Rhamnosylation reaction with a phenyl 1-thiorhamnoside and a rhamnosyl fluoride which have 4C1 conformation

Article abstract of DOI:10.1246/cl.2000.432

Rhamnosylation reaction with a phenyl 1-thiorhamnoside and a rhamnosyl fluoride that has chair conformation with more axial substituents (⁴C₁) is described. Flipping of the ring conformation changed the high α-selectivity of the gene

Full text of DOI:10.1246/cl.2000.432

432
Chemistry Letters 2000
Rhamnosylation Reaction with a Phenyl 1-Thiorhamnoside and a Rhamnosyl Fluoride Which
Have 4C1 Conformation
Hidetoshi Yamada* and Tomonari Ikeda
School of Science, Kwansei Gakuin University, Uegahara, Nishinomiya 662-8501
(Received January 20, 2000; CL-000056)
Rhamnosylation reaction with a phenyl 1-thiorhamnoside
and a rhamnosyl fluoride that has chair conformation with more
axial substituents (4C1) is described. Flipping of the ring con-
formation changed the high α-selectivity of the general rham-
nosylation reaction. More β-rhamnosides were afforded under
several conditions.
The O-rhamnosylation reactions generally show high α-
selectivity.1 Steric hindrance of the axial 2-O-substituent and
the stereoelectronic effect cause the selectivity. We recently
reported the chair conformation with more axial substituents of
L-rhamnopyranose.2 Flipping of the natural ring conformation
of L-rhamnose was occurred by introduction of TBS 3 for the 3-
OH group and TPS for the 4-OH group (1). Because both the
above-mentioned reasons of the α-selectivity deeply concerned
to its ring conformation, we were interested in the change of the
diastereoselectivity when the 'flipped' sugars were used as rham-
nosyl donors. We disclose here O-rhamnosylation reactions
with a phenyl 1-thiorhamnoside and a rhamnosyl fluoride that
has 4C1 conformation.4
Phenyl 1-thio-2-O-benzyl-3-O-TBS-4-O-TPS-α-L-rhamno-
pyranoside (2) was chosen as the glycosyl donor of our prelimi-
nary investigations. It was synthesized from an allyl rhamno-
2
side 3 in 99% yield by treatment with PhSTMS and ZnI2 in
1,2-dichloroethane at 50 °C for 2 h.5 Only the α-isomer was
thermodynamically obtained, and 2 kept the 4C1 conformation.12
The diastereoselectivity in the ethereal solvents and ace-
tonitrile can be understood considering the reverse anomeric
7
effect and nitrilium-nitrite conjugation (nitrile effect).8
Generally in O-glycosylation, the 1,2-cis- (α-) isomers are
selectively obtained in ethereal solvents by the reverse anomer-
ic effect.7,9 Although 2 is classified into D-gluco type around
the reaction center, the ratio of 1,2-trans- (α-) isomer is higher
than in the case of the corresponding glucosylation. The oxoni-
um cation 8 would be more stable than 9 by the reverse
anomeric effect. However, an approach of an alcohol from
lower face of 8, the reaction would be slower than the reaction
6
of 9 by a double 1,3-diaxial repulsion due to the oxygen sub-
stituent at C-3 and the methyl group of C-6. Therefore, the
reaction from the upper face of 9 became relatively increased to
give the 1,2-trans- (α-) isomer.
Generally in acetonitrile, conjugation from the axial site is
more stable when the glycosyl donor is D-gluco type to give
1,2-trans- (β-) glucosides.8,9 In the case with 2, the conjugation
from the axial site 9 would not be as stable as in the case with
D-glucose derivatives by the double 1,3-diaxial repulsion. The
ratio of the 1,2-cis- (β-) isomer, therefore, became relatively
higher through 8 when methanol was used as a rhamnosyl
acceptor (Table 1, entry 10). Bigger alcohol influenced the 1,3-
Reactions of 2 by NBS were achieved with methanol,
cyclohexylmethanol, and 2-propanol to give rhamnosides 4, 5,
and 6, respectively. Selection of solvents and size of the rham-
nosyl acceptors influenced the diastereoselectivity at the
anomeric position (Table 1). In dichloromethane, the α-isomer
was selectively obtained when the primary alcohols were used
as glycosyl donor (entries 1 and 2). In contrast, a reaction with
2-propanol showed β-selectivity (entry 3). In diethyl ether and
THF, the β-isomers were preferred (entries 4 - 9). In acetoni-
trile, none of the case showed the β-selectivity. Increasing size
of the alcohol resulted less β-isomer (entries 10 - 12). Derived
rhamnosides 4αβ, 5αβ, and 6αβ kept the 4C1 conformation.12
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
433
diaxial repulsion more than the solvent. Consequently, increas-
ing size of the glycosyl acceptors resulted in more 1,2-trans-
(α-) isomer through 9 (Table 1, entries 10-12).
exceeded the formation of the α-isomer.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports and
Culture, Japan (No. 10780359).
References and Notes
1
M. Nishizawa, H. Imagawa, E. Morikuni, S. Hatakeyama,
and H. Yamada, Chem. Pharm. Bull., 42, 1365 (1994); T.
Hosoya, E. Takashiro, T. Matsumoto, and K. Suzuki,
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García, and H. Yamada, Synlett, 1992, 797; G. H.
Veeneman, L. J. F. Gomes, and J. H. van Boom,
Tetrahedron, 45, 7433 (1989); P. Fügedi, A. Lipták, and
P. Nánási, Carbohydr. Res., 107, C5 (1982).
2
3
H. Yamada, M. Nakatani, T. Ikeda, and Y. Marumoto,
Tetrahedron Lett., 40, 5573 (1999).
Reactions of the corresponding rhamnosyl fluorides
showed a similar tendency. The fluoride 10 was prepared from
2 by treatment with DAST and NBS in dichloromethane at -40
°C.10 The derived 10 (77% yield) was a 69:31 mixture of α-
and β-isomers.12 Separated each isomer was independently
used for rhamnosylation reaction with cyclohexylmethanol
under Mukaiyama's conditions11 (AgClO4, SnCl2, 4A MS, -15
°C, 10 min) to give 5α and 5β (Table 2). Because both
diastereoisomers 10α and 10β showed similar diastereoselec-
tivity, the reaction passed through the same oxonium cation 7.
High α-selective reaction was observed in dichloromethane. In
contrast, unusual ratio of the β-isomer was obtained in diethyl
ether.
In this paper, the following abbreviations are used; DAST:
(diethylamino)sulfur trifluoride, TBS: tert-butyldimethyl-
silyl, TPS: tert-butyldiphenylsilyl. Others complied with a
standard list of abbreviations on J. Org. Chem., 64, 21A
(1999).
Equatorial selective C-glycosylation reactions have been
observed using 'flipped' sugars. T. Hosoya, Y. Ohashi, T.
Matsumoto, and K. Suzuki, Tetrahedron Lett., 37, 663
(1996); S. Manabe and Y. Ito, J. Am. Chem. Soc., 121,
9754 (1999).
S. Hanessian and Y. Guindon, Carbohydr. Res., 86, C3
(1980).
K. C. Nicolaou, S. P. Seitz, and D. P. Papahatjis, J. Am.
Chem. Soc., 105, 2430 (1983).
G. Wulff and G. Rohle, Angew. Chem., Int. Ed. Engl., 13,
157 (1974).
R. R. Schmidt, M. Behrendt, and A. Toepfer, Synlett, 1990,
694; Y. D. Vankar, P. S. Vankar, M. Behrendt, and R. R.
Schmidt, Tetrahedron, 47, 9985 (1991).
4
5
6
7
8
9
Because we could not find the exactly same reaction condi-
tions in the literature, reactions with phenyl 1-thio-2,3,4,6-
tetra-O-benzyl-α-D-glucoside (11) were also investigated.
When 11 was treated with cyclohexylmethanol under the
same conditions with the reactions of 2, the α/β ratios of
the resulting glucoside were 80:20 in CH2Cl2 (75% yield),
84:16 in Et2O (61% yield), and 15:85 in CH3CN (83%
yield).
10 K. C. Nicolaou, R. E. Dolle, D. P. Papahatjis, and J. L.
Randall, J. Am. Chem. Soc., 106, 4189 (1984); W.
Rosenbrook Jr, D. A. Riley, and P. A. Lartey, Tetrahedron
Lett., 26, 3 (1985).
11 T. Mukaiyama, Y. Murai, and S. Shoda, Chem. Lett., 1981,
431.
12 1H NMR coupling constants between neighboring protons
are following. The value (Hz) was shown in order of H1-
H2, H2-H3, H3-H4, and H4-H5 in parenthesis. 2: (9.2,
2.8, 2.8, and 2.8), 4α: (6.8, 2.4, 2.4, and 2.4), 4β: (3.7, 3.4,
4.4, and 2.2), 5α: (6.8, 2.4, 2.4, and 4.4), 5β: (3.4, 3.4, 4.4,
and 2.4), 6α: (6.9, 2.7, 2.4, and 3.3), 6β: (3.6, 3.0, 2.4, and
5.4), 10α: (6.0, 2.0, 2.0, and 5.6), 10β: (3.7, 3.2, 4.0, and
4.8).
In conclusion, during rhamnosylation reactions with rham-
nosyl donors that have 4C1 ring conformation, the conformation
was maintained. The diastereoselectivity at the anomeric center
was different from the case with rhamnosyl donors of normal
1C4 conformation. In some cases, the formation of the β-isomer