R. E. J. N. Litjens et al. / Tetrahedron Letters 42 (2001) 8693–8696
8695
Acknowledgements
revealed the presence of starting materials and no
trace of the expected coupling products. Moreover,
executing the activation step at higher temperatures
(−60−20°C) or prolonged reaction times was also not
successful. In addition, glycosidation at temperatures
above −20°C led to intractable mixtures of products.
Similar results were also obtained in subjecting the
ethylthio donor 5b to the same glycosidation
conditions.
The authors thank Fons Lefeber and Cees Erkelens for
recording the NMR spectra and Hans van den Elst for
performing the mass spectrometric analyses.
References
1. Kulaev, I. S.; Severin, A. I.; Stepnaya, O. A.; Kruglaya,
O. V. Biokhimiya 1989, 54, 201.
2. Likhosherstov, L. M.; Senchenkova, S. N.; Knirel, Y. A.;
Shashkov, A. S.; Shibaev, V. N.; Stepnaya, O. A.;
Kulaev, I. S. FEBS Lett. 1995, 368, 113.
The failure of activating donors 5a,b at low tempera-
ture can be explained16 by taking into consideration
that the nucleophilicity of the sulfur atom at the
anomeric center will be decreased due to the electron
withdrawing effect of the 2-azido group.17 It was there-
fore, envisaged that replacement of the anomeric func-
tions in 5a,b by the more electron donating
p-methoxyphenylthio group would have a beneficial
effect on the activation step. Indeed, it turned out that
activation of donor 5e,18 prepared in a similar fashion
as 5a,b (Scheme 1), for 15 min at −35°C followed by the
3. Stepnaya, O. A.; Severin, A. I.; Kulaev, I. S. Biokhimiya
1986, 51, 1117.
4. Stepnaya, O. A.; Ledova, L. A.; Kulaev, I. S. Bio-chem-
istry (Moscow) 1993, 58, 1523.
5. Kaji, E.; Lichtenthaler, F. W.; Nishino, T.; Yamane, A.;
Zen, S. Bull. Chem. Soc. Jpn. 1988, 61, 1291.
6. Kaji, E.; Lichtenthaler, F. W.; Osa, Y.; Takahashi, K.;
Zen, S. Bull. Chem. Soc. Jpn. 1995, 68, 2401.
7. Paulsen, H.; Lorentzen, J. P. Carbohydr. Res. 1984, 133,
C1.
8. Sato, K.-I.; Yoshimoto, A. Chem. Lett. 1995, 39.
9. Nilsson, M.; Norberg, T. J. Chem. Soc., Perkin Trans. 1
1998, 1699.
addition at −60°C of diacetone- -galactose 11, led to
D
the expected disaccharide 15 (entry 1 in Table 1)19 as a
mixture of anomers in good yield within 10 min. The
stereochemistry of the mannosidic bond in the resulting
individual anomers was firmly ascertained20 on the
basis of the C1ꢀH1 heteronuclear one-bond coupling
constants (1JC1,H1). An increase of b-selectivity was
observed (entry 2) in the glycosylation of methyl 2,3,4-
O-benzoyl-glucopyranoside 12 with 5e. On the other
hand, condensation of 5e (entry 3) with the relatively
more inert primary alcoholic function in the sphin-
gosine derivative 13 led to the exclusive formation,
although in moderate yield, of the 2-azido-2-deoxy-b-
mannoside 17. A similar result was observed (entry 4)
in the glycosidation of 5e with the secondary hydroxyl
group in acceptor 14. At this stage, it is also of interest
to note that the stereochemistry and yield of the man-
nosidations summarized in Table 1 do not deviate
substantially from those observed earlier by Crich and
10. Bousquet, E.; Khitri, M.; Lay, L.; Nicotra, F.; Panza, L.;
Russo, G. Carbohydr. Res. 1998, 311, 171.
11. Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321.
12. Crich, D.; Smith, M. Org. Lett. 2000, 25, 4067.
13. Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.
14. In a recent comparative study (see Ref. 21) towards the
b-selective low temperature glycosidation of 4,6-O-ben-
zylidene protected mannopyranosyl trichloroacet-imidate
4d and the similarly protected a-D-mannopyranosyl S-
ethyl sulfoxide, a twist-boat type intermediate was pro-
posed as the glycosylating species. This intermediate was
believed, for stereo-electronic and steric reasons, to favor
b-product formation.
15. Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett.
1996, 37, 6029.
Smith using the corresponding a- -thiomannoside 4b
D
as donor. However, the b-selectivity of the condensa-
tion of 5e with acceptor 12 (entry 2) is less pronounced
in comparison with the nearly exclusive formation of
the b-mannoside resulting from the coupling of the
corresponding partially acetylated glucose acceptor
16. Zuurmond, H. M.; Van der Laan, S. C.; Van der Marel,
G. A.; Van Boom, J. H. Carbohydr. Res. 1991, 215, C1.
17. Biffin, M. E. C.; Miller, J.; Paul, D. B. In The Chemistry
of the Azido Group; Patai, S., Ed.; John Wiley & Sons,
1971; p. 205.
with phenyl a- -thio-mannoside 4b.
D
1
18. All new compounds were fully characterized by H, 13C
1
NMR and MS. Relevant data of donor 5e: H NMR lH
In conclusion, the results thus far obtained indicate that
the readily accessible and orthogonally protected p-
(200 MHz, CDCl3): 7.58–7.30 (m, 12H), 6.86 (d, 2H, J
6.5 Hz), 5.63 (s, 1H), 5.26 (bs, 1H), 4.82 (AB, 2H), 4.35
(m, 1H), 4.20 (m, 4H), 3.82 (t, 1H, J 10.2 Hz), 3.77 (s,
3H). 13C NMR lC (50.1 MHz, CDCl3): 160.19, 137.93,
137.51, 135.14, 129.01, 128.53, 128.26, 127.89, 127.65,
126.19, 122.77, 114.94, 101.60, 87.89, 79.25, 75.88, 73.34,
68.30, 65.03, 63.88, 55.23. MS (ESI): m/z=528.4 (M+
Na)+.
methoxy-phenyl 2-azido-2-deoxy-a- -mannoside 5e
D
shows promise in the construction of the (13) cis-
linked ManpNAcA structural element of the target
molecule 1. Moreover, in analogy with the earlier
observed high b-mannoselectivity of the ethyl(phenyl)
sulfoxide11 4c and trichloroacetimidate21 4d donors, it
would also be of interest to examine the disarming
effect of the 2-azido group on the low temperature
activation of the corresponding 2-azido-2-deoxy donors
5c and 5d. Both aspects are currently under investiga-
tion and will be reported in due course.
19. General experimental procedure for the preparation of
2-azido-2-deoxy-D-mannosides 15–18: To a stirred solu-
tion of thiomannoside 5e (0.20 mmol), MPBT (66 mg,
0.25 mmol), DTBMP (102 mg, 0.5 mmol) and activated 3
,
A powdered molecular sieves in anhydrous dichloro-