Angewandte
Communications
Chemie
Table 1: Glycosylation reactions with various glycosyl donors.
unstable even with these electron-withdrawing
groups, and decomposed upon standing at room
temperature. Fluoride 19c was even more sensitive
and fully decomposed during column chromatogra-
phy. Attempts to prepare a glycosyl trichloroaceti-
midate donor also failed owing to its extreme
instability.
Given the advantages of the n-pentenyl (Pen)
glycosyl donors reported by Fraser-Reid[10] and co-
workers and the 2-(2-propylsulfinyl)benzyl (PSB)
glycosyl donors recently developed by our group,[11]
we further prepared donors 19e and 19 f
(Scheme 5). First, direct coupling of the correspond-
ing alcohols with 1b catalyzed by CuPF6(MeCN)4
efficiently generated 21a and 22a in good yields
with high stereoselectivity. Subsequent reactions
(imine reduction, nitrogen and oxygen protection,
and, in the case of 22a, oxidation) successfully
provided 19e and 19 f.
Glycosylation reactions of donors 17, 18, and
19a–19 f were examined by coupling with acceptor
24 under the corresponding classical activation
conditions (Table 1).[12] Most of the donors, except
for 17 and 18, provided disaccharide 25 in good to
excellent yields. Interestingly, the a-anomer was
favored in all cases; almost exclusive a-selectivity
was observed for donors 19a and 19 f.[13] This
observation is in contrast to the hypothesis that
steric hindrance from the C3 substituent would lead
to b-selectivity.[14]
Entry Donor Reaction conditions
Yield a/b[b]
[%][a]
[c]
[c]
1
17
18
AuBr3 (0.2 equiv), CH3CN, RT, 24 h
Ph2SO (4.0 equiv), Tf2O (2.0 equiv), 2-chloropyr-
idine (7.5 equiv), CH2Cl2, À408C, 24 h
NIS (2.2 equiv), AgOTf (0.4 equiv), 4 ꢀ M.S.,
CH2Cl2, 08C, 1.5 h
5
5
–
–
2[d]
3[e]
19a
97
79
>20:1
4
5
19b
19c
Tf2O (2.0 equiv), 4 ꢀ M.S., CH2Cl2, À408C, 1 h.
5.8:1
8.3:1
2.8:1
BF3·OEt2 (1.0 equiv), 4 ꢀ M.S., CH2Cl2, 08C, 2.0 h 91
6[d,f] 19d
PPh3AuNTf2 (0.2 equiv), 4 ꢀ M.S., CH2Cl2, À408C, 99
1.5 h
7
8
19e
19 f
NIS (2.2 equiv), TMSOTf (0.6 equiv), CH2Cl2, 08C, 85
0.3 h
Tf2O (2.0 equiv), 4 ꢀ M.S., CH2Cl2, À408C, 1.5 h
10.6:1
82
>20:1
[a] Yield of isolated product. [b] The a/b ratio of the product after isolation. [c] The
a/b ratio was not determined. [d] Donor (1.5 equiv). [e] Activation by MeOTf or NIS/
TfOH resulted in low yields. [f] The reaction at 08C gave similar results (98%,
a/b=3:1). M.S.=molecular sieves, NIS=N-iodosuccinimide, Tf=trifluorometha-
nesulfonyl, TMS=trimethylsilyl.
29. Instead, monosaccharide 28, in which the methoxy group
has been transferred from the acceptor l-Avi-27, was isolated
in 78% yield. This result further indicated the high instability
of the 3-aminodeoxyglycosides. Next, the much milder Yu
glycosylation conditions,[12g,h] which are based on the gold-
catalyzed activation of ortho-alkynylbenzoate (Abz) glyco-
sides, were employed for the assembly of this oligosaccharide.
Fortunately, the coupling of d-Ris-30 and l-Avi-27 furnished
disaccharide 31 in 90% yield and in an a/b ratio of 8:1. The
structure of the a-anomer 31 was confirmed by single-crystal
X-ray diffraction.[16] Further removal of the acetate group in
31 and coupling with l-Ris-33 provided 34 and 35 in an
overall yield of 92% with a/b = 3:1. Interestingly, the use of
DMF as an additive reversed the selectivity in this case with
a/b = 1:4 (34/35).[17] However, coupling of trisaccharide 36
with d-Sac-37 under the same conditions failed to give the
desired product. Changing the solvent from CH2Cl2 to toluene
successfully produced tetrasaccharides 38 and 39 with an
Scheme 5. Synthesis of the 3-aminoglycosyl donors 19e and 19 f.
n-Pen-OH=4-penten-1-ol, PIFA=[bis(trifluoroacetoxy)iodo]benzene,
PTB-OH=2-(isopropylthio)benzyl alcohol.
a/b ratio of 1:3.5, albeit in a modest yield of 40%. In this case,
the yield increased to 90% with a/b = 1:1.1 when DMF was
not added.
The success in using these donors in glycosylation
reactions encouraged us to assemble a challenging tetrasac-
charide containing four different 3-aminosugar components
(l-Ris, d-Ris, l-Avi, and d-Sac; Scheme 6). However, in an
initial attempt, coupling of 4-nitrobenzensulfonate (Ns)[15]
protected thioglycoside l-Ris-26 with methyl glycoside
l-Avi-27 gave only a trace amount of the desired disaccharide
In conclusion, we have described the synthesis of a diverse
series of naturally occurring 3-amino- and 3-nitro-2,3,6-
trideoxypyranose derivatives and analogues thereof from
readily available intermediates. After transformation of these
3-aminosugars into various glycosyl donors, their glycosyla-
tion efficiencies and selectivities were investigated, and good
to excellent yields with a-selectivity were observed. Most
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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