, A.; Wagner, C. Eur. J.
Org. Chem. 1998, 1577.
10. (a) Saeed, M.; Abdel-Jalil, R. J.; Voelter, W.; El-Abade-
lah, M. M. Chem. Lett. 2001, 7, 660; (b) Abdel-Jalil, R.
J.; Saeed, M.; Voelter, W. Tetrahedron Lett. 2001, 42,
2435.
11. Al-Abed, Y.; Naz, N.; Mootoo, D.; Voeter, W. Tetra-
hedron Lett. 1996, 37, 8641.
12. Buchanan, D.; Clode, D. M.; Vethaviyasar, N. J. J.
Chem. Soc., Perkin Trans. 1 1976, 1449.
13. Sundin, A.; Frejd, T.; Magnusson, G. J. Org. Chem.
1986, 51, 3927.
14. General method for the preparation of trithiocarbonates:
To a stirred solution of freshly prepared Na2CS3 (ꢀ2
mmol) in water (5 ml) was added a solution of epoxytrifl-
ate (1 mmol) in ethanol (1 ml) at room temperature. The
red color of Na2CS3 disappeared with the formation of
yellow colored precipitate. After the time indicated in the
Table 1, the precipitate was washed with water and
recrystallized with ethylacetate.
Figure 1. Preferred conformations of the pyranoside rings in
12 and 13 as determined from coupling interactions in 1H
NMR spectroscopy.
In conclusion, an easy and efficient method for the
synthesis of cyclic trithiocarbonates on a carbohydrate
scaffold has been discovered, which may lead to further
chemical modifications to prepare dithio- and/or
dideoxysugars.
15. Data for 12: yellow crystals; mp 131–133°C; 1H NMR
(250 MHz, CDCl3): l 7.36–7.38 (m, 5H, Ph), 4.95 (d,
J=11.9 Hz, 1H, OCHHPh), 4.76 (ddd, J=4.27, 3.05 Hz,
1H, H-4), 4.62 (d, J=11.9 Hz, 1H, OCHHPh), 4.46 (d,
J=6.41 Hz, 1H, H-1), 4.30 (dd, J=3.05, 13.42 Hz, 1H,
H-5), 4.07 (m, 2H, H-3, H-2), 3.87 (dd, J=3.35, 13.42
Hz, 1H, H-5%); 13C NMR (63 MHz, CDCl3): l 58.7, 61.4
(C-3, C-4), 61.6 (C-5), 69.9 (C-2), 70.8 (CH2Ph), 102
(C-1), 128.1, 128.3, 128.7 (Ph), 162.1 (CꢀS); FAB-MS:
m/z=314.1 (M+).
References
1. (a) Raymond, A. L. Advances in Carbohydrate Chemistry;
Academic Press: New York, 1995; p. 129; (b) McCasland,
D. E.; Zanglungo, A. B.; Durham, L. J. J. Org. Chem.
1974, 39, 1462.
1
Data for 13: yellow crystals; mp 162.3°C; H NMR (250
MHz, CDCl3): l 7.34–7.42 (m, 5H, Ph), 5.07 (brs, 1H,
H-1), 4.81 (m, 2H, H-4, OCHHPh), 4.61 (d, J=11.6 Hz,
1H, OCHHPh), 4.17 (m, 3H, H-5, H-3, H-2), 3.88 (dd,
J=1.83, 13.42 Hz, 1H, H-5%); 13C NMR (63 MHz,
CDCl3): l 56.8 (C-5), 60.1, 60.4 (C-3, C-4), 68.3 (C-2),
70.4 (CH2Ph), 97.05 (C-1), 128.3, 128.5, 128.8 (Ph); FAB-
MS: m/z=314.1 (M+).
2. Iqbal, S. M.; Owen, L. N. J. Chem. Soc. 1960, 1030.
3. McSweeney, G. E.; Wiggins, L. F. Nature 1951, 168, 874.
4. McCasland, G. E.; Zanglungo, A. B.; Durham, L. J. J.
Org. Chem. 1976, 41, 1125.
5. Craighton, A. M.; Owen, L. N. J. Chem. Soc. 1960, 1024.
6. (a) Duus, F. In Comprehensive Organic Chemistry; Bar-
ton, D.; Ollis, W. D., Eds.; Pergamon: New York, 1979;
Vol. 3, p. 342; (b) Bogemann, M.; Peterson, S.; Schultz,
O. E.; Soll, H. In Methoden der organischen Chemie;
Muller, E., Ed.; Houben-Weyl: Berlin, 1995; Vol. 9, p.
804.
1
Data for 15: yellow oil; H NMR (250 MHz, CDCl3): l
5.23 (s, 1H, H-1), 4.29 (t, J=7.3 Hz, 1H, H-4), 3.66 (m,
2H), 3.52 (2H), 3.35 (s, 3H, OCH3); 13C NMR (63 MHz,
CDCl3): l 28.3 (C-6), 55.6 (OCH3), 56.8 (C-3), 74.1, 75.7
(C-2, C-4), 104.3 (C-1); FAB-MS: m/z=238.1 (M+)
16. Anderson, C. D.; Goodman, L.; Baker, B. R. J. Am.
Chem. Soc. 1958, 80, 5247.
7. Reid, E. E. Organic Chemistry of Bivalent Sulfur; Chemi-
cal Publishing Company: New York, 1958.
8. Martin, D. J.; Greco, C. C. J. Org. Chem. 1968, 33, 1577.