S.-C. Hung et al.
COMMUNICATION
Scheme 3. Reagents and conditions: a) cat. ScACHTUNTGRNEUNG(OTf)3, Ac2O, 0 8C, 5 h,
then H2C=CHCH2OH, BF3·OEt2, 3 ꢂ M.S., ꢀ168C, 18 h, 18: 37%, 19:
41%; b) DDQ, CH2Cl2/H2O=18:1, RT, 2 h, 78%; c) TFA, Ac2O, 0 8C!
RT, 24 h, 97 %; d) 1. NH3(g)
, MeOH/THF=1:5, 08C, 18 h, 91%;
2. CCl3CN, K2CO3, CH2Cl2, RT, 14 h, 89%; e) AgOTf, 5, CH2Cl2, ꢀ788C,
1 h, 14%. M.S.=molecular sieves, TFA=trifluoroacetic acid.
that the H1 and H2 protons of compound 18 possess a trans-
diaxial relationship. The NOESY spectrum of 18 exhibited a
through-space cross-interaction of the H1 proton with the
H5 proton, but not with the H2 proton, confirming that the
glycosidic bond of 18 is b-linked. The opposite phenomenon,
observed in the NOESY spectrum of 19, showed the stereo-
chemistry to be the a form. These spectral techniques were
used to characterize the a or b configuration of the newly
formed glycosidic bonds throughout the study. Treatment of
compound 19 with DDQ yielded the desired 4-alcohol 5
(78%), which could be applied as a glycosyl acceptor. For
the preparation of the glycosyl donor 4, three steps were
needed for the conversion from the ether 17. Treatment of
17 under acetolysis conditions afforded the 1,6-diacetate 20
in excellent yield (97%). Regioselective O1-deacetylation of
20 with ammonia led to the lactol (91%), which was treated
with trichloroacetonitrile and potassium carbonate to fur-
nish the expected product 4 in 89% yield. To our dismay,
TMSOTf-activated coupling of compound 4 with the 4-alco-
hol 5 failed to give the desired disaccharide 21, whereas
AgOTf as a promoter provided 21 in low yield (14%), pre-
sumably owing to the steric barrier imposed by the axial 4-
hydroxy group of 5.
Scheme 4. Reagents and conditions: a) NaH, BnBr, DMF, 08C!RT,
15 h, 96%; b) 1. ScACTHNUTRGNE(UNG OTf)3, Ac2O, RT, 2.5 h, 97%; 2. NH3(g), MeOH/
THF=1:4, 08C, 18 h, 96%; c) CCl3CN, K2CO3, CH2Cl2, RT, 5 h, 6: 91%,
26, 89%; d) cat. TMSOTf, 7, 4 ꢂ M.S., CH2Cl2, ꢀ868C, 1 h, 24: 70%,
24b: 17%; e) 1. TFA, Ac2O, 0 8C, 16 h; 2. H2NNH2·AcOH, DMF, 08C!
RT, 6 h, 79% in two steps; f) tBuOK, H2C=CHCH2Br, tBuOH, 08C, 2 h,
27: 79%. TMSOTf=trimethylsilyl trifluoromethanesulfonate.
(J1’,2’ =3.4 Hz) and its b isomer (J1’,2’ =8.0 Hz) in 70% and
17% yields, respectively. Cleavage of the 1,6-anhydro ring
in 24 with TFA and Ac2O followed by removal of the O1-
acetyl group with H2NNH2·HOAc gave the corresponding
lactol 25 (79%, a/b=1:1) in two steps. Initial attempts for
allylation of the imidate 26, prepared from 25 in 89% yield,
with allyl alcohol employing TMSOTf as the catalyst un-
fortunately provided the desired a form compound 27 (8%,
J
1,2 =3.8 Hz) in a low yield along with the major b isomer 28
(68%). In sharp contrast, coupling of the 1-alcohol 25 with
allyl bromide via Williamson etherification using potassium
tert-butoxide as a base furnished the a-linked molecule 27
(79%) as a single product. It should be noted that the acetyl
groups remained unaffected under these basic conditions.
The high stereoselectivity is perhaps induced by the chela-
tion effect of potassium cation with C1-alkoxide and the
lone-pair electrons of O2, preferring the 1,2-cis configura-
tion.[21]
Scheme 5 delineates the chain elongation of the GG di-
saccharide and deprotection sequences to obtain alginate
oligosaccharides. TMSOTf-catalyzed coupling of the imidate
donor 26 with the 4-alcohol 7 afforded the a-linked trisac-
charide 29 (78%, J1’,2’ =3.3 Hz) exclusively. Acetolysis of 29
followed by anomeric deacetylation led to the trisaccharide
hemiacetal 30 (72% overall yield in two steps), which was
Alternatively, the other strategy, “from the nonreducing
end to the reducing end” using the 1,6-anhydro-b-l-gulopyr-
anose 7 as a repeating glycosyl acceptor, was further investi-
gated. In comparison with compound 5, the reactivity of the
4-hydroxy group in the rigid bicycloACTHNUTRGNEUNG[3.2.1] system of 7 is en-
hanced by conformational switching of the pyranosyl ring,
thereby changing the orientation of the 4-hydroxy group
from the axial to equatorial position.[15c] As summarized in
Scheme 4, benzylation of the triol 8 yielded the correspond-
ing ether 22 (96%), which was subjected to sequential ace-
tolysis (97%) and O1-deacetylation (96%) to provide the 1-
alcohol 23. Trichloroacetimidation of 23 led to the donor 6
(91%), which was coupled with the 4-alcohol 7 in the pres-
ence of TMSOTf to afford the expected a disaccharide 24
388
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2009, 4, 386 – 390