Organic Letters
Letter
ORCID
Ph3PAuOTf (0.2 equiv) and TfOH (0.2 equiv) as promoter
afforded the α-(1→6)-dimannoside 25 in 83% yield, which was
subjected to the removal of the TBDPS group using HF·pyridine
to provide disaccharide acceptor 26 in 98% yield. On the other
hand, thioglycoside 25 was converted into glycosyl ynenoate 27
in 81% yield over two steps via the activation of 25 with 2b using
NIS and TfOH and subsequent Sonogashira coupling with 1-
hexyne. With ynenoate 27 (1.3 equiv) and acceptor 26 (1 equiv)
as the coupling partners, repetition of the similar reaction
sequence for three times provided the 16mer polymannosyl
ynenoate 36 and the 16mer polymannoside acceptor 35 in a
highly efficient and convergent manner (glycosylation yields
91% for tetrasaccharide 28, 71% for octasaccharide 31, 67% for
hexadecasaccharide 34). The [16 + 16] coupling of ynenoate 36
(2 equiv) with acceptor 35 (1 equiv) promoted by Ph3PAuOTf
(1.0 equiv) and TfOH (0.2 equiv) in toluene furnished the α-
(1→6)-linked 32mer polymannoside 37 in 76% yield. Given
that a linker could be installed at the reducing end of 37 for
further conjugation to carrier proteins and array surfaces,
compound 37 (1 equiv) was coupled with N-benzyl-N-
benzyloxycarbonyl pentyl linker 38 (1.5 equiv) under the
activation of IBr and AgOTf to provide the 32mer polymanno-
side 39 in 74% yield. Global deprotection of 39 involving
removal of the TBDPS group with HF·pyridine, saponification
of the 32 benzoyl groups with sodium methoxide in methanol
and dichloromethane, and hydrogenolysis of the 65 benzyl and
one benzyloxycarbonyl groups over Pd/C in THF and water
furnished the target 32mer polymannoside 40 in 71% yield over
three steps.
In conclusion, we have developed a simple and versatile
gold(I)-catalyzed glycosylation with glycosyl ynenoates as
donors for the synthesis of a variety of oligo- and
polysaccharides. Structurally, the glycosyl ynenoate donors
described here are relatively simple and atom-economical due to
the absence of the fused benzene ring. Moreover, the stable
glycosyl ynenoate donors can be easily prepared from various
precursors such as sugar lactols and thioglycosides. The present
glycosylation protocol with glycosyl ynenoates as donors under
the catalysis of gold(I) complex with or without the aid of TfOH
was found to possess a very wide substrate scope as exemplified
in the efficient synthesis of ST3 tetrasaccharide and the 32mer
polymannoside. In combination with the glycosyl trichloroimi-
date and the thioglycoside, the glycosyl ynenoate proved to be
an effective donor in the multiple orthogonal one-pot synthesis
of the tetrasaccharide. Additionally, the glycosyl ynenoates have
found application in the latent-active synthesis of oligosacchar-
ides. With the simplicity and versatility as promising properties,
we believe this new glycosylation method shall find wide
application in the synthesis of a diverse class of glycans and
glycoconjugates.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support from the National Thousand Young Talents
Program (Y100-4Q-1701, YC0140103), the National Natural
Science Foundation of China (21871081), and the Fundamental
Research Funds for the Central Universities (50321031916002,
22221818014) is gratefully acknowledged.
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AUTHOR INFORMATION
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Corresponding Author
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Org. Lett. XXXX, XXX, XXX−XXX