LETTER
Triazole-Linked 1,6-a-D-Oligomannosides
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Supporting Information for this article is available online at
N3
OBn
O
BnO
BnO
N
N
References and Notes
N
OBn
O
(1) (a) The Return of the White Plague: Global Poverty and the
New Tuberculosis; Gaudy, M.; Zumla, A., Eds.; Verso:
London, 2003. (b) Ryan, F. The Forgotten Plague; Little,
Brown & Co.: Canada, 1992, 415.
CuI, i-Pr2EtN, DMF
MW, 80 °C, 30 min
BnO
BnO
6d
+
3
N
N
(2) Brennan, P. J.; Nikaido, H. Annu. Rev. Biochem. 1995, 64,
N
OBn
O
29.
BnO
BnO
(3) Morita, Y. S.; Patterson, J. H.; Billman-Jacobe, H.;
McConville, M. J. Biochem. J. 2004, 378, 589.
(4) (a) Khoo, K. H.; Dell, A.; Morris, H. R.; Brennan, P. J.;
Chatterjee, D. Glycobiology 1995, 5, 117. (b) Chatterjee,
D.; Hunter, S. W.; McNeil, M.; Brennan, P. J. J. Biol. Chem.
1992, 267, 6228.
OR1
O
11
OMOM
Me
R1O
R1O
(5) For the chemical synthesis of oligomannan and
oligoarabinan fragments and their lipoconjugates, see:
(a) Jayaprakash, K. N.; Chaudhuri, S. R.; Murty, C. V. S. R.;
Fraser-Reid, B. J. Org. Chem. 2007, 72, 5534. (b) Joe, M.;
Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am. Chem. Soc.
2007, 129, 9885. (c) Fraser-Reid, B.; Chaudhuri, S. R.;
Jayaprakash, K. N.; Lu, J.; Ramamurty, C. V. S. J. Org.
Chem. 2008, 73, 9732.
N
N
N
OR1
O
R1O
R1O
8
N
N
N
OR1
O
R1O
R1O
(6) Watt, J. A.; Williams, S. J. Org. Biomol. Chem. 2005, 3,
1982.
(7) For an earlier synthesis of triazole-mannose oligomers, see:
Cheshev, P.; Marra, A.; Dondoni, A. Org. Biomol. Chem.
2006, 4, 3225.
(8) Dalvie, D. K.; Kalgutkar, A. S.; Khojasteh-Bakht, S. C.;
Obach, R. S.; O’Donnell, J. P. Chem. Res. Toxicol. 2002, 15,
269.
OR2
12 R1 = Bn, R2 = CH2OMe (93%)
1. CF3CO2H, CH2Cl2, r.t., 3 h
2. BCl3, CH2Cl2, –60 to 0 °C, 2 h
3. Ac2O, Py, r.t., 16 h
13 R1 = R2 = Ac (66%)
14 R1 = R2 = H (99%)
(9) Horne, W. S.; Yadav, M. K.; Stout, C. D.; Ghadiri, M. R.
J. Am. Chem. Soc. 2004, 126, 15366.
NH3, MeOH, r.t., 18 h
(10) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless,
K. B. Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornoe,
C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057.
(11) The building block employed in the earlier synthesis was an
ethynyl a-D-C-mannoside. Therefore, each cycle was
constituted of the click azide–alkyne reaction and then
transformation of the 6-hydroxy into azido group in the
resulting product.
(12) It has to be noted that attempts to synthesize compound 4 by
addition of acetone to ethynyl 6-azido-2,3,4-tri-O-benzyl-6-
deoxy-a-D-C-mannopyranoside failed in our hands. The
basic conditions required for this process induced the 1,2-
elimination of benzyl alcohol leading to the undesired
glycal.
Scheme 3
by 1 M NH3 in methanol afforded the free hydroxy prod-
uct 14.
We believe we have paved the way to a new family of oli-
gomannose mimics that display two main features. One is
the interglycosidic triazole ring linked by a carbon–car-
bon bond to each mannose residue. The second is the pres-
ence of a capping 6-deoxymannose fragment in one side
of the chain. These features have been designed to make
the oligomers stable to enzymatic degradation and unable
to undergo mannosyltransferase-promoted glycosylation,
the key process for the Mycobacterium tuberculosis cell-
wall biosynthesis. Consequently, the free hydroxy hexam-
annoside 10 and decamannoside 14 appear to be interest-
ing substrates worth testing against that bacterium, the
etiological agent of tuberculosis. The synthesis of higher
homologues is under way, and the biological assays of all
the triazole-linked C-oligomannosides that have been pre-
pared will be carried out and reported in due course.
(13) Boyall, D.; López, F.; Sasaki, H.; Frantz, D.; Carreira, E. M.
Org. Lett. 2000, 2, 4233.
(14) Compound 9 in ref. 7 was treated with diphenylphosphoryl
azide (DPPA) and DBU under microwave irradiation
(120 °C, 2 h) to give 11 in 78% isolated yield (see
Supporting Information).
Synlett 2009, No. 16, 2679–2681 © Thieme Stuttgart · New York