Synthesis of l - glycero- And d - glycero- d - manno-Heptose Building Blocks for Stereoselective Assembly of the Lipopolysaccharide Core Trisaccharide of Vibrio parahemolyticus O2

Article abstract of DOI:10.1021/acs.orglett.0c02961

Synthesis of bacterial cell surface l-glycero-d-manno-heptose (l,d-Hep)- and d-glycero-d-manno-heptose (d,d-Hep)-containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the l,d-Hep an

Full text of DOI:10.1021/acs.orglett.0c02961

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Letter
Synthesis of L-glycero- and D-glycero-D-manno-Heptose Building
Blocks for Stereoselective Assembly of the Lipopolysaccharide Core
Trisaccharide of Vibrio parahemolyticus O2
Junchang Wang, Jingjing Rong, Qixin Lou, Yirong Zhu, and You Yang*
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ABSTRACT: Synthesis of bacterial cell surface L-glycero-D-manno-heptose (L,D-Hep)- and D-glycero-D-manno-heptose (D,D-Hep)-
containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the L,D-
Hep and D,D-Hep building blocks. Using L-lyxose and D-ribose as starting materials, this approach features diastereoselective
Mukaiyama-type aldol reactions as the key steps. On the basis of the synthetic L,D-Hep and D,D-Hep building blocks, we achieved the
first stereoselective synthesis of the unique α-L,D-Hep-(1→3)-α-D,D-Hep-(1→5)-α-Kdo core trisaccharide of the lipopolysaccharide
of Vibrio parahemolyticus O2.
acteria can secrete a diverse array of rare sugars that do
not exist in mammals. Among the rare sugars, higher
carbon sugars such as L-glycero-D-manno-heptose (L,D-Hep), D-
glycero-D-manno-heptose (D,D-Hep), and 3-deoxy-D-manno-oct-
these higher carbon sugars could prompt the development of
antibacterial agents, vaccine candidates, and diagnostic
tools.
B
3
,5,7,8
Synthesis of L,D-Hep and D,D-Hep building blocks often
relied on the homologation strategy by one-carbon elongation
2
-ulosonic acid (Kdo) are usually present in the inner core
2
region of the lipopolysaccharides (LPS) of Gram-negative
bacteria, while they are sometimes found in the outer core
of the mannose derivatives. The most common approaches
include Grignard addition to the C-6 aldehyde moiety of the
protected mannose derivatives, and Wittig olefination of the
1,6-dialdopyranoside substrates followed by osmium-mediated
1
−3
region and O-antigens of the LPS of bacteria (Figure 1).
Because LPS mediate a range of biological processes, including
the host−bacterium interactions, the L,D-Hep-, D,D-Hep-, and
Kdo-containing LPS fragments are required for biological
studies of inhibition of the biosynthesis of the bacterial cell
wall polysaccharides and stimulation of the immune response
9
,10
dihydroxylation or proline-catalyzed α-aminoxylation.
Occasionally, the L,D-Hep and D,D-Hep building blocks could
also be synthesized by the Corey−Chaykovsky reaction via the
11
epoxide species from the 1,6-dialdopyranoside substrates.
2
,4−6
against pathogenic bacteria.
Along this line, synthesis of
Notably, indium-mediated acyloxyallylation of unprotected L-
lyxose and D-ribose followed by ozonolysis gave access to free
12
or peracetylated L,D-Hep and D,D-Hep in a practical manner.
Received: September 4, 2020
Figure 1. Common higher carbon sugars found in the lip-
opolysaccharides and capsular polysaccharides of bacteria.
©
XXXX American Chemical Society
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Recently, Stanetty and co-workers described a technically
simple and versatile approach for the differentiation of the
multiple hydroxyl groups of the L,D-Hep and D,D-Hep
Similarly, D,D-Hep building block 3 can be prepared on a gram
scale via the Mukaiyama-type aldol reaction between suitably
protected D-ribose derivative 7 and silyl enol ether 6.
Aldehydes 5 and 7 can be obtained from commercially
available L-lyxose 8 and D-ribose 9.
The preparation of L,D-Hep building block 2 started from L-
lyxose 8 (Scheme 2). Thus, treatment of 8 with ethanethiol
1
3
backbones. Furthermore, de novo synthesis of L,D-Hep
building blocks based on the Mukaiyama-type aldol reaction
was utilized for the synthesis of LPS fragments of pathogenic
8
a,14
bacteria.
Despite the elegant synthesis of L,D-Hep and D,D-
Hep building blocks through the approaches described above,
efficient synthesis of L,D-Hep- and D,D-Hep-containing
oligosaccharides is still challenging. Here, we report a
convenient and efficient approach featuring the Mukaiyama-
type aldol reactions as the key steps to synthesize the L,D-Hep
and D,D-Hep building blocks from L-lyxose and D-ribose,
respectively. On the basis of the synthetic L,D-Hep and D,D-Hep
building blocks, we complete the stereoselective synthesis of
the unique α-L,D-Hep-(1→3)-α-D,D-Hep-(1→5)-α-Kdo core
trisaccharide 1 of the LPS of Vibrio parahemolyticus O2
Scheme 2. Synthesis of L,D-Hep Building Block 2
(
Scheme 1), which is a halophilic marine bacterium associated
15
with food poisoning from seafood.
Scheme 1. Retrosynthetic Analysis of LPS Core
Trisaccharide 1 of V. parahemolyticus O2
with the aid of hydrochloric acid and subsequent reaction with
2,2-dimethoxypropane under the promotion of pyridinium p-
toluenesulfonate afforded 4,5-O-isopropylidene-protected L-
18
lyxose derivative 10 in 83% yield over two steps. The 3-
hydroxyl group of 2,3-diol 10 was regioselectively protected
with TBSCl in the presence of imidazole in DMF to give
alcohol 11 in excellent yield (93%). The remaining 2-hydroxyl
group in 11 was benzylated with benzyl bromide and sodium
hydride in DMF, although partial migration of the TBS group
from C3 to C2 was also observed, affording compound 12 as
the major product in 76% yield. The structure of 12 was
confirmed by analysis of the NMR spectra of the 3-acetylated
derivative of 12, where the 3-TBS group was replaced with an
19
acetyl group.
Exposure of 12 to a mixed solution of NIS, DTBP, and
AgOTf in acetonitrile, acetone, and water led to the cleavage of
the dithioacetal group, providing aldehyde 5 in moderate 60%
yield. The Mukaiyama-type aldol reaction between aldehyde 5
and silyl enol ether 6 under the activation of MgBr ·OEt in
2
2
toluene and dichloromethane at −78 °C resulted in a very
clean reaction, producing the desired seven-carbon skeleton 13
2
0
in 97% yield with excellent 2,3-anti-3,4-syn-selectivity.
Treatment of 13 with trifluoroacetic acid led to a complex
mixture probably arising from the partial cleavage of the
isopropylidene and TBS groups as well as the concomitant
lactonization. Gratifyingly, exposure of 13 to HF·pyridine in
pyridine resulted in the removal of the silyl groups and
subsequent cyclization without affecting the isopropylidene
group, affording the desired lactone 14 in 76% yield.
On the basis of the structure of trisaccharide 1 that contains
an amine linker at the reducing end for subsequent conjugation
to a carrier protein or an array surface, it can be derived from
L,D-Hep building block 2, D,D-Hep building block 3, and Kdo
building block 4 (Scheme 1). The acetyl groups installed at the
O2 positions of 2 and 3 can ensure the stereoselective
construction of 1,2-trans-linked α-L,D-Hep and α-D,D-Hep
Protection of diol 14 with triethyl orthoacetate under the
catalysis of p-toluenesulfonic acid followed by lactone
16
moieties via the neighboring-group participation effect. The
L,D-Hep building block 2 can be prepared on a gram scale via
the Mukaiyama-type aldol reaction between the suitably
t
21
reduction using LiAlH(O Bu) gave the corresponding lactol.
3
Ring opening of the orthoacetate of the lactol described above
with 80% aqueous acetic acid at room temperature and
17
protected L-lyxose derivative 5 and silyl enol ether 6.
B
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subsequent acetylation produced triacetylated product 15 in
lactone 20 in 66% yield. The formation of lactones 14 and 20
in not very high yields was mainly attributed to the partial
removal of the two TBS groups under the conditions presented
here.
Lactone 20 was then converted into triacetylated product 21
in 74% yield through only one silica gel column chromatog-
8
0% yield over four steps through only one silica gel column
chromatography. The structure of the D-manno-configured
pyranose ring in 15 was unambiguously confirmed by analysis
of the H, C, and two-dimensional (2D) NMR spectra of
1
13
15α (H1, 6.07 ppm, d, J = 2.4 Hz; H2, 5.23 ppm, dd, J = 2.4,
3.6 Hz; H3, 5.34 ppm, dd, J = 3.6, 9.6 Hz; H4, 4.08 ppm, t, J =
9.6 Hz; H5, 3.69 ppm, dd, J = 2.4, 9.6 Hz). Selective cleavage
raphy step via a four-step sequence involving formation of the
t
orthoacetate, reduction of the lactone with LiAlH(O Bu) , ring
3
of the anomeric acetate in 15 with morpholine in ethyl acetate
gave the corresponding hemiacetal, which was reacted with N-
phenyl-2,2,2-trifluoroacetimidoyl chloride to afford N-phenyl
opening of the orthoacetate with 50% aqueous acetic acid, and
acetylation with acetic anhydride. The structure of the D-
manno-configured pyranose ring in 21 was also unambiguously
22
1
13
trifluoroacetimidate 2 in 88% yield over two steps.
validated by analysis of the H, C, and 2D NMR spectra of
21α (H1, 6.04 ppm, d, J = 2.4 Hz; H2, 5.25 ppm, t, J = 3.2 Hz;
H3, 5.37 ppm, dd, J = 3.6, 8.8 Hz; H4, 3.77 ppm, t, J = 9.2 Hz;
H5, 3.92 ppm, dd, J = 3.2, 9.6 Hz). Selective removal of the
anomeric acetate in 21 with morpholine followed by reaction
with N-phenyl-2,2,2-trifluoroacetimidoyl chloride to provide
N-phenyl trifluoroacetimidate 3 in 75% yield over two steps.
To demonstrate the utility of the L,D-Hep and D,D-Hep
building blocks, assembly of the unique core trisaccharide 1 of
the LPS of V. parahemolyticus O2 was carried out (Scheme 4).
In light of the convenience of this approach for the synthesis
of L,D-Hep building block 2 from L-lyxose, we adopt a similar
strategy to prepare D,D-Hep building block 3 from D-ribose 9
(Scheme 3). Thus, compound 9 was reacted with ethanethiol
Scheme 3. Synthesis of D,D-Hep Building Block 3
Scheme 4. Completion of Core Trisaccharide 1 of the LPS
of V. parahemolyticus O2
promoted by hydrochloric acid and subsequently protected
with 2,2-dimethoxypropane catalyzed by pyridinium p-
toluenesulfonate to give 4,5-O-isopropylidene-protected D-
ribose derivative 16 (85% over two steps). Protection of the
3
-hydroxyl group of 2,3-diol 16 with TBSCl gave 17 in 99%
yield, whose structure was verified by analysis of the NMR
19
spectra of the 2-levulinoylated derivative of 17. Benzylation
of compound 17 with benzyl bromide delivered 3-O-TBS-
protected 18 in 85% yield, albeit the formation of a trace
amount of 2-O-TBS-protected byproduct due to silyl-group
migration. Unexpectedly, employment of the system of NIS,
DTBP, and AgOTf for the removal of the dithioacetal group in
To our delight, TfOH (0.2 equiv)-catalyzed glycosylation of D-
glycero-D-manno-heptosyl N-phenyl trifluoroacetimidate 3 with
8a
the inert 5-hydroxyl group of Kdo acceptor 4 in dichloro-
methane at −40 °C proceeded smoothly to afford the
challenging (1→5)-linked D,D-Hep-Kdo disaccharide. Removal
of the acetyl groups of the resulting disaccharide with
potassium carbonate in methanol gave diol 22 in 67% yield
over two steps. The anomeric configuration of the newly
formed glycosidic linkage of disaccharide 22 was determined
by the coupling constant between C1 and H1 of the
1
8 led to the desired aldehyde 7 in a very low yield. After
numerous attempts, the dithioacetal group in 18 was efficiently
cleaved by iodine in the presence of sodium bicarbonate,
23
resulting in aldehyde 7 in high yield (84%). Notably, when the
optimized conditions were applied to the conversion of
dithioacetal 12 to aldehyde 5, the reaction led to a complex
mixture, indicating that the conversions were dramatically
affected by the substrate structures. To our delight, the MgBr2·
1
24
corresponding D,D-Hep residue ( J
= 169.5 Hz).
C1,H1
Although regioselective glycosylation of 2,3-syn-diols of
glycosyl acceptors might favor the formation of the (1→3)-
25
OEt -mediated Mukaiyama-type aldol reaction between
linked glycosides, TfOH-promoted glycosylation of diol 22
with N-phenyl trifluoroacetimidate 2 led to a mixture of the
(1→3)- and (1→2)-linked glycosides in 76% yield with poor
regioselectivity (1.5:1 3-O-linked glycoside:2-O-linked glyco-
2
aldehyde 7 and silyl enol ether 6 also provided the desired
seven-carbon skeleton 19 in 71% yield with excellent 2,3-anti-
3
,4-syn-selectivity. Similar to the cyclic reaction from 13 to 14,
2
6
treatment of 19 with HF·pyridine in pyridine gave the desired
side ratio). Thus, treatment of diol 22 with triethyl
C
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orthoacetate in the presence of p-toluenesulfonic acid
generated the cyclic orthoacetate, which was subjected to
selective ring opening of the resulting orthoacetate with 50%
aqueous acetic acid to produce 3-hydroxyl disaccharide
acceptor 23 (72% over two steps).
Coupling of disaccharide acceptor 23 with L-glycero-D-
manno-heptosyl N-phenyl trifluoroacetimidate 2 under the
catalysis of TfOH (0.1 equiv) in dichloromethane at −40 °C
afforded exclusively α-linked L,D-Hep-D,D-Hep-Kdo trisacchar-
ide 24 as the single product in 72% yield. The desired
configuration of trisaccharide 24 was confirmed by the
Qixin Lou − Shanghai Key Laboratory of New Drug Design,
School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China
Yirong Zhu − Shanghai Key Laboratory of New Drug Design,
School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02961
Notes
The authors declare no competing financial interest.
coupling constants between C1 and H1 of the corresponding
1
L,D-Hep and D,D-Hep residues ( J
= 172.5 and 174.5 Hz,
C1,H1
ACKNOWLEDGMENTS
respectively). Cleavage of the three isopropylidene groups in
4 with 80% aqueous acetic acid at 70 °C was followed by
■
2
Financial support from the National Natural Science
Foundation of China (21871081 and 22071054) and the
Fundamental Research Funds for the Central Universities
(50321031916002 and 22221818014) is gratefully acknowl-
edged.
removal of all ester groups with potassium carbonate in
methanol and then aqueous sodium hydroxide. Finally,
hydrogenolysis of the benzyl and benzyloxycarbonyl groups
over Pd(OH) /C in methanol, water, and acetic acid furnished
2
target trisaccharide 1 of the LPS of V. parahemolyticus O2 in
6
2% yield over four steps. The structure of trisaccharide 1 was
REFERENCES
■
unambiguously confirmed by a combination of spectroscopic
analysis (NMR and MS).
(
1) Holst, O. In Structure of the Lipopolysaccharide Core Region in
Bacterial Lipopolysaccharide; Knirel, Y. A., Valvano, M. A., Eds.;
19
In conclusion, we have developed a convenient and efficient
approach for the synthesis of the L,D-Hep and D,D-Hep building
blocks from L-lyxose and D-ribose, respectively, enabling the
first stereoselective synthesis of the unique LPS core
trisaccharide of V. parahemolyticus O2. The synthesis of the
L,D-Hep and D,D-Hep building blocks featured the diaster-
eoselective Mukaiyama-type aldol reactions of L-lyxose and D-
ribose derivatives with the silyl enol ether as key steps. By
employing the synthetic L,D-Hep and D,D-Hep building blocks
as synthons, we furnished the facile and stereosective synthesis
of the unique α-L,D-Hep-(1→3)-α-D,D-Hep-(1→5)-α-Kdo core
trisaccharide of the lipopolysaccharide of V. parahemolyticus
O2. This approach for the preparation of L,D-Hep and D,D-Hep
building blocks may find further application in the synthesis of
diverse LPS fragments of Gram-negative bacteria.
Springer-Verlag: Vienna, 2011.
(2) (a) Kosma, P. Curr. Org. Chem. 2008, 12, 1021−1039.
(b) Zamyatina, A.; Gronow, S.; Puchberger, M.; Graziani, A.;
Hofinger, A.; Kosma, P. Carbohydr. Res. 2003, 338, 2571−2589.
(3) (a) Cipolla, L.; Gabrielli, L.; Bini, D.; Russo, L.; Shaikh, N. Nat.
Prod. Rep. 2010, 27, 1618−1629. (b) Raetz, C. R. H.; Whitfield, C.
Annu. Rev. Biochem. 2002, 71, 635−700. (c) Angata, T.; Varki, A.
Chem. Rev. 2002, 102, 439−469.
(4) Brade, H.; Opal, S. M.; Vogel, S. N.; Morrison, D. C. Endotoxin
in Health and Disease; Marcel Dekker: New York, 1999.
5) Wright, G. D.; Sutherland, A. D. Trends Mol. Med. 2007, 13,
(
260−267.
(6) (a) Holst, O. FEMS Microbiol. Lett. 2007, 271, 3−11.
(b) Gronow, S.; Brade, H. J. Endotoxin Res. 2001, 7, 3−23.
(c) Beutler, B.; Rietschel, E. T. Nat. Rev. Immunol. 2003, 3, 169−
1
76. (d) Bryant, C. E.; Spring, D. R.; Gangloff, M.; Gay, N. J. Nat.
Rev. Microbiol. 2010, 8, 8−14.
7) (a) Bernlind, C.; Oscarson, S. J. Org. Chem. 1998, 63, 7780−
7788. (b) Crich, D.; Banerjee, A. J. Am. Chem. Soc. 2006, 128, 8078−
086. (c) Jaipuri, F. A.; Collet, B. Y. M.; Pohl, N. L. Angew. Chem., Int.
(
ASSOCIATED CONTENT
sı Supporting Information
■
8
*
Ed. 2008, 47, 1707−1710. (d) Kong, L.; Vijayakrishnan, B.; Kowarik,
M.; Park, J.; Zakharova, A. N.; Neiwert, L.; Faridmoayer, A.; Davis, B.
G. Nat. Chem. 2016, 8, 242−249.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02961.
(
8) (a) Yang, Y.; Martin, C. E.; Seeberger, P. H. Chem. Sci. 2012, 3,
Experimental procedures, characterization data, and
NMR spectra (PDF)
8
96−899. (b) Yang, Y.; Oishi, S.; Martin, C. E.; Seeberger, P. H. J.
Am. Chem. Soc. 2013, 135, 6262−6271. (c) Anish, C.; Guo, X.;
Wahlbrink, A.; Seeberger, P. H. Angew. Chem., Int. Ed. 2013, 52,
9
524−9528. (d) Reinhardt, A.; Yang, Y.; Claus, H.; Pereira, C. L.;
Cox, A. D.; Vogel, U.; Anish, C.; Seeberger, P. H. Chem. Biol. 2015,
2, 38−49.
9) (a) Dziewiszek, K.; Zamojski, A. Carbohydr. Res. 1986, 150,
63−171. (b) Dziewiszek, K.; Banaszek, A.; Zamojski, A. Tetrahedron
AUTHOR INFORMATION
■
2
(
Corresponding Author
You Yang − Shanghai Key Laboratory of New Drug Design,
School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China; orcid.org/0000-
1
Lett. 1987, 28, 1569−1572. (c) Boons, G. J. P. H.; van der Klein, P. A.
M.; van der Marel, G. A.; van Boom, J. H. Recl. Trav. Chim. Pays-Bas.
1988, 107, 507−508. (d) Bernlind, C.; Bennett, S.; Oscarson, S.
Tetrahedron: Asymmetry 2000, 11, 481−492. (e) Kim, M.; Grzeszczyk,
B.; Zamojski, A. Tetrahedron 2000, 56, 9319−9337. (f) Tikad, A.;
Vincent, S. P. in Modern Synthetic Methods in Carbohydrate Chemistry;
Vidal, S., Werz, D., Eds.; Wiley-VCH, 2014.
0
003-4438-2162; Email: yangyou@ecust.edu.cn
Authors
Junchang Wang − Shanghai Key Laboratory of New Drug
Design, School of Pharmacy, East China University of Science
and Technology, Shanghai 200237, China
Jingjing Rong − Shanghai Key Laboratory of New Drug Design,
School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China
(
10) (a) Brimacombe, J. S.; Kabir, A. K. M. S. Carbohydr. Res. 1986,
52, 329−334. (b) Jorgensen, M.; Iversen, E. H.; Madsen, R. J. Org.
1
Chem. 2001, 66, 4625−4629. (c) Crich, D.; Banerjee, A. Org. Lett.
2005, 7, 1395−1398. (d) Dohi, H.; Perion, R.; Durka, M.; Bosco, M.;
Roue, Y.; Moreau, F.; Grizot, S.; Ducruix, A.; Escaich, S.; Vincent, S.
D
https://dx.doi.org/10.1021/acs.orglett.0c02961
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
P. Chem. - Eur. J. 2008, 14, 9530−9539. (e) Stanetty, C.; Walter, M.;
Kosma, P. J. Org. Chem. 2014, 79, 582−598. (f) Mulani, S. K.; Cheng,
K.-C.; Mong, K.-K. T. Org. Lett. 2015, 17, 5536−5539. (g) Li, T.;
Tikad, A.; Durka, M.; Pan, W.; Vincent, S. P. Carbohydr. Res. 2016,
4
32, 71−75. (h) Wang, P.; Huo, C.-x.; Lang, S.; Caution, K.; Nick, S.
T.; Dubey, P.; Deora, R.; Huang, X. Angew. Chem., Int. Ed. 2020, 59,
451−6458. (i) Tian, G.; Hu, J.; Qin, C.; Li, L.; Zou, X.; Cai, J.;
Seeberger, P. H.; Yin, J. Angew. Chem., Int. Ed. 2020, 59, 13362−
3370.
11) Inuki, S.; Aiba, T.; Kawakami, S.; Akiyama, T.; Inoue, J.-i.;
Fujimoto, Y. Org. Lett. 2017, 19, 3079−3082.
6
1
(
(
12) (a) Palmelund, A.; Madsen, R. J. Org. Chem. 2005, 70, 8248−
8251. (b) Stanetty, C.; Baxendale, I. R. Eur. J. Org. Chem. 2015, 2015,
718−2726.
2
(
13) Suster, C.; Baxendale, I. R.; Mihovilovic, M. D.; Stanetty, C.
Front. Chem. 2020, 8, 625.
14) Ohara, T.; Adibekian, A.; Esposito, D.; Stallforth, P.; Seeberger,
P. H. Chem. Commun. 2010, 46, 4106−4108.
15) Hashii, N.; Isshiki, Y.; Iguchi, T.; Kondo, S. Carbohydr. Res.
003, 338, 1063−1071.
16) Yang, Y.; Zhang, X.; Yu, B. Nat. Prod. Rep. 2015, 32, 1331−
355.
(
(
2
(
1
(
(
17) Hattori, K.; Yamamoto, H. J. Org. Chem. 1993, 58, 5301−5303.
18) (a) van Delft, F. L.; Rob, A.; Valentijn, P. M.; van der Marel, G.
A.; van Boom, J. H. J. Carbohydr. Chem. 1999, 18, 165−190.
b) Chen, Y.; Wang, X.; Wang, J.; Yang, Y. Beilstein J. Org. Chem.
017, 13, 795−799.
19) See the Supporting Information for details.
20) (a) Adibekian, A.; Bindschadler, P.; Timmer, M. S. M.; Noti,
C.; Schutzenmeister, N.; Seeberger, P. H. Chem. - Eur. J. 2007, 13,
510−4522. (b) Timmer, M. S. M.; Adibekian, A.; Seeberger, P. H.
Angew. Chem., Int. Ed. 2005, 44, 7605−7607.
21) Huffman, M. A.; Smitrovich, J. H.; Rosen, J. D.; Boice, G. N.;
Qu, C.; Nelson, T. D.; McNamara, J. M. J. Org. Chem. 2005, 70,
409−4413.
22) (a) Yu, B.; Tao, H. Tetrahedron Lett. 2001, 42, 2405−2407.
b) Yu, B.; Sun, J. Chem. Commun. 2010, 46, 4668−4679.
23) Bender, M.; Mouritsen, H.; Christoffers, J. Beilstein J. Org.
Chem. 2016, 12, 912−917.
24) (a) Bock, K.; Pedersen, C. J. Chem. Soc., Perkin Trans. 2 1974,
, 293−299. (b) Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321−8348.
25) (a) Kalikanda, J.; Li, Z. Tetrahedron Lett. 2010, 51, 1550−1553.
b) Chen, L.; Kong, F. Carbohydr. Res. 2003, 338, 2169−2175.
26) (a) Mori, M.; Ito, Y.; Ogawa, T. Carbohydr. Res. 1990, 195,
99−224. (b) Utille, J.-P.; Priem, B. Carbohydr. Res. 2000, 329, 431−
39.
(
2
(
(
̈
̈
4
(
4
(
(
(
(
2
(
(
(
1
4
E
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