Synthesis of the hyper-branched core tetrasaccharide motif of chloroviruses

Article abstract of DOI:10.1039/d0ob02176h

Chemical synthesis of complex oligosaccharides, especially those possessing hyper-branched structures with one or multiple 1,2-cisglycosidic bonds, is a challenging task. Complementary reactivity of glycosyl donors and acceptors and proper tuning of the s

Full text of DOI:10.1039/d0ob02176h

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Synthesis of the hyper-branched core
tetrasaccharide motif of chloroviruses†
Cite this: Org. Biomol. Chem., 2021,
19, 1315
Bijoyananda Mishra, Sujit Manmode, Gulab Walke, Saptashwa Chakraborty,
Mahesh Neralkar and Srinivas Hotha
*
Chemical synthesis of complex oligosaccharides, especially those possessing hyper-branched structures
with one or multiple 1,2-cis glycosidic bonds, is a challenging task. Complementary reactivity of glycosyl
donors and acceptors and proper tuning of the solvent/temperature/activator coupled with compromised
glycosylation yields for sterically congested glycosyl acceptors are among several factors that make such
syntheses daunting. Herein, we report the synthesis of a semi-conserved hyper-branched core tetrasac-
charide motif from chloroviruses which are associated with reduced cognitive function in humans as well
as in mouse models. The target tetrasaccharide contains four different sugar residues in which L-fucose is
connected to D-xylose and L-rhamnose via a 1,2-trans glycosidic bond, whereas with the D-galactose
residue is connected through a 1,2-cis glycosidic bond. A thorough and comprehensive study of various
accountable factors enabled us to install a 1,2-cis galactopyranosidic linkage in a stereoselective fashion
under [Au]/[Ag]-catalyzed glycosidation conditions en route to the target tetrasaccharide motif in 14
steps.
Received 1st November 2020,
Accepted 4th January 2021
DOI: 10.1039/d0ob02176h
rsc.li/obc
machinery and the role of their capsid glycoproteins in host
infections, particularly for cross kingdom infection, though
1. Introduction
Chlorella viruses or Chloroviruses (CV) are plaque forming very rare, is in high demand and for that accessibility of
viruses which are present in freshwater throughout the world various natural and synthetic analogues is essential.
and infect certain unicellular, eukaryotic, chlorella-like green
Slight structural variation in glycan structures is exhibited
algae, also called Zoochlorellae.1a–e These are large, icosahe- by different types of Chloroviruses;4 yet, structural analysis of
dral (190 nm in diameter), dsDNA-containing viruses with an N-linked glycans showed a common core region.4c The core
internal lipid membrane.1f–g One of the most important fea- motif contains a hyper-branched fucose unit at the center, two
tures these chloroviruses possess is the ability to use their own xylose units (one proximal and one distal xylose), one terminal
glycosylation machinery to encode most, if not all, of the com- galactose unit, and one glucose unit at the reducing end which
ponents involved in manipulating carbohydrates.1d–g,2a The is further attached to the asparagine (Asn) moiety of major
presence of Chlorovirus ATCV-1 in human oropharyngeal capsid proteins and a semi-conserved rhamnose (D- or L-) unit
virome, and its association with statistically significant decline 1.4c Although the configuration of the rhamnose residue is
of cognitive assessments, visual processing and motor speed highly species dependent, yet, the majority of species contain
in humans and mouse models2b,c put these in the limelight. the L-isomer along with methylation at the O-3 position
Green microalgae are a promising resource for the large-scale (Fig. 1).4d
production of high value-added proteins,3a–c biofuels and bio-
materials.3d In addition, there is growing interest to use micro-
algae as potentially attractive cell factories for biopharmaceuti-
2. Results and discussion
cal production.3e Therefore, viral infection of these green
microalgae could severely impact the biopharmaceutical and
food industries. Hence, a detailed study of their glycosylation
The first synthesis of the core hexasaccharide with three –OMe
groups from the ATCV-1 species was accomplished by Lin
et al.5a and subsequently Wang et al.5b reported the synthesis
of a hexasaccharide and quite recently, a nonasaccharide was
reported by Lin et al.5c Structural complexity coupled with
strong biological significance and our continued interest in
utilizing silver-assisted gold-catalyzed glycosylations6a for bio-
conjugates encouraged us to investigate the synthesis of hyper-
Department of Chemistry, Indian Institute of Science Education and Research, Pune –
411 008, MH, India. E-mail: s.hotha@iiserpune.ac.in; http://www.iiserpune.ac.in/~s.
hotha; Tel: +91 20 25908015
†Electronic supplementary information (ESI) available: Spectral charts for all
new compounds. See DOI: 10.1039/d0ob02176h
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1315

View Article Online
Paper
Organic & Biomolecular Chemistry
of fucoside 9 at the C4 position with TBDMSCl/imidazole in
DMF, followed by deprotection of the acetyl group from the C3
position under Zemplén conditions, and subsequent conver-
sion to levulinoate using levulinic acid/DIC/DMAP gave fuco-
side 10. Finally, fluoride-mediated cleavage of the silyl ether
afforded the required aglycon 3 in 96% yield (Scheme 1).
The synthesis of building block 4 was initiated by the acid-
catalyzed reaction of D-xylose with allyl alcohol at 80 °C for 6 h
followed by benzoylation using BzCl/py/DMAP to produce the
allyl 2,3,4-tri-O-benzoyl xylopyranoside 11 as an α/β mixture in
76% yield. Subsequent Pd-mediated hydrolysis of xyloside 11
released the anomeric position, and the reaction with the
easily available ethynylcyclohexyl (4-nitrophenyl) carbonate
12 6a in the presence of DMAP afforded the xylopyranosyl
alkynyl carbonate donor 4 in 85% yield (Scheme 2).
Fig. 1 Structure of N-linked hexasaccharide 1 of ATCV-1, targeted tet-
rasaccharide 2 and the list of the required monosaccharide building
blocks (3–6).
The preparation of building block 5 was initiated by react-
ing L-rhamnose with allyl alcohol in the presence of a catalytic
amount of CSA at 80 °C for 6 h followed by acetonide protec-
tion using 2,2-dimethoxy propane and a catalytic amount of
PTSA in DMF produced the acetonide protected α-allyl rham-
nopyranoside 13 as a major product. C4-O-Benzylation of the
rhamnoside 13 using BnBr/NaH/TBAI in DMF afforded the
benzyl ether 14 that upon hydrolysis of the acetonide under
acidic conditions at 55 °C resulted in a diol. The diol was sub-
jected to stannylene-mediated regioselective methylation using
MeI/TBAI/Bu2SnO in toluene at 105 °C giving the allyl rhamno-
side 15 in 68% yield over two steps. Furthermore, compound
15 was benzoylated and hydrolysis of the allyl moiety afforded
a hemiacetal that was directly taken for the next reaction with
easily available ethynylcyclohexyl (4-nitrophenyl) carbonate 12
in the presence of DMAP to afford the desired rhamnosyl
alkynyl carbonate donor 5 in 82% yield (Scheme 3).
branched tetrasaccharide motif 2 having only one –OMe group
on L-rhap (Fig. 1).4c
The retrosynthetic analysis of the target hyper-branched tet-
rasaccharide 2 was hypothesized considering all the salient
features of [Au]/[Ag]-catalyzed alkynyl carbonate donor chemis-
try6a envisioning that it can be synthesized from four building
blocks 3, 4, 5 and 6 (Fig. 1). Tetrasaccharide 2 contains two
1,2-trans and one 1,2-cis glycosidic linkages. The formation of
the 1,2-trans glycosidic bond (for installation of xylp- and
rhap-) using the [Au]/[Ag]-catalyzed glycosylation protocol can
be accomplished by invoking neighboring group participation
from the C2-esters. With a limited number of possibilities for
the central fucose residue, orthogonally cleavable C-3 levulino-
ate was considered.
Installation of 1,2-cis galactopyranose under mild con-
ditions is challenging. Previous reports suggest that 4,6-di-tbu-
tyl silyl protection7a or an ester7b–e at the C-4 position offers
α-predominant galactopyranosides. However, the use of the
tbutyl silyl moiety was not considered as it might be suscep-
tible to cleavage under the glycosidation conditions. Hence, a
detailed study about the influence of protecting groups was
performed to obtain α-galactopyranosides.
Our synthetic endeavor commenced with the synthesis of
the central L-fucose acceptor 3. L-Fucose was treated with allyl
alcohol and a catalytic amount of CSA at 80 °C for 6 h, fol-
lowed by isopropylidenation using 2,2-dimethoxy propane and
a catalytic amount of PTSA in DMF at 25 °C for 4 h, which
afforded the protected allyl fucoside as an α/β mixture from
which α-allyl fucoside 7 was isolated as a major product in
75% yield over two steps.
The lone C2-OH of acetonide 7 was protected as a p-methox-
ybenzyl ether using PMBCl/NaH/DMF in 94% yield.
Subsequent hydrolysis of acetonide 8 using 80% AcOH in
H2O–THF at 55 °C followed by the regioselective acetylation at
the C3 position using AcCl/py at 0 °C afforded the desired allyl
fucoside 9 in 78% yield over two steps. Furthermore, silylation
Scheme 1 Synthesis of central L-fucose acceptor 3.
1316 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
Scheme 2 Synthesis of D-xylose carbonate donor 4.
Scheme 4 Synthesis of various galactopyranosyl carbonate donors.
Reagents: (a) Allyl alcohol, AcCl, 80 °C, 6 h, 85%; (b) PhCH(OMe)2, PTSA,
DMF, 60 °C, 4 h, 90%; (c) 2.5 equiv. BnBr, NaH, TBAI, DMF, 0–25 °C, 5 h,
94% for 16 and 96% for 6a; (d) PTSA, CH2Cl2–MeOH (1 : 1), 25 °C, 2 h,
96%; (e) PdCl2, CH2Cl2–MeOH (1 : 3), 25 °C, 3 h, 96% for 6a, 94% for 6b,
92% for 6c, 95% for 6d, 93% for 6e, 92% for 6f and 94% for 6g respect-
ively; (f) 1-ethynylcyclohexyl (4-nitrophenyl) carbonate (12), DMAP,
CH2Cl2, 25 °C, 3 h, 95% for 6a, 93% for 6b, 94% for 6c, 92% for 6d, 95%
for 6e, 96% for 6f and 93% for 6g respectively; (g) 3 equiv. NapBr, NaH,
TBAI, DMF, 0–25 °C, 12 h, 86%; (h) AcCl, pyridine, DMAP, 0–25 °C, 4 h,
94% for 6c, 96% for 6e, 95% for 6f, 92% for 6g; (i) BzCl, pyridine, DMAP,
0–25 °C, 6 h, 96%; ( j) 1.2 equiv. BnBr, NaH, TBAI, DMF, 0–10 °C, 5 h,
78%; (k) 1.5 equiv. NapBr, NaH, TBAI, DMF, 0–25 °C, 12 h, 80%; (l)
TBDPS-Cl, imidazole, DMF, 0–25 °C, 4 h, 90%.
DMF and BnBr or NapBr respectively to obtain dibenzyl or
dinapthyl ethers whereas diacylate and dibenzoate were
obtained by the treatment of the corresponding acyl halides
in pyridine. Subsequently, all four compounds were subjected
to the deprotection of the allyl moiety and converted to the
alkynyl carbonates 6a–6d under the aforementioned reaction
conditions (Scheme 4). In parallel, regioselective protection
of the primary C-6 hydroxyl group was effected using NaH/
BnBr or NapBr at 0 °C; acetylation using AcCl in pyridine fol-
lowed by the hydrolysis of the allyl ether under Pd-catalysed
Scheme 3 Synthesis of L-rhamnose carbonate donor 5.
One of the most challenging aspects in the synthesis of tet- conditions and subsequent conversion to the corresponding
rasaccharide 2 is the installation of the 1,2-cis galactopyranosi- carbonates using carbonate reagent 12 afforded the desired
dic linkage for which a thorough investigation was required. In donors 6e and 6f. Silyl ether formation, acetylation and sub-
this direction, several substituted galactosides 6a–6g which are sequent conversion of allyl glycoside to the glycosyl carbonate
easily synthesized from a common precursor 16 6b were envi- resulted in the donor 6g.
sioned (Scheme 4).
For the synthesis of all envisaged galactopyranosyl donors
Two sets of compounds were envisaged, viz. one set con- 6a–6g, the investigation on the α-stereoselective galactopyrano-
tained all protecting groups are same whereas the second set sylation commenced with the standard [Au]/[Ag]-catalysed gly-
had two orthogonally cleavable protecting groups at the C-4,6 cosidation reaction between the glycosyl donor 6a and the
positions. Accordingly, diol 16 was first treated with NaH/ model aglycon glucose derivative 17 6a as substrates. Earlier
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1317

View Article Online
Paper
Organic & Biomolecular Chemistry
research efforts have shown the formation of 1,2-cis galactopyr- outcome does not alter much (entries 12–15) and hence, gold-
anosides when 1,2-trans galactosyl donors were utilized.7–13
phosphite 18a was considered for further experiments. The
Accordingly, the anomeric α- and β-isomers of the donor 6a best optimized conditions were found to be 10 mol% each of
were separated as 6aα and 6aβ and individually subjected to Au-phosphite 18a and AgOTf as catalysts, chlorobenzene as the
the standard [Au]/[Ag]-catalytic conditions to obtain an anome- solvent system at 25 °C in the presence of 4 Å MS powder.
ric mixture (3.5 : 1.0 α : β) irrespective of the stereochemical
In continuation, other galactosyl carbonates (6b–6g) were
identity of the starting 6aα or 6aβ; in addition, the anomeric investigated under the aforementioned conditions using car-
mixture of donor 6a also yielded the same 3.5 : 1.0 (α : β) bonates 6b–6g as donors and alcohol 17 as the aglycon in the
mixture of galactopyranosides 19 and thus further screening presence of 10 mol% each of Au-phosphite 18a and AgOTf in
experiments were conducted with anomeric mixtures only chlorobenzene at 25 °C (Table 2). Switching the benzyl ethers
(Table 1). Conducting the galactosylation between 6a and 17 at C-4,6 to Nap-ethers as in donor 6b or acetates as in donor 6c
with standard gold-phosphite catalyst 18a in CH3CN dimin- resulted in the enhancement of the α : β ratio to 12.0 : 1.0 and
ished the yield as well as reversed the stereoselectivity (entry 2, 16.0 : 1.0 respectively (entries 1 and 2, Table 2) whereas the
Table 1) whereas no reaction was noticed when the reaction dibenzoate donor 6d produced pure 1,2-cis or α-galactoside in
was conducted in THF or 1,4-dioxane (entries 3 and 4, 95% yield which may be due to the long range participation of
Table 1). The anomeric α : β ratio reduced from 3.5 : 1.0 in the acylate from the C-4 position as evidenced by earlier
CH2Cl2 to 2.0 : 1.0 in toluene (entry 5) and luckily, chloroben- investigators.7–13 However, we need orthogonally cleavable pro-
zene afforded an α : β ratio of 8.0 : 1.0 (entry 6) and that of a tecting groups at the C-4 and C-6 positions and hence, donors
reaction in bromobenzene showed 10.0 : 1.0 selectivity (entry 7, 6e–6g were studied. Donors 6e and 6f produced anomeric mix-
Table 1). However, the higher boiling point of bromobenzene tures whereas donor 6g afforded pure α-selectivity in an excel-
discouraged us from using it in further reactions. Temperature lent yield.
is yet another factor that influences the stereochemical
outcome in the majority of glycosidations.
The successful synthesis of all building blocks and identifi-
cation of conditions for the stereoselective installation of
Entries 8–11 clearly demonstrate that the best galactopyranoside residues encouraged us to advance the syn-
α-stereoselectivity can be conveniently obtained when the reac- thesis of hyper-branched tetrasaccharide motif 2. Accordingly,
tions are conducted at 25 °C. In continuation, we also varied the synthesis of hyper-branched tetrasaccharide motif 2 com-
the gold catalysts 18b–e and noticed that the stereochemical menced with the preparation of disaccharide 20 from the
xylose carbonate donor 4 and fucose acceptor 3 prepared vide
supra in the presence of 10 mol% each of Au-phosphite 18a
and AgOTf in CH2Cl2 at 25 °C with 98% yield. In the 13C NMR
Table 1 Optimization for stereoselective 1,2-cis galactopyranosidic
spectrum of compound 20, the appearance of two anomeric
carbons at δ 96.2 ppm revealed the presence of two inter-glyco-
sidic linkages and was further confirmed by HRMS analysis,
m/z calculated for C48H50O15Na+, [M + Na]+: 889.3047; found:
889.3042.
linkage formation
Disaccharide 20 is interesting due to the presence of PMB-
ether and levulinoates as they are orthogonal to each other
which in turn can be orthogonally cleaved off without affecting
the benzoates present on the xylopyranoside moiety.
Accordingly, the treatment of disaccharide with DDQ in moist
dichloromethane at 25 °C afforded the aglycon 21 which was
coupled with the galactopyranosyl donor 6g using 10 mol%
each of Au-catalyst 18a and AgOTf in chlorobenzene at 25 °C to
Entry
Au-catalyst
Solvent
T (°C)
Yield (%)
α : β ratio
1
2
3
4
5
6
7
8
18a
18a
18a
18a
18a
18a
18a
18a
18a
18a
18a
18b
18c
18d
18e
CH2Cl2
CH3CN
THF
25
25
25
25
25
25
25
45
−40
45
−40
25
25
25
25
98
20
0
3.5 : 1.0
1.0 : 2.0
—
Table 2 Effect of protecting groups on 1,2-cis galactopyranosidic bond
formation
1,4-Dioxane
Toluene
C6H5Cl
C6H5Br
CH2Cl2
CH2Cl2
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
0
—
85
95
89
98
80
80
80
90
87
75
98
2.0 : 1.0
8.0 : 1.0
10.0 : 1.0
3.0 : 1.0
2.0 : 1.0
8.0 : 1.0
2.0 : 1.0
8.5 : 1.0
8.5 : 1.0
8.0 : 1.0
8.0 : 1.0
Entry
Glycosyl donor
Aglycon
α : β ratio
Yield (%)
1
2
3
4
5
6
6b
6c
6d
6e
6f
17
17
17
17
17
17
12.0 : 1.0
16.0 : 1.0
Pure α
15.0 : 1.0
20.0 : 1.0
Pure α
93
96
95
93
94
98
9
10
11
12
13
14
15
6g
Reaction conditions: Gold-phosphite (18a) (10 mol%), AgOTf
(10 mol%), C6H5Cl, 25 °C, 4 Å MS powder, 1 h.
1318 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
afford trisaccharide 22 in 95% yield. Gratifyingly, the galactosy- further subjected to [Au]/[Ag]-assisted glycosylation with rham-
lation occurred to produce 1,2-cis or α-galactoside only nose carbonate donor 5 in the presence of 10 mol% each of
(Scheme 5). The 13C NMR spectrum of trisaccharide 22 was Au-catalyst 18a and AgOTf in CH2Cl2 producing the desired tet-
1
confirmed due to the presence of two 1,2-trans anomeric rasaccharide 2 in 91% yield (Scheme 5). In the H NMR spec-
carbons at δ 96.5 and 100.5 ppm corresponding to the fucp- trum of tetrasaccharide 2, resonances from most of the anome-
and xylp- residues respectively, whilst the characteristic 1,2-cis ric protons overlapped with that of sugar ring protons and
anomeric carbon for the galp- residue was noticed at δ hence, the structural homogeneity was obtained from the 13C
98.1 ppm.14 Furthermore, trisaccharide 22 was confirmed by NMR and mass spectral studies. In the 13C NMR spectrum of
HRMS analysis, m/z calculated for C78H84O20SiNa+, [M + Na]+: tetrasaccharide 2, the appearance of an additional anomeric
1391.5223; found: 1391.5220.
carbon at δ 99.9 ppm for rhap- along with other three anome-
Subsequent deprotection of the levulinyl ester of tri- ric carbons at δ 98.1, 98.8 and 101.2 ppm showed the presence
saccharide 22 using hydrazine hydrate afforded the corres- of four inter-glycosidic linkages in tetrasaccharide 2.14 In
ponding trisaccharide alcohol 23 in 86% yield, which was addition, tetrasaccharide 2 was confirmed by HRMS analysis,
m/z calculated for C94H100O23SiNa+, [M + Na]+: 1648.6356;
found: 1648.6351.
On the other hand, tetrasaccharide 2 can be obtained by
another route from disaccharide 20. Accordingly, disaccharide
20 was treated with NH2NH2·H2O to deprotect the levulinoate
which resulted in the formation of aglycon 24 in 90% yield.
Furthermore, aglycon 24 was reacted with rhamnose carbonate
donor 5 in the presence of 10 mol% each of Au-catalyst 18a
and AgOTf to afford trisaccharide 25 in 97% yield (Scheme 5).
In the 13C NMR spectrum, three anomeric carbons were
observed at δ 96.0, 98.4 and 99.7 ppm and the characteristic
resonances due to four benzoyl groups appeared at δ 165.0,
165.5, 165.6 and 166.2 ppm. In addition, trisaccharide 25 was
further confirmed by HRMS analysis, m/z calculated for
C64H66O18SiNa+, [M + Na]+: 1145.4147; found: 1145.4139.
In continuation, the deprotection of the PMB-ether using
DDQ converted trisaccharide 25 to the corresponding aglycon
26 in 88% yield, which upon subsequent glycosidation with
rhamnose carbonate donor 5 in the presence of 10 mol% each
of Au-catalyst 18a and AgOTf in chlorobenzene at 25 °C for
1 hour afforded the corresponding tetrasaccharide 2 in 94%
yield along with 100% α-selectivity (Scheme 5). The perfect
matching of NMR and the molecular weight of the tetrasac-
charide synthesized by two alternative routes strongly con-
firmed the successful synthesis of tetrasaccharide 2.
3. Conclusions
In summary, the challenging 1,2-cis glycosylation for
D-galactose with 1,2-cis-stereoselectivity at ambient tempera-
ture has been accomplished using our recently developed [Au]/
[Ag]-catalysed alkynyl carbonate donor chemistry. In this
endeavour, the effects of various factors on 1,2-cis galactopyra-
nosylation such as the solvent, temperature, catalyst, and pro-
tecting groups have been investigated. The optimized con-
ditions worked outstandingly with the monosaccharide as well
as at the branched di- and trisaccharide acceptor levels.
Furthermore, the synthesis of the hyper-branched tetrasacchar-
ide in the protected form was completed in 14 steps, which
proved that carbonate donor chemistry can be employed to
Scheme 5 Synthesis of hyper-branched tetrasaccharide 24.
synthesize complex and branched oligosaccharides.
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1319

View Article Online
Paper
Organic & Biomolecular Chemistry
obtain the desired hemi-acetal in 90–95% yield. This pro-
cedure was utilized for the synthesis of compounds explained
in sections 4.3.7 (4), 4.3.11 (5), 4.3.12 (6aβ), 4.3.13 (6aα), 4.3.14
4. Experimental section
4.1 General methods
Unless otherwise noted, materials were obtained from com- (6b), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e), 4.3.18 (6f) and 4.3.19
mercial suppliers and were used without further purification. (6g).
1-Ethynylcyclohexanol, p-nitrophenyl chloroformate and all
4.2.3. General procedure for the synthesis of ethynylcyclo-
metal salts were purchased from Sigma-Aldrich. Unless other- hexyl glycosyl carbonate donors. At first, DMAP (1 mmol) was
wise reported, all reactions were performed under a nitrogen added to a stirring solution of hemiacetal (1 mmol) in anhy-
atmosphere. The removal of the solvent in vacuo refers to distil- drous CH2Cl2 (10 mL) at 25 °C. After 20 min, reagent 12
lation using a rotary evaporator attached to an efficient (1.2 mmol) was added portion-wise (3×) after every 30 min and
vacuum pump. Products obtained as solids or syrups were stirred at 25 °C for 2–3 h. After the completion of the reaction
dried under high vacuum. Analytical thin-layer chromato- as indicated by TLC, the reaction mixture was concentrated in
graphy was performed on pre-coated silica plates (F254
,
vacuo and the oily residue was partially purified by silica gel
0.25 mm thickness); compounds were visualized with UV light column chromatography (n-hexane/EtOAc). Eluents containing
or by staining with anisaldehyde spray. IR spectra were alkynyl glycosyl carbonate along with trace quantities of
recorded on a FT-IR spectrometer. NMR spectra were recorded 4-nitrophenol were concentrated under diminished pressure.
either on a 400 system or a 500 MHz system with CDCl3 as the Furthermore, the crude residue was redissolved in CH2Cl2
solvent and TMS as the internal standard. High resolution (30 mL) and washed with sat. aq. NaHCO3 (3 × 10 mL) and
mass spectroscopy (HRMS) was performed using an ESI-TOF brine solution to remove 4-nitrophenol. The organic layer was
mass analyser. Low resolution mass spectroscopy (LRMS) was dried over Na2SO4 and concentrated in vacuo to obtain the
performed on a UPLC-MS system with SWADESI-TLC interface. alkynyl glycosyl carbonate donor in an excellent yield. This
procedure was utilized for the synthesis of compounds
4.2 Experimental procedures
explained in sections 4.3.7 (4), 4.3.11 (5), 4.3.12 (6aβ), 4.3.13
4.2.1. General procedure for the synthesis of allyl glyco- (6aα), 4.3.14 (6b), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e) and 4.3.18
sides. (a) To a rapidly stirring solution of sugar (1.0 mmol) in (6f).
anhydrous allyl alcohol, camphorsulfonic acid (0.5 mmol) was
4.2.4. General procedure for Bn/PMB/Nap protection of
added at 25 °C under a nitrogen atmosphere. The reaction alcohols. To an ice-cooled solution of alcohol (1 mmol) in
mixture was further heated to 80 °C and stirred for 6 h. After anhydrous DMF (10 mL), NaH (60% oil dispersion, 1.2 mmol
the completion of the reaction, the reaction mixture was per alcohol) was added and stirred for 10 minutes at 0 °C
cooled to 0 °C, the reaction was quenched with Et3N and the under a nitrogen atmosphere. BnBr/PMBCl/NapBr (1.2 mmol
reaction mixture was concentrated in vacuo to obtain a light per alcohol) was further added dropwise into the reaction
brown residue which was purified by column chromatography mixture followed by TBAI (0.1 mmol per alcohol) addition at
(CH2Cl2/MeOH) to obtain the desired allyl glycoside as a white 0 °C. The reaction mixture was gradually warmed up to 25 °C
solid. This procedure was utilized for the synthesis of com- and stirred for 4 h. After complete consumption of the alcohol
pounds explained in sections 4.3.1 (7) and 4.3.8 (13).
as indicated by TLC, the reaction mixture was poured into ice
(b) AcCl (0.3 mmol) was added dropwise to rapidly stirring cold water with vigorous shaking and extracted with ethyl
allyl alcohol (as a solvent) at 0 °C under a nitrogen atmo- acetate (3 × 20 mL) and the combined EtOAc layer was washed
sphere. After 30 min, sugar (1.0 mmol) was added and stirred with cold water and brine solution, dried over Na2SO4 and
at 25 °C for 1 h. The reaction mixture was further heated to evaporated in vacuo. The crude residue was further purified by
80 °C and refluxed for 6 h. After the completion of the reac- column chromatography (n-hexane/EtOAc) to obtain the Bn/
tion, the reaction mixture was cooled to 0 °C, the reaction was PMB/NAP ether as a pale-yellow coloured syrup. This procedure
quenched with Et3N and the reaction mixture was concen- was utilized for the synthesis of compounds explained in sec-
trated in vacuo to obtain a light brown residue which was puri- tions 4.3.2 (8), 4.3.9 (14), 4.3.12 (6aβ), 4.3.13 (6aα), 4.3.14 (6b),
fied by column chromatography (CH2Cl2/MeOH) to obtain the 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e) and 4.3.18 (6f).
desired allyl glycoside. This procedure was utilized for the syn-
4.2.5. General procedure for the deprotection of the iso-
thesis of compounds explained in sections 4.3.6 (11), 4.3.12 propylidene group. To a solution of the isopropylidene com-
(6aβ), 4.3.13 (6aα), 4.3.14 (6b), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 pound (1 mmol) in aqueous THF [THF : H2O = 7 : 3] (10 mL),
(6e) and 4.3.18 (6f).
4.2.2. General procedure for the deprotection of allyl glyco- was allowed to stir at 55 °C for 3 h. The progress of the reaction
sides. To solution of allyl glycoside (1 mmol) in and complete consumption of the starting material were
80% AcOH (2 mL) was added at 25 °C and the reaction mixture
a
a
3 : 1 mixture of CH3OH–CH2Cl2 (10 mL) was added dropwise checked by TLC. At the end of the reaction, the reaction was
PdCl2 (0.15 mmol) in CH3OH (1 mL) and stirred at 25 °C for quenched with sat. aq. NaHCO3 (20 mL) at 0 °C and the reac-
3 h. After the completion of the reaction, the reaction was tion mixture was extracted with ethyl acetate (50 mL). The
quenched by the addition of Et3N and the reaction mixture organic layer was washed with water (25 mL) and brine solu-
was concentrated in vacuo to obtain a residue that was purified tion (25 mL), dried over Na2SO4 and evaporated in vacuo to
by silica gel column chromatography (n-hexane/EtOAc) to obtain a crude residue which was purified by silica gel column
1320 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
chromatography (n-hexane/EtOAc) to afford the desired
4.2.10. General procedure for the deprotection of the
product. This procedure was utilized for the synthesis of com- TBDPS-ethers. To a solution of the silyl ether compound
pounds explained in sections 4.3.3 (9) and 4.3.10 (15). (1 mmol) in a 5 : 1 mixture of THF–Py (10 mL), HF·py (3 mmol)
4.2.6. General procedure for benzoate/acetate ester protec- was added dropwise at 0 °C under a nitrogen atmosphere and
tion of alcohols. To a solution of alcohol (1 mmol) in anhy- stirred at 25 °C. After 4 h, the reaction was quenched with 2 N
drous pyridine (10 mL), benzoyl chloride/acetic anhydride HCl at 0 °C and the reaction mixture was diluted with EtOAc
(1.2 mmol per alcohol) was added dropwise at 0 °C under a (30 mL) and washed with ice cold water (2 × 20 mL), sat. aq.
nitrogen atmosphere. The reaction mixture was gradually NaHCO3 (20 mL) and brine solution (20 mL) sequentially. The
warmed up to 25 °C and stirred for 6–12 h. The progress of the EtOAc layer was dried over anhydrous Na2SO4 and concen-
reaction and consumption of the starting alcohol were trated in vacuo. The crude residue was purified by silica gel
checked by TLC. After the completion of the reaction, the reac- column chromatography (n-hexane/EtOAc) to furnish the
tion was quenched by adding ice-cooled water, the reaction corresponding alcohol. This procedure was utilized for the syn-
mixture was extracted with CH2Cl2 (50 mL) and the CH2Cl2 thesis of compounds explained in section 4.3.5 (3).
layer was washed with 1 N HCl (2 × 50 mL), water, sat. aq.
4.2.11. General procedure for acetonide protection of diols.
NaHCO3 solution and finally brine solution. The combined To a rapidly stirring solution of diol (1.0 mmol) in anhydrous
organic layers were dried over anhydrous Na2SO4 and concen- acetone, 2,2-dimethoxy propane (1.5 mmol) and PTSA
trated in vacuo and the resulting crude residue was purified by (0.2 mmol) were added and the reaction mixture was stirred at
silica gel column chromatography (n-hexane/EtOAc) to obtain 25 °C overnight (12 h). After complete consumption of the
the desired compound. This procedure was utilized for the syn- diol, the reaction was quenched with Et3N and the reaction
thesis of compounds explained in sections 4.3.3 (9), 4.3.6 (11), mixture was concentrated in vacuo to obtain a light yellow
4.3.11 (5), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e), 4.3.18 (6f) and residue which was purified by column chromatography
4.3.19 (6g).
(n-hexane/EtOAc) to obtain the desired acetonide product as a
4.2.7. General procedure for TBDMS/TBDPS-protection of white solid. This procedure was utilized for the synthesis of
alcohols. To a rapidly stirring solution of alcohol (1.0 mmol) compounds explained in sections 4.3.1 (7) and 4.3.8 (13).
and imidazole (1.3 mmol) in anhydrous DMF (10 mL) was
4.2.12. General procedure for selective methyl ether protec-
added TBDMSCl/TBDPSCl (1.2 mmol) dropwise and stirred for tion. To a solution of alcohol (1 mmol) in toluene (10 mL),
4 h at 25 °C. At the end of the reaction, the reaction mixture Bu2SnO (1.2 mmol) was added and refluxed at 105 °C. After
was extracted with ethyl acetate (3 × 20 mL). The combined 2 h, MeI (3 mmol) and TBAI (0.2 mmol) were added and the
organic layer was washed with water (2 × 50 mL) and brine reaction mixture was stirred at 25 °C for another 3 h. The reac-
solution (1 × 50 mL), dried over Na2SO4 and evaporated in tion was monitored by TLC and upon completion of the reac-
vacuo to obtain a crude residue which was purified by silica gel tion, the reaction mixture was concentrated under reduced
column chromatography (n-hexane/EtOAc) to afford the pressure to obtain the crude residue which was purified by
desired product. This procedure was utilized for the synthesis silica gel column chromatography (CH2Cl2/MeOH) to afford
of compounds explained in sections 4.3.4 (10) and 4.3.19 (6g).
the desired methyl ether as a colourless syrup. This procedure
4.2.8. General procedure for the saponification of ester. To was utilized for the synthesis of compounds explained in
a solution of benzoate/acetate (1 mmol) in a 3 : 1 mixture of section 4.3.10 (15).
anhydrous CH2Cl2–MeOH (20 mL), freshly prepared 1 M
4.2.13. General procedure for benzylidine protection of
NaOMe in MeOH (0.3 mmol) was added and the reaction diols. To a rapidly stirring solution of diol (1.0 mmol) in anhy-
mixture was stirred at 25 °C for 2 h. After complete conversion, drous DMF, benzaldehyde 1,1-dimethylacetal (1.5 mmol) and
the reaction mixture was neutralized with Amberlite IR120 PTSA (0.2 mmol) were added and the reaction mixture was
resin and concentrated in vacuo to obtain a residue that was stirred at 25 °C overnight (12 h). After complete consumption
purified by column chromatography (n-hexane/EtOAc) to of the diol, the reaction was quenched with Et3N and the reac-
afford the desired alcohol. This procedure was utilized for the tion mixture was extracted with ethyl acetate (3 × 20 mL). The
synthesis of compounds explained in section 4.3.4 (10).
combined organic layer was washed with water (2 × 50 mL)
4.2.9. General procedure for levulinoate ester protection of and brine solution (1 × 50 mL), dried over Na2SO4 and evapor-
alcohols. To a stirring solution of alcohol (1.0 mmol) in anhy- ated in vacuo to obtain a crude residue which was purified by
drous CH2Cl2 (4 mL), DMAP (1.0 mmol), levulinic acid silica gel column chromatography (n-hexane/EtOAc) to afford
(1.5 mmol) and N,N‘-diisopropylcarbodiimide (1.5 mmol) were the desired product. This procedure was utilized for the syn-
added sequentially at 0 °C under a nitrogen atmosphere. The thesis of compounds explained in sections 4.3.12 (6aβ), 4.3.13
reaction mixture was gradually warmed up to 25 °C and stirred (6aα), 4.3.14 (6b), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e) and 4.3.18
for 4 h. After complete consumption of the starting alcohol, (6f).
the reaction mixture was concentrated in vacuo and purified by
4.2.14. General procedure for the deprotection of the ben-
silica gel column chromatography (n-hexane/EtOAc) to afford zylidine group. To a solution of the benzylidine compound
the corresponding levulinoate ester. This procedure was uti- (1 mmol) in MeOH was added PTSA (0.2 mmol) and the reac-
lized for the synthesis of compounds explained in section tion mixture was stirred at 25 °C for 30 minutes. After the com-
4.3.4 (10).
pletion of the reaction (as indicated by TLC), the reaction was
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1321

View Article Online
Paper
Organic & Biomolecular Chemistry
quenched with Et3N and the reaction mixture was concen- 133.8; HRMS (ESI): m/z calcd for C12H20O5, [M + Na]+:
trated in vacuo to obtain a pale yellow residue which was puri- 267.1208; found: 267.1204.
fied by column chromatography (n-hexane/EtOAc) to afford the
4.3.2. Allyl
2-O-(p-methoxybenzyl)-3,4-O-isopropylidene
desired product. This procedure was utilized for the synthesis α-L-fucopyranoside (8). The title compound was prepared
of compounds explained in sections 4.3.12 (6aβ), 4.3.13 (6aα), according to the general procedure 4.2.4; syrup (4.628 g, 94%
4.3.14 (6b), 4.3.15 (6c), 4.3.16 (6d), 4.3.17 (6e), 4.3.18 (6f) and yield); [α]D25 (CHCl3, c 1.0): −97.2; IR (cm−1, CHCl3):1605, 1440,
4.3.19 (6g).
1335, 1245, 1078, 1026, 940, 710; 1H NMR (400.31 MHz,
4.2.15. Procedure for glycosylation. To a stirred solution of CDCl3): δ 1.23 (d, J = 6.7 Hz, 3H), 1.34 (s, 3H), 1.27 (s, 3H), 3.42
the alkynyl carbonate donor (1 mmol) and acceptor (1 mmol) (dd, J = 7.9, 3.6 Hz, 1H), 3.72 (s, 3H), 3.91 (dd, J = 13.0, 6.2 Hz,
in an anhydrous solvent (4 mL) containing 4 Å MS powder 1H), 3.96 (dd, J = 5.5, 2.5 Hz, 1H), 4.01–4.10 (m, 2H), 4.24 (dd,
(100 mg), the Au-complex (0.10 mmol) and the Ag-salt J = 7.8, 5.5 Hz, 1H), 4.56 (d, J = 12.2 Hz, 1H), 4.65 (d, J = 12.2
(0.10 mmol) were added and stirred at 25 °C. Upon completion Hz, 1H), 4.68 (d, J = 3.6 Hz, 1H), 5.13 (dd, J = 10.4, 1.3 Hz, 1H),
of the reaction (in 15 min), the reaction was quenched by the 5.24 (dd, J = 17.2, 1.5 Hz, 1H), 5.86 (dddd, J = 17.1, 10.4, 6.1,
addition of Et3N and the reaction mixture was concentrated in 5.3 Hz, 1H), 6.79 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.6 Hz, 2H);
vacuo to obtain a residue that was purified by silica gel column 13C NMR (100.67 MHz, CDCl3): δ 16.4, 26.5, 28.3, 55.4, 63.3,
chromatography (n-hexane/EtOAc) to afford the desired glyco- 68.4, 72.0, 76.0, 76.0, 76.3, 96.2, 108.8, 113.8, 113.8, 117.8,
side. This procedure was utilized for the synthesis of com- 129.6, 129.6, 130.6, 134.0, 159.4; HRMS (ESI): m/z calcd for
pounds explained in sections 4.3.20 (19), 4.3.21 (20), 4.3.23 C19H26O7, [M + Na]+: 387.1784; found: 387.1780.
(22), 4.3.26 (25) and 4.3.28 (26).
4.3.3. Allyl 2-O-(p-methoxybenzyl)-3-O-acetyl α-L-fucopyra-
4.2.16. General procedure for the deprotection of PMB noside (9). The title compound was prepared according to the
ethers. To a solution of the PMB ether compound (1 mmol) in general procedures 4.2.5 and 4.2.6; syrup (3.604 g, 78% yield);
the 20 : 1 mixture of CH2Cl2–H2O (10 mL) was added DDQ [α]D25 (CHCl3, c 1.0): −132.7; IR (cm−1, CHCl3):1730, 1610, 1430,
1
(2 mmol) at 25 °C and stirred for 2 h. After the completion of 1328, 1239, 1063, 1020, 706; H NMR (400.31 MHz, CDCl3): δ
the reaction (as indicated by TLC), the reaction was quenched 1.14 (d, J = 6.6 Hz, 3H), 2.02 (s, 3H), 3.72 (s, 3H), 3.78 (dd, J =
with Et3N and the reaction mixture was concentrated in vacuo 10.5, 3.7 Hz, 1H), 3.82 (s, 1H), 3.93 (ddd, J = 13.0, 7.1, 3.8 Hz,
to obtain a dark yellow residue which was purified by silica gel 1H), 3.98 (q, J = 6.6 Hz, 1H), 4.07 (ddd, J = 7.2, 5.2, 3.3 Hz, 1H),
column chromatography (n-hexane/EtOAc) to obtain the 4.48 (dd, J = 29.4, 12.0 Hz, 2H), 4.71 (d, J = 3.7 Hz, 1H),
desired alcohol as a colourless syrup. This procedure was uti- 5.07–5.20 (m, 2H), 5.24 (dd, J = 17.2, 1.6 Hz, 1H), 5.89 (dddd, J
lized for the synthesis of compounds explained in sections = 17.1, 10.4, 6.1, 5.3 Hz, 1H), 6.78 (d, J = 8.7 Hz, 2H), 7.17 (d, J
4.3.22 (21) and 4.3.27 (26).
= 8.7 Hz, 2H); 13C NMR (100.67 MHz, CDCl3): δ 16.0, 21.2,
4.2.17. General procedure for the deprotection of levulino- 55.3, 65.4, 68.5, 70.8, 72.5, 72.8, 72.9, 96.2, 113.8, 113.8, 117.8,
ates. To a rapidly stirring solution of the levulinoate com- 129.5, 129.5, 130.4, 133.9, 1559.4, 170.3; HRMS (ESI-MS): m/z
pound (1.0 mmol) in MeOH (10 mL), hydrazine acetate calcd for C19H26O7, [M + Na]+: 389.1576; found: 389.1579.
(4 mmol) in THF (4 mL) was added at 25 °C. After 4 h, the reac-
4.3.4. Allyl 2-O-(p-methoxybenzyl)-3-O-(4-oxopentanoyl)-4-
tion was quenched with ice cold 1 N HCl solution and the reac- O-(tert-butyldimethyl silyl) α-L-fucopyranoside (10). The title
tion mixture was extracted with EtOAc and washed with water, compound was prepared according to the general procedures
sat. aq. NaHCO3 and brine solution sequentially. The organic 4.2.7, 4.2.8 and 4.2.9; syrup (4.525 g, 87% yield); [α]D25 (CHCl3, c
layer was dried over Na2SO4 and concentrated in vacuo to 1.0): −84.8; IR (cm−1, CHCl3): 1726, 1613, 1448, 1355, 1269,
1
obtain the crude residue which was purified by silica gel 1107, 1025, 715; H NMR (400.31 MHz, CDCl3): δ 0.07 (s, 3H),
column chromatography (n-hexane/EtOAc) to afford the 0.09 (s, 3H), 0.87 (s, 9H), 1.08 (d, J = 6.6 Hz, 3H), 2.17 (s, 3H),
desired alcohol in a good yield. This procedure was utilized for 2.63–2.78 (m, 4H), 3.58 (dd, J = 9.7, 3.7 Hz, 1H), 3.79–3.80 (m,
the synthesis of compounds explained in sections 4.3.24 (23) 3H), 3.94–4.05 (m, 2H), 4.08–4.14 (m, 2H), 4.48 (d, J = 11.8 Hz,
and 4.3.25 (24).
1H), 4.61–4.76 (m, 2H), 5.10 (d, J = 3.4 Hz, 1H), 5.19 (d, J = 10.4
Hz, 1H), 5.30 (d, J = 17.2 Hz, 1H), 5.91 (ddt, J = 16.7, 11.3, 5.8
Hz, 1H), 6.86 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H); 13C
NMR (100.67 MHz, CDCl3): δ −4.9, −4.6, 16.1, 18.0, 25.8, 25.8,
4.3. Characterization data
4.3.1. Allyl 3,4-O-isopropylidene α-L-fucopyranoside (7). 25.8, 28.1, 29.9, 38.1, 55.3, 64.7, 68.4, 69.2, 72.9, 74.6, 76.1,
The title compound was prepared according to the general pro- 96.5, 113.7, 113.7, 117.8, 129.6, 129.6, 130.8, 134.1, 159.3,
cedures 4.2.1a and 4.2.11; syrup (3.352 g, 75% yield); [α]D25 172.3, 206.3; HRMS (ESI): m/z calcd for C28H44O8Si, [M + Na]+:
(CHCl3, c 1.0): −126.4; 1H NMR (400.31 MHz, CDCl3): δ 1.24 (d, 559.2703; found: 559.2697.
J = 6.7 Hz, 3H), 1.28 (s, 3H), 1.43 (s, 3H), 2.68 (s, 1H), 3.57–3.79
4.3.5. Allyl
2-O-(p-methoxybenzyl)-3-O-(4-oxopentanoyl)
(m, 1H), 3.94–4.01 (m, 2H), 4.06 (qd, J = 6.6, 2.3 Hz, 1H), α-L-fucopyranoside (3). The title compound was prepared
4.12–4.19 (m, 1H), 4.78 (d, J = 3.9 Hz, 1H), 5.13 (ddd, J = 10.4, according to the general procedure 4.2.10; syrup (3.410 g, 96%
2.8, 1.3 Hz, 1H), 5.23 (dq, J = 17.2, 1.6 Hz, 1H), 5.85 (dddd, J = yield); [α]D25 (CHCl3, c 1.0): −38.5; IR (cm−1, CHCl3): 1720, 1610,
17.1, 10.4, 6.1, 5.3 Hz, 1H); 13C NMR (100.67 MHz, CDCl3): δ 1453, 1365, 1263, 1090, 1034, 715; 1H NMR (400.31 MHz,
16.2, 25.9, 27.8, 63.9, 68.4, 69.4, 75.7, 76.2, 96.8, 109.1, 117.6, CDCl3): δ 1.07 (d, J = 6.6 Hz, 3H), 2.13 (s, 3H), 2.55–2.80 (m,
1322 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
5H), 3.60 (dd, J = 10.1, 3.6 Hz, 1H), 3.91 (dd, J = 12.9, 6.4 Hz,
4.3.9. Allyl 2,3-O-isopropylidene-4-O-benzyl α-L-rhamnopyr-
1H), 3.75 (s, 3H), 4.00 (q, J = 6.5 Hz, 1H), 4.05–4.13 (m, 1H), anoside (14). The title compound was prepared according to
4.53–4.62 (m, 2H), 4.79 (d, J = 3.5 Hz, 1H), 5.08–5.21 (m, 2H), the general procedure 4.2.4; syrup (4.034 g, 92% yield); [α]2D5
5.28 (dd, J = 17.2, 1.4 Hz, 1H), 5.87 (dddd, J = 17.1, 10.4, 6.1, (CHCl3, c 1.0): −59.4; IR (cm−1, CHCl3): 1610, 1429, 1320,
5.3 Hz, 1H), 6.83 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.5 Hz, 1H); 1235, 1067, 1045, 718; 1H NMR (400.31 MHz, CDCl3): δ 1.28 (d,
13C NMR (100.67 MHz, CDCl3): δ 16.1, 28.1, 29.9, 38.2, 55.3, J = 6.3 Hz, 3H), 1.37 (s, 3H), 1.50 (s, 3H), 3.22 (dd, J = 9.8, 7.1
64.9, 68.1, 68.6, 72.4, 73.6, 76.3, 96.0, 113.9, 113.9, 117.9, 129.8 Hz, 1H), 3.71 (dd, J = 9.8, 6.2 Hz, 1H), 3.93–4.03 (m, 1H),
(3C), 130.3, 133.9, 172.9, 206.9; HRMS (ESI): m/z calcd for 4.12–4.19 (m, 2H), 4.24–4.31 (m, 1H), 4.62 (d, J = 11.6 Hz, 1H),
C22H30O8, [M + Na]+: 445.1838; found: 445.1834.
4.90 (d, J = 11.6 Hz, 1H), 5.00 (s, 1H), 5.20 (ddd, J = 10.4, 2.7,
4.3.6. Allyl 2,3,4-tri-O-benzoyl α/β-D-xylopyranoside [α : β 1.2 Hz, 1H), 5.23–5.34 (m, 1H), 5.89 (dddd, J = 16.7, 10.4, 6.2,
(2.0 : 1.0)] (11). The title compound was prepared according to 5.3 Hz, 1H), 7.24–7.29 (m, 1H), 7.30–7.37 (m, 4H); 13C NMR
the general procedures 4.2.1b and 4.2.6; white solid (5.097 g, (100.67 MHz, CDCl3): δ 17.9, 26.5, 28.1, 64.7, 68.0, 73.1, 76.2,
76% yield); mp 74.5 °C; [α]D25 (CHCl3, c 1.0): +56.3; IR (cm−1
CHCl3): 3277, 2939, 1720, 1634, 1425, 1250, 1095, 910, 717; H 133.8, 138.5; HRMS (ESI-MS): m/z calcd for C19H26O5, [M +
NMR (400.31 MHz, CDCl3): δ 3.75–4.18 (m, 6H), 4.29–4.38 (m, Na]+: 357.1678; found: 357.1674.
,
78.8, 81.3, 96.2, 109.3, 117.8, 127.7, 128.1, 128.1, 128.4, 128.4,
1
2H), 4.45–5.24 (m, 4H), 5.32–5.37 (m, 5H), 5.42–5.97 (m, 4H),
4.3.10. Allyl 3-O-methyl-4-O-benzyl α-L-rhamnopyranoside
6.24 (t, J = 9.4 Hz, 1H), 7.28–7.59 (m, 18H), 7.96–8.06 (m, 12H); (15). The title compound was prepared according to the
13C NMR (100.67 MHz, CDCl3): δ 58.8, 61.1, 68.8, 69.1, 69.4, general procedures 4.2.5 and 4.2.12; syrup (2.451 g, 68% yield);
70.0, 70.2, 70.2, 70.3, 71.9, 95.3, 98.9, 117.7, 117.8, 128.3–128.4 [α]D25 (CHCl3, c 1.0): −51.6; IR (cm−1, CHCl3): 1622, 1420, 1320,
(12C), 129.1, 129.1, 129.2, 129.3, 129.4, 129.4, 129.7–129.9 1228, 1055, 1036, 720; 1H NMR (400.31 MHz, CDCl3): 1.30 (d, J
(12C), 133.1, 133.3, 133.3, 133.4, 133.4, 133.4, 133.5, 133.5, = 6.3 Hz, 3H), 2.81 (s, 1H), 3.39 (t, J = 9.3 Hz, 1H), 3.48 (s, 3H),
165.2, 165.4, 165.6, 165.6, 165.8, 165.8; HRMS (ESI-MS): m/z 3.57 (dd, J = 9.1, 3.3 Hz, 1H), 3.72 (dq, J = 9.7, 6.3 Hz, 1H), 3.96
calcd for C29H26O8, [M + Na]+: 525.1525; found: 525.1519.
4.3.7. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3,4-tri-O-
(ddt, J = 12.9, 6.2, 1.3 Hz, 1H), 4.06 (s, 1H), 4.10–4.18 (m, 1H),
4.61 (d, J = 11.0 Hz, 1H), 4.84 (d, J = 4.1 Hz, 1H), 4.85 (d, J = 5.4
benzoyl α/β-D-xylopyranoside [α : β (1.0 : 1.5)] (4). The title com- Hz, 1H), 5.17 (ddd, J = 10.4, 2.8, 1.2 Hz, 1H), 5.27 (ddd, J =
pound was prepared according to the general procedures 4.2.2 17.2, 3.2, 1.6 Hz, 1H), 5.88 (dddd, J = 21.9, 10.4, 6.1, 5.2 Hz,
and 4.2.3; white solid (5.175 g, 85% yield); mp 52.8 °C; [α]D25 1H), 7.24–7.29 (m, 1H), 7.30–7.37 (m, 4H); 13C NMR
(CHCl3, c 1.0): +37.5; IR (cm−1, CHCl3): 3277, 2939, 2862, 1727, (100.67 MHz, CDCl3): δ 17.9, 57.4, 67.3, 67.8, 67.9, 75.2, 79.9,
1600, 1451, 1263, 1096, 908, 709; 1H NMR (400.31 MHz, 81.8, 98.3, 117.4, 127.6, 127.9, 127.9, 128.3, 128.3, 133.8, 138.5;
CDCl3): δ 1.29–1.40 (m, 2H), 1.47–1.76 (m, 10H), 1.77–2.28 (m, HRMS (ESI): m/z calcd for C17H24O5, [M + Na]+: 331.1521;
8H), 2.48 (s, 1H), 2.65 (s, 1H), 3.95–4.16 (m, 2H), 4.27–4.59 (m, found: 331.1522.
2H), 5.21–5.60 (m, 4H), 5.71–6.53 (m, 4H), 7.29–7.61 (m, 18H),
4.3.11. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2-O-benzoyl-
7.89–8.16 (m, 12H); 13C NMR (100.67 MHz, CDCl3): δ 22.4, 3-O-methyl-4-O-benzyl α-L-rhamnopyranoside (5). The title com-
22.5, 22.5, 22.5, 24.9, 24.9, 36.6, 36.7, 36.7, 36.7, 61.2, 61.4, pound was prepared according to the general procedures 4.2.6,
67.6, 67.9, 68.0, 69.5, 69.7, 70.3, 75.3, 75.4, 78.5, 78.7, 82.4, 4.2.2 and 4.2.3; white solid (3.340 g, 82% yield); mp 66.3 °C;
82.4, 92.8, 94.8, 128.4–128.5 (12C), 128.8, 128.9 (2C), 129.0, [α]D25 (CHCl3, c 1.0): −40.6; IR (cm−1, CHCl3): 3293, 2940, 1740,
129.1, 129.2, 129.7–130.1 (12C), 133.3, 133.4, 133.5, 133.5, 1465, 1372, 1265, 1090, 1032, 708; 1H NMR (400.31 MHz,
133.5, 133.5, 150.8, 150.9, 164.9, 164.9, 165.4, 165.5, 165.5, CDCl3): δ 1.24–1.30 (m, 1H), 1.44 (d, J = 6.0 Hz, 3H), 1.49–1.67
165.8; HRMS (ESI): m/z calcd for C35H32O10, [M + Na]+: (m, 5H), 1.76–1.88 (m, 2H), 2.11–2.17 (m, 2H), 2.63 (s, 1H),
635.1893; found: 635.1891.
3.43–3.50 (m, 4H), 3.51–3.62 (m, 2H), 4.63 (d, J = 10.9 Hz, 1H),
4.3.8. Allyl 2,3-O-isopropylidene α/β-L-rhamnopyranoside 4.89 (d, J = 10.9 Hz, 1H), 5.71 (s, 1H), 5.86 (d, J = 2.9 Hz, 1H),
[α : β = 8 : 1] (13). The title compound was prepared according 7.21–7.39 (m, 5H), 7.45–7.49 (m, 2H), 7.57–7.60 (m, 1H),
to the general procedures 4.2.1a and 4.2.11; syrup (3.258 g, 8.10–8.12 (m, 2H); 13C NMR (100.67 MHz, CDCl3): δ 18.2, 18.2,
73% yield). For characterization, an analytical sample was sub- 22.5, 25.0, 36.6, 36.8, 57.6, 67.6, 72.7, 75.4, 75.5, 78.7, 79.4,
jected to flash purification and the major compound was 82.6, 82.8, 94.0, 127.9, 128.2 (2C), 128.5 (4C), 129.9, 130.2 (2C),
characterized to be the α-anomer. [α]D25 (CHCl3, c 1.0): −34.9; 133.3, 138.3, 151.1, 165.8; HRMS (ESI): m/z calcd for
1H NMR (400.31 MHz, CDCl3): δ 1.29 (d, J = 6.3 Hz, 3H), 1.34 [C30H34O8Na]+: 545.2151; found: 545.2156.
(s, 3H), 1.52 (s, 3H), 2.71 (bs, 1H), 3.39 (dd, J = 8.5, 8.0 Hz, 1H),
4.3.12. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3,4,6-tetra-
3.68 (dq, J = 9.3, 6.1 Hz, 1H), 4.01 (ddt, J = 12.8, 6.2, 1.3 Hz, O-benzyl β-D-galactopyranoside (6aβ). The title compound was
1H), 4.09 (dd, J = 8.5, 8.0 Hz, 1H), 4.15 (d, J = 4.0 Hz, 1H), 4.19 prepared according to the general procedures 4.2.1b, 4.2.13,
(ddt, J = 12.8, 6.2, 1.3 Hz), 5.00 (s, 1H), 5.20 (ddd, J = 10.4, 2.7, 4.2.4, 4.2.14, 4.2.2 and 4.2.3; syrup (2.250 g, 45% yield); [α]2D5
1.2 Hz, 1H), 5.29 (ddd, J = 17.6, 3.1, 1.6 Hz, 1H), 5.89 (dddd, J = (CHCl3, c 1.0): +25.7; IR (cm−1, CHCl3): 3280, 3025, 2922, 1760,
1
16.7, 10.4, 6.2, 5.3 Hz, 1H); 13C NMR (100.67 MHz, CDCl3): δ 1492, 1460, 1255, 1230, 1089, 914, 726; H NMR (400.31 MHz,
17.6, 26.3, 28.1, 66.1, 68.1, 74.6, 76.0, 78.5, 96.4, 109.6, 118.0, CDCl3): δ 1.33–1.41 (m, 1H), 1.52–1.58 (m, 1H), 1.62–1.72 (m,
133.7; HRMS (ESI): m/z calcd for C12H20O5, [M + Na]+: 4H), 1.90–1.97 (m, 2H), 2.15–2.22 (m, 2H), 2.62 (s, 1H),
267.1208; found: 267.1213.
3.59–3.76 (m, 4H), 3.95–4.06 (m, 2H), 4.47 (q, J = 11.7 Hz, 2H),
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1323

View Article Online
Paper
Organic & Biomolecular Chemistry
4.65 (d, J = 11.5 Hz, 1H), 4.76 (s, 2H), 4.85 (s, 2H), 5.00 (d, J = 6H), 5.51–6.25 (m, 4H), 7.25–7.36 (m, 20H); 13C NMR
11.5 Hz, 1H), 5.53 (d, J = 8.0 Hz, 1H), 7.09–7.54 (m, 20H); 13C (100.67 MHz, CDCl3): δ 20.8 (2C), 20.9 (2C), 22.5 (2C), 22.9,
NMR (100.67 MHz, CDCl3): δ 22.6 (2C), 25.0, 36.8, 36.9, 68.1, 22.6, 25.0 (2C), 36.6, 36.8, 36.9 (2C), 61.7, 62.1, 66.2, 67.2, 69.3,
73.0, 73.3, 73.6, 74.3, 74.8, 75.1, 75.6, 78.2, 78.4, 82.3, 82.8, 71.8, 72.2, 72.3, 73.7, 74.6, 75.2, 75.4, 75.6 (2C), 77.5, 78.2,
97.9, 127.7 (3C), 127.8 (2C), 128.1 (4C), 128.2 (2C), 128.4 (3C), 78.5, 79.3, 82.6, 82.9, 94.2, 97.3, 127.8–128.1 (10C),
128.6 (4C), 137.9, 138.4, 138.4, 138.7, 151.5; HRMS (ESI-MS): 128.2–128.4 (8C), 128.5 (2C), 137.6, 138.0 (3C), 151.2, 151.4,
m/z calcd for C43H46O8, [M + Na]+: 713.3090; found: 713.3087.
4.3.13. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3,4,6-tetra- [M + Na]+: 617.2363; found: 617.2358.
170.3 (2C), 170.5 (2C); HRMS (ESI): m/z calcd for C33H38O10
,
O-benzyl α-D-galactopyranoside (6aα). The title compound was
prepared according to the general procedures 4.2.1b, 4.2.13, benzyl-4,6-di-O-benzoyl
4.3.16. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3-di-O-
α/β-D-galactopyranoside
[α : β
4.2.4, 4.2.14, 4.2.2 and 4.2.3; syrup (760 mg, 15% yield); [α]D25 (1.0 : 2.0)] (6d). The title compound was prepared according to
(CHCl3, c 1.0): +30.2; IR (cm−1, CHCl3): 3275, 3020, 2935, 1765, the general procedures 4.2.1b, 4.2.13, 4.2.4, 4.2.14, 4.2.6,
1
1486, 1468, 1250, 1237, 1076, 910, 715; H NMR (400.31 MHz, 4.2.10 and 4.2.11; white solid (1.513 g, 58% yield); mp 62.6 °C;
CDCl3): δ 1.29–1.36 (m, 1H), 1.52–1.59 (m, 1H), 1.60–1.68 (m, [α]D25 (CHCl3, c 1.0): +64.2; IR (cm−1, CHCl3): 3262, 2930, 1736,
4H), 1.84–1.92 (m, 2H), 2.16–2.23 (m, 2H), 2.58 (s, 1H), 3.58 1447, 1362, 1256, 1105, 978, 716; 1H NMR (400.31 MHz,
(dd, J = 6.5, 1.2 Hz, 2H), 3.96 (dd, J = 10.1, 2.7 Hz, 1H), 4.05 (d, CDCl3): δ 1.28–1.38 (m, 2H), 1.52–1.70 (m, 10H), 1.83–1.96 (m,
J = 1.8 Hz, 1H), 4.13 (t, J = 6.5 Hz, 1H), 4.19 (dd, J = 10.0, 3.7 4H), 2.16–2.27 (m, 4H), 2.59 (s, 1H), 2.65 (s, 1H), 3.78–4.42 (m,
Hz, 1H), 4.42 (d, J = 11.8 Hz, 1H), 4.50 (d, J = 11.8 Hz, 1H), 4.59 7H), 4.43–4.65 (m, 5H), 4.67–4.77 (m, 4H), 4.77–4.90 (m, 2H),
(d, J = 11.3 Hz, 1H), 4.72–4.80 (m, 3H), 4.86 (d, J = 11.8 Hz, 5.67–6.36 (m, 4H), 7.25–7.36 (m, 20H), 7.41–7.50 (m, 8H),
1H), 4.97 (d, J = 11.3 Hz, 1H), 6.28 (d, J = 3.7 Hz, 1H), 7.26–7.42 7.52–7.64 (m, 4H), 8.00–8.18 (m, 8H); 13C NMR (100.67 MHz,
(m, 20H); 13C NMR (100.67 MHz, CDCl3): δ 22.6 (2C), 25.1, CDCl3): δ 22.6, 22.7 (3C), 25.1 (2C), 36.8 (2C), 37.0 (2C), 62.5,
36.7, 37.0, 68.5, 72.1, 73.2, 73.5, 73.6, 74.7, 75.1, 75.6, 78.0, 62.9, 67.1, 68.2, 69.7, 72.1, 72.2, 72.3, 73.8, 74.3, 75.3, 75.5,
78.6, 82.3, 82.8, 94.6, 127.5 (2C), 127.7 (2C), 127.8, 127.9, 128.0 75.7, 75.9, 77.7, 78.3, 78.8, 79.6, 82.6, 82.8, 94.4, 97.5, 127.7
(2C), 128.1 (2C), 128.3 (2C), 128.4 (4C), 128.5 (4C), 138.0, 138.2, (2C), 127.9 (4C), 127.6, 128.2 (6C), 128.4 (4C), 128.5 (8C), 128.6
138.6, 138.8, 151.7; HRMS (ESI): m/z calcd for C43H46O8, [M + (2C), 128.7, 129.6 (2C), 129.7 (2C), 130.0 (4C), 130.1, 130.1,
Na]+: 713.3090; found: 713.3092.
130.2, 130.2, 133.3, 133.3, 133.5, 133.5, 137.6, 137.9, 138.0,
4.3.14. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3-di-O- 138.2, 151.2, 151.4, 165.7, 165.8, 166.2, 166.2; HRMS (ESI): m/z
benzyl-4,6-di-O-(naphthalen-1-yl methyl) α/β-D-galactopyra- calcd for C43H42O10, [M + Na]+: 741.2676; found: 741.2676.
noside [α : β (1.0 : 8.0)] (6b). The title compound was prepared
4.3.17. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-4-O-acetyl-
according to the general procedures 4.2.1b, 4.2.13, 4.2.4, 2,3,6-tri-O-benzyl α/β-D-galactopyranoside [α : β (1.0 : 3.0)] (6e).
4.2.14, 4.2.2 and 4.2.3; white solid (1.489 g, 52% yield); mp The title compound was prepared according to the general pro-
78.5 °C; [α]D25 (CHCl3, c 1.0): +60.5; IR (cm−1, CHCl3): 3245, cedures 4.2.1b, 4.2.13, 4.2.4, 4.2.14, 4.2.6, 4.2.2 and 4.2.3;
2910, 1710, 1628, 1435, 1277, 1102, 924, 718; 1H NMR syrup (1.056 g, 45% yield); [α]D25 (CHCl3, c 1.0): +54.1; IR (cm−1
,
(400.31 MHz, CDCl3): δ 1.35–1.39 (m, 2H), 1.53–1.79 (m, 10H), CHCl3): 3028, 2926, 1740, 1509, 1450, 1362, 1225, 1095, 908,
1
1.90–2.01 (m, 4H), 2.18–2.28 (m, 4H), 2.63–2.68 (m, 2H), 735, 698; H NMR (400.31 MHz, CDCl3): δ 1.22–1.43 (m, 2H),
3.70–4.32 (m, 12H), 4.55–4.69 (m, 4H), 4.80–5.19 (m, 12H), 1.48–1.74 (m, 10H), 1.84–2.00 (m, 4H), 2.07 (s, 3H), 2.09 (s,
5.60–6.42 (m, 2H), 7.30–7.58 (m, 32H), 7.71–7.84 (m, 16H); 13C 3H), 2.15–2.25 (m, 4H), 2.61 (s, 1H), 2.64 (s, 1H), 3.45–3.63 (m,
NMR (100.67 MHz, CDCl3): δ 22.6 (4C), 25.1, (2C), 36.8 (2C), 4H), 3.65–3.81 (m, 3H), 3.84–4.33 (m, 3H), 4.45–4.48 (m, 2H),
36.9 (2C), 68.2, 68.6, 72.3, 73.1, 73.3, 73.3, 73.6, 73.8, 74.4, 4.51–4.66 (m, 4H), 4.66–4.94 (m, 6H), 5.55–6.30 (m, 4H),
74.6, 74.8, 75.1, 75.3, 75.3, 75.6, 75.8, 78.1, 78.3, 78.5, 78.8, 6.97–7.65 (m, 30H); 13C NMR (100.67 MHz, CDCl3): δ 21.0 (2C),
82.4, 82.4, 82.9, 83.1, 94.7, 98.0, 126.0–126.4 (12C), 22.6 (4C), 25.1 (2C), 36.8 (4C), 66.4–68.1 (4C), 70.5, 72.1, 72.2,
126.8–127.0 (6C), 127.6–127.9 (14C), 128.1–128.3 (10C), 73.0, 73.7 (3C), 74.7, 75.3, 75.4, 75.6, 75.9, 77.7, 78.2, 78.4,
128.4–128.6 (10C), 133.1, 133.2, 133.3, 133.3, 135.4, 135.4, 79.6, 82.7, 82.9, 94.3, 97.5, 127.8–128.1 (10C), 128.2–128.4
136.0, 136.2, 138.3, 138.4, 138.5, 138.9, 151.6, 151.8; HRMS (11C), 128.5–128.6 (9C), 137.7 (2C), 137.8, 138.2, 138.2, 138.3,
(ESI): m/z calcd for C51H50O8, [M + Na]+: 813.3403; found: 151.3, 151.5, 170.3, 170.3; HRMS (ESI): m/z calcd for C38H42O9,
813.3400.
[M + Na]+: 665.2727; found: 665.2734.
4.3.15. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3-di-O-
4.3.18. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3-di-O-
benzyl-4,6-di-O-acetyl
α/β-D-galactopyranoside
[α : β benzyl-4-O-acetyl-6-O-(naphthalen-1-yl methyl) α/β-D-galac-
(1.0 : 2.5)] (6c). The title compound was prepared according to topyranoside [α : β (1.0 : 3.5)] (6f). The title compound was
the general procedures 4.2.1b, 4.2.13, 4.2.4, 4.2.14, 4.2.5, 4.2.2 prepared according to the general procedures 4.2.1b, 4.2.13,
and 4.2.3; syrup (1.216 g, 56% yield); [α]D25 (CHCl3, c 1.0): +49.3; 4.2.4, 4.2.14, 4.2.6, 4.2.2 and 4.2.3; white solid (1.164 g, 46%
IR (cm−1, CHCl3): 3271, 2937, 1730, 1453, 1368, 1267, 1090, yield); mp 72.5 °C; [α]D25 (CHCl3, c 1.0): +82.3; IR (cm−1, CHCl3):
1
1025, 723; H NMR (400.31 MHz, CDCl3): δ 1.26–1.40 (m, 2H), 2925, 2858, 2320, 1735, 1604, 1513, 1455, 1360, 1265, 1110,
1
1.46–1.72 (m, 10H), 1.85–1.89 (m, 4H), 2.04 (s, 3H), 2.05 (s, 968, 711; H NMR (400.31 MHz, CDCl3): δ 1.25–1.41 (m, 2H),
3H), 2.09–2.22 (m, 10H), 2.62 (s, 1H), 2.64 (s, 1H), 3.65–3.95 1.47–1.77 (m, 10H), 1.91–1.93 (m, 4H), 2.03 (s, 3H), 2.04 (s,
(m, 5H), 4.11–4.29 (m, 5H), 4.50–4.58 (m, 2H), 4.71–4.81 (m, 3H), 2.14–2.18 (m, 4H), 2.50–2.66 (m, 2H), 3.48–3.73 (m, 6H),
1324 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
4.76–3.42 (m, 4H), 4.47–4.66 (m, 4H), 4.70–4.92 (m, 8H), 1760, 1720, 1628, 1465, 1357, 1265, 1105, 930, 720; 1H NMR
5.49–6.38 (m, 4H), 7.26–7.40 (m, 20H), 7.45–7.50 (m, 6H), (400.31 MHz, CDCl3): δ 1.07 (d, J = 6.5 Hz, 3H), 2.01 (s, 3H),
7.78–7.86 (m, 8H); 13C NMR (100.67 MHz, CDCl3): δ 21.0 (2C), 2.13 (ddd, J = 14.5, 8.3, 5.5 Hz, 1H), 2.31 (ddd, J = 14.5, 8.3, 5.5
22.6 (4C), 25.0 (2C), 36.7, 36.8 (2C), 37.0, 66.5, 67.5, 67.6, 68.1, Hz, 1H), 2.38–2.56 (m, 2H), 3.62–3.70 (m, 3H), 3.77(s, 3H),
70.5, 72.1, 72.2, 73.0, 73.7, 73.8 (2C), 74.7, 75.2, 75.4, 75.6, 3.93–4.05 (m, 2H), 4.11 (dd, J = 12.9, 5.2 Hz, 1H), 4.37 (dd, J =
75.9, 77.7, 78.2, 78.5, 79.6, 82.6, 82.9, 94.3, 97.5, 126.1–126.3 10.2, 3.4 Hz, 1H), 4.50–4.81 (m, 4H), 5.05 (d, J = 4.1 Hz, 1H),
(6C), 126.9, 127.1, 127.8–128.1 (13C), 128.3–128.5 (13C), 133.2 5.14–5.36 (m, 5H), 5.66 (t, J = 6.3 Hz, 1H), 5.90 (dddd, J = 17.1,
(2C), 133.3 (2C), 135.1, 135.2, 137.7, 138.1 (2C), 138.3, 151.3, 10.4, 6.5, 5.3 Hz, 1H), 6.83 (d, J = 8.6 Hz, 1H), 7.16–7.40 (m,
151.5, 170.3 (2C); HRMS (ESI): m/z calcd for C42H44O9, [M + 8H), 7.44–7.56 (m, 3H), 7.84–8.12 (m, 6H); 13C NMR
Na]+: 715.2883; found: 715.2881.
(100.67 MHz, CDCl3): δ 16.1, 27.7, 29.7, 37.7, 55.3, 60.9, 64.5,
4.3.19. 1-O-(((1-Ethynylcyclohexyl)oxy)carbonyl)-2,3-di-O- 68.5, 69.0, 69.8, 70.1, 70.1, 72.6, 73.0, 74.0, 96.2, 96.2, 113.9,
benzyl-4-O-acetyl-6-O-tert-butyldiphenyl silyl α/β-D-galacto- 113.9, 118.3, 128.4 (4C), 128.5 (2C), 129.4, 129.4, 129.4, 129.8
pyranoside [α : β (1.0 : 2.0)] (6g). The title compound was pre- (2C), 129.9 (2C), 130.0 (2C), 130.1 (2C), 130.4, 133.3, 133.4,
pared according to the general procedures 4.2.1b, 4.2.13, 4.2.4, 133.5, 133.9, 159.4, 165.0, 165.3, 165.6, 172.4, 206.4; HRMS
4.2.14, 4.2.7, 4.2.6, 4.2.2 and 4.2.3; syrup (1.432 g, 50% yield); (ESI-MS): m/z calcd for C48H50O15, [M + Na]+: 889.3047; found:
[α]D25 (CHCl3, c 1.0): +10.4; IR (cm−1, CHCl3): 3015, 2935, 2862, 889.3042.
1725, 1615, 1458, 1366, 1260, 1117, 950, 709; 1H NMR
4.3.22. Allyl 3-O-(4-oxopentanoyl)-4-O-(2,3,4-tri-O-benzoyl-
(400.31 MHz, CDCl3): δ 1.05 (s, 9H), 1.08 (s, 9H), 1.25–1.41 (m, β-D-xylopyranosyl)-α-L-fucopyranoside (21). The title compound
2H), 1.49–1.57 (m, 2H), 1.56–1.74 (m, 8H), 1.81–1.96 (m, 4H), was prepared according to the general procedure 4.2.16; white
2.01 (s, 3H), 2.04 (s, 3H), 2.07–2.26 (m, 4H), 2.58–2.61 (m, 2H), solid (240 mg, 93% yield); mp 97.5 °C; [α]D25 (CHCl3, c 1.0):
3.59–3.90 (m, 8H), 3.88–4.25 (m, 2H), 4.47–4.87 (m, 8H), −37.4; IR (cm−1, CHCl3): 3025, 2923, 2820, 1735, 1630, 1450,
5.39–6.30 (m, 4H), 7.26–7.47 (m, 32H), 7.64–7.68 (m, 8H); 13C 1365, 1243, 1108, 936, 714; 1H NMR (400.31 MHz, CDCl3): δ
NMR (100.67 MHz, CDCl3): δ 19.2 (2C), 20.9 (2C), 22.5 (2C), 1.12 (d, J = 6.6 Hz, 3H), 2.06 (s, 3H), 2.15–2.29 (m, 1H),
22.6 (2C), 25.0, 25.1, 26.8 (2C), 26.9 (4C), 36.7–37.0 (4C), 61.1, 2.34–2.45 (m, 1H), 2.47–2.62 (m, 2H), 2.72 (s, 1H), 3.78 (dd, J =
61.5, 65.3, 67.0, 71.7, 72.2, 72.3, 73.7, 74.0, 74.7, 75.2, 75.3, 12.4, 6.0 Hz, 1H), 3.94 (dd, J = 10.0, 3.9 Hz, 1H), 4.00–4.15 (m,
75.7, 76.1, 77.8, 78.2, 78.3, 79.7, 82.6, 82.9, 94.4, 97.4, 3H), 4.22 (ddt, J = 12.8, 5.4, 1.3 Hz, 1H), 4.68 (dd, J = 12.4, 3.9
127.7–128.0 (16C), 128.1–128.6 (16C), 129.9 (3C), 130.0, 133.0 Hz, 1H), 5.03 (dd, J = 6.3, 4.3 Hz, 2H), 5.22–5.28 (m, 2H),
(2C), 133.1 (2C), 135.6, 135.7 (2C), 135.8, 137.8, 138.2 (2C), 5.29–5.37 (m, 3H), 5.73 (t, J = 6.6 Hz, 1H), 5.96 (dddd, J = 16.9,
138.3, 151.3, 151.6, 170.0, 170.1; HRMS (ESI): m/z calcd for 10.4, 6.3, 5.5 Hz, 1H), 7.32–7.39 (m, 6H), 7.47–7.56 (m, 3H),
C47H54O9Si, [M + Na]+: 813.3435; found: 813.3439.
7.94–8.04 (m, 6H); 13C NMR (100.67 MHz, CDCl3): δ 16.0, 27.6,
4.3.20. Methyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O- 29.7, 37.7, 61.0, 64.9, 67.6, 68.7, 68.9, 69.5, 69.6, 70.1, 75.7,
benzyl α/β D-galactopyranosyl) α-D-glucopyranoside [α : β 97.4, 97.6, 118.2, 128.3 (2C), 128.3 (4C), 129.1, 129.2, 129.3,
(8.0 : 1.0)] (19). The title compound was prepared according to 129.9 (4C), 130.0 (2C), 133.2, 133.4 (2C), 133.6, 164.9, 165.2,
the general procedure 4.2.15; white solid (39 mg, 95% yield); 165.5, 172.2, 206.4; HRMS (ESI): m/z calcd for C40H42O14, [M +
mp 67.4 °C; [α]D25 (CHCl3, c 1.0): +28.6; IR (cm−1, CHCl3): 3015, Na]+: 769.2472; found: 769.2473.
2965, 1730, 1510, 1445, 1365, 1215, 1095, 910, 715; 1H NMR
(400.31 MHz, CDCl3): δ 3.38–3.39 (m, 6H), 3.43–3.57 (m, 5H). phenylsilyl
4.3.23. Allyl 2-O-(2,3-di-O-benzyl-4-O-acetyl-6-O-tert-butyldi-
α-D-galactopyranosyl)-3-O-(4-oxopentanoyl)-4-O-
3.61–3.65 (m, 2H), 3.84–4.13 (m, 10H), 4.28–4.53 (m, 6H), (2,3,4-tri-O-benzoyl-β-D-xylopyranosyl)-α-L-fucopyranoside (22).
4.53–4.65 (m, 2H), 4.67–4.74 (m, 2H), 4.74–4.80 (m, 2H), The title compound was prepared according to the general pro-
4.82–4.99 (m, 7H), 5.17–5.32 (m, 4H), 5.53–6.24 (m, 4H), cedure 4.2.15; syrup (383 mg, 95% yield); [α]D25 (CHCl3, c 1.0):
7.12–7.31 (m, 26H), 7.33–7.56 (m, 32H), 7.83–8.05 (m, 12H); −78.1; IR (cm−1, CHCl3): 3280, 3025, 2930, 2855, 1752, 1486,
1
13C NMR (100.67 MHz, CDCl3): δ 55.5, 55.5, 66.7, 66.7, 68.6, 1450, 1265, 1232, 1105, 1030, 915, 710; H NMR (400.31 MHz,
68.6, 68.8, 68.8, 69.4, 69.4, 69.6, 69.6, 70.8, 70.8, 72.3, 72.3, CDCl3): δ 0.95–1.24 (m, 12H). 1.88–2.03 (m, 7H), 2.09–2.19 (m,
73.0, 73.0, 73.3, 73.3, 73.3, 73.3, 74.9, 74.9, 75.1, 75.1, 76.5, 1H), 2.27–2.45 (m, 2H), 3.50–3.77 (m, 3H), 3.89 (dd, J = 10.2,
76.5, 78.6, 78.6, 96.8, 96.9, 98.0, 104.3, 127.5–127.7 (9), 3.5 Hz, 1H), 3.93 (dd, J = 10.3, 3.5 Hz, 1H), 3.98–4.16 (m, 4H),
127.8–127.9 (8), 127.9–128.0 (8), 128.1–128.2 (14), 128.3–128.5 4.26 (t, J = 6.7 Hz, 1H), 4.52 (dd, J = 10.3, 3.2 Hz, 1H), 4.62–4.77
(14), 128.5–128.6 (6), 129.0, 129.2, 129.2, 129.2, 129.4, 129.4, (m, 3H), 4.85 (d, J = 5.8 Hz, 1H), 4.88 (d, J = 4.7 Hz, 1H),
129.8–129.8(6), 133.2, 133.2, 133.5, 133.5, 133.5, 133.5, 137.9, 4.97–5.10 (m, 3H), 5.16 (d, J = 10.3 Hz, 1H), 5.27–5.36 (m, 4H),
138.2, 138.6, 138.7, 138.8, 138.9, 139.1, 165.5, 165.7, 165.9, 5.75–5.79 (m, 2H), 5.93 (dddd, J = 16.9, 10.4, 6.3, 5.5 Hz, 1H),
165.9, 166.0, 166.3; HRMS (ESI): m/z calcd for C62H60O14, [M + 7.22–7.56 (m, 25H), 7.57–7.72 (m, 4H), 7.81–8.07 (m, 6H); 13C
Na]+: 1051.3881; found: 1051.3884.
NMR (100.67 MHz, CDCl3): δ 16.1, 19.2, 21.0, 27.0, 27.5, 27.5,
4.3.21. Allyl 2-O-(p-methoxybenzyl)-3-O-(4-oxopentanoyl)-4- 27.5, 29.7, 37.6, 62.0, 62.9, 64.6, 68.0, 68.7, 69.3, 69.7, 70.8,
O-(2,3,4-tri-O-benzoyl-β-D-xylopyranosyl)-α-L-fucopyranoside (20). 71.2, 71.3, 71.4, 72.5, 72.8, 75.5, 75.9, 76.0, 96.5, 98.1, 100.5,
The title compound was prepared according to the general pro- 117.6, 127.6–127.8 (10C), 128.4–128.5 (12C), 129.4, 129.5,
cedure 4.2.15; white solid (704 mg, 98% yield); mp 87.2 °C; 129.6, 129.9–130.1 (8C), 132.9, 133.1, 133.3, 133.3, 133.3,
[α]D25 (CHCl3, c 1.0): −74.6; IR (cm−1, CHCl3): 3014, 2930, 2849, 134.3, 135.8, 135.9, 138.5, 138.8, 165.0, 165.5, 165.6, 170.2,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1325

View Article Online
Paper
Organic & Biomolecular Chemistry
172.3, 206.2; HRMS (ESI): m/z calcd for C78H84O20Si, [M + Na]+: 2H), 4.55 (d, J = 4.3 Hz, 1H), 4.58 (d, J = 4.3 Hz, 1H), 4.64 (d, J =
1391.5223; found: 1391.5220. 13.7 Hz, 1H), 4.68 (d, J = 13.7 Hz, 1H), 4.76 (d, J = 13.7 Hz, 1H),
4.3.24. Allyl 2-O-(2,3-di-O-benzyl-4-O-acetyl-6-O-tert-butyldi- 4.89–4.92 (m, 2H), 5.16–5.24 (m, 2H), 5.24–5.29 (m, 1H), 5.32
phenylsilyl α-D-galactopyranosyl)-4-O-(2,3,4-tri-O-benzoyl-β-D- (dd, J = 17.2, 1.5 Hz, 1H), 5.38 (dd, J = 6.2, 4.7 Hz, 1H), 5.55
xylopyranosyl)-α-L-fucopyranoside (23). The title compound (dd, J = 2.9, 2.0 Hz, 1H), 5.67 (t, J = 6.4 Hz, 1H), 5.92 (dddd, J =
was prepared according to the general procedure 4.2.17; syrup 17.0, 10.3, 6.6, 5.3 Hz, 1H), 6.78 (d, J = 8.6 Hz, 2H), 7.19–7.24
(279 mg, 86% yield); [α]D25 (CHCl3, c 1.0): −112.6; IR (cm−1
,
(m, 4H), 7.25–7.39 (m, 9H), 7.40–7.50 (m, 4H), 7.51–7.60 (m,
CHCl3): 3020, 2918, 2837, 1730, 1470, 1463, 1255, 1226, 1118, 2H), 7.84–7.87 (m, 2H), 7.99–8.07(m, 6H); 13C NMR
1
1026, 917, 715; H NMR (400.31 MHz, CDCl3): δ 1.08 (s, 9H), (100.67 MHz, CDCl3): δ 16.8, 18.5, 55.3, 57.6, 61.0, 66.3, 68.4,
1.24 (d, J = 6.6 Hz, 3H), 1.93 (s, 3H), 2.58 (s, 1H), 3.55 (dd, J = 68.5, 68.7, 69.2, 70.2, 71.1, 72.7, 74.6, 75.3, 75.3, 79.2, 79.8,
12.9, 5.3 Hz, 1H), 3.58–3.68 (m, 2H), 3.80–3.87 (m, 2H), 80.5, 96.0, 98.4, 99.7, 113.8, 113.8, 118.2, 127.7, 128.3–128.5
3.88–3.98 (m, 3H), 4.03 (dd, J = 12.9, 5.8 Hz, 1H), 4.09 (dd, J = (12C), 129.4, 129.4, 129.5, 129.9–130.1 (11C), 130.3, 133.3,
10.2, 3.3 Hz, 1H), 4.22–4.27 (m, 1H), 4.30 (dd, J = 10.1, 3.1 Hz, 133.3, 133.4, 133.4, 134.1, 138.8, 159.4, 165.0, 165.5, 165.6,
1H), 4.63–4.72 (m, 2H), 4.77–4.94 (m, 4H), 4.96–5.04 (m, 2H), 166.2; HRMS (ESI): m/z calcd for C64H66O18, [M + Na]+:
5.09–5.19 (m, 3H), 5.28 (dd, J = 17.2, 1.6 Hz, 1H), 5.78 (d, J = 1145.4147; found: 1145.4142.
2.1 Hz, 1H), 5.83 (dd, J = 9.5, 7.9 Hz, 1H), 5.91 (dddd, J = 17.0,
4.3.27. Allyl
3-O-(2-O-benzoyl-3-O-methyl-4-O-benzyl-α-L-
10.3, 6.6, 5.3 Hz, 1H), 7.22–7.28 (m, 1H), 7.30–7.44 (m, 17H), rhamnopyranosyl)-4-O-(2,3,4-tri-O-benzoyl-β-D-xylopyranosyl)-
7.45–7.58 (m, 7H), 7.57–7.65 (m, 4H), 7.86–8.02 (m, 6H); 13C α-L-fucopyranoside (26). The title compound was prepared
NMR (100.67 MHz, CDCl3): δ 16.1, 19.1, 20.9, 26.9, 26.9, 26.9, according to the general procedure 4.2.16; syrup (244 mg, 88%
61.6, 63.0, 65.0, 67.7, 68.2, 68.4, 68.6, 69.4, 70.9, 72.3, 72.8, yield); [α]D25 (CHCl3, c 1.0): −98.2; IR (cm−1, CHCl3): 3039, 2935,
73.1, 73.9, 76.0, 76.0, 76.1, 97.1, 98.1, 100.6, 117.2, 127.4–127.7 1730, 1622, 1430, 1235, 1095, 1014, 970, 709; 1H NMR
(10C), 128.2–128.5 (12C), 128.8, 129.2, 129.4, 129.7–129.9 (8C), (400.31 MHz, CDCl3): δ 1.24 (d, J = 6.2 Hz, 3H), 1.30 (d, J = 6.5
132.8, 133.0, 133.3, 133.3, 133.6, 134.2, 135.7, 135.9, 138.5, Hz, 3H), 2.61 (s, 1H), 3.34–3.49 (m, 1H), 3.42 (s, 3H), 3.71–3.84
139.0, 165.4, 165.6, 165.8, 170.0; HRMS (ESI): m/z calcd for (m, 3H), 3.91–3.99 (m, 1H), 3.99–4.14 (m, 4H), 4.22 (dd, J =
C73H78O18Si, [M + Na]+: 1293.4855; found: 1293.4861.
12.9, 5.4 Hz, 1H), 4.56–4.70 (m, 2H), 4.80–4.85 (m, 2H), 5.00 (s,
4.3.25. Allyl 2-O-(p-methoxybenzyl)-4-O-(2,3,4-tri-O-benzoyl- 1H), 5.16 (d, J = 4.7 Hz, 1H), 5.20–5.30 (m, 2H), 5.30–5.39 (m,
β-D-xylopyranosyl)-α-L-fucopyranoside (24). The title compound 2H), 5.48–5.53 (m, 1H), 5.74 (t, J = 6.4 Hz, 1H), 5.95 (dddd, J =
was prepared according to the general procedure 4.2.17; white 17.0, 10.3, 6.6, 5.3 Hz, 1H), 7.09–7.21 (m, 2H), 7.26–7.39 (m,
solid (240 mg, 90% yield); mp 93.5 °C; [α]D25 (CHCl3, c 1.0): 10H), 7.42–7.46 (m, 3H), 7.49–7.56 (m, 2H), 7.81–7.83 (m, 2H),
−109.0; IR (cm−1, CHCl3): 3015, 2935, 2849, 1715, 1625, 1460, 7.97–8.03 (m, 6H); 13C NMR (100.67 MHz, CDCl3): δ 16.9, 18.0,
1355, 1260, 1102, 937, 710; 1H NMR (400.31 MHz, CDCl3): δ 57.5, 61.1, 66.7, 67.6, 68.4, 68.5, 68.8, 69.2, 69.6, 70.0, 75.3,
1.16 (d, J = 6.6 Hz, 3H), 2.48 (s, 1H), 3.59 (dd, J = 12.2, 7.0 Hz, 77.1, 79.5, 79.7, 80.4, 97.7, 98.2, 99.9, 118.2, 127.7, 128.2–128.5
1H), 3.71 (d, J = 4.3 Hz, 1H), 3.76 (s, 3H), 3.77–3.89 (m, 2H), (11C), 129.2, 129.3, 129.8–130.1 (11C), 133.2, 133.4, 133.4,
3.96 (dd, J = 13.0, 6.6 Hz, 1H), 4.09 (dd, J = 13.0, 5.2 Hz, 1H), 133.4, 133.9, 138.6, 165.2, 165.4, 165.6, 166.1; HRMS (ESI): m/z
4.14 (dd, J = 9.9, 3.1 Hz, 1H), 4.47–4.60 (m, 2H), 4.67–4.77 (m, calcd for C56H58O17, [M + Na]+: 1025.3572; found: 1025.3568.
2H), 5.02 (d, J = 5.1 Hz, 1H), 5.18 (d, J = 10.4 Hz, 1H), 5.28 (dd,
4.3.28. Allyl 2-O-(2,3-di-O-benzyl-4-O-acetyl-6-O-tert-butyldi-
J = 17.2, 1.3 Hz, 1H), 5.22–5.32 (m, 2H), 5.80 (t, J = 7.7 Hz, 1H), phenylsilyl α-D-galactopyranosyl)-3-O-(2-O-benzoyl-3-O-methyl-
5.89 (dddd, J = 17.1, 10.4, 6.5, 5.3 Hz, 1H), 6.83 (d, J = 8.6 Hz, 4-O-benzyl-α-L-rhamnopyranosyl)-4-O-(2,3,4-tri-O-benzoyl-β-D-
2H), 7.26 (d, J = 8.7 Hz, 2H), 7.28–7.43 (m, 6H), 7.46–7.54 (m, xylopyranosyl)-α-L-fucopyranoside (2). The title compound
3H), 7.96–8.00 (m, 6H); 13C NMR (100.67 MHz, CDCl3): δ 16.1, was prepared according to the general procedure 4.2.15; syrup
55.3, 61.2, 65.2, 68.3, 69.3, 69.6, 70.7, 72.2, 73.0, 74.0, 77.4, (285 mg, 91% from 5 and 320 mg, 94% yield from 26); [α]2D5
96.1, 98.6, 113.9, 113.9, 118.1, 128.5 (4C), 128.6 (2C), 129.0, (CHCl3, c 1.0): −56.3; IR (cm−1, CHCl3): 3023, 2927, 2852,
129.2, 129.3, 129.9 (6C), 130.0 (2C), 130.5, 133.5, 133.5, 133.7, 1720, 1615, 1460, 1345, 1264, 1115, 952, 709; 1H NMR
134.0, 159.4, 165.6, 165.6, 165.8; HRMS (ES): m/z calcd for (400.31 MHz, CDCl3): δ 1.01–1.15 (m, 12H), 1.32 (d, J = 6.1 Hz,
C43H44O13, [M + Na]+: 791.2680; found: 791.2683.
3H), 1.89 (s, 3H), 3.40 (s, 3H), 3.43–3.56 (m, 3H), 3.57–3.65 (m,
4.3.26. Allyl 2-O-(p-methoxybenzyl)-3-O-(2-O-benzoyl-3-O- 2H), 3.66–3.73 (m, 2H), 3.77 (dd, J = 9.4, 3.1 Hz, 1H), 3.86–3.97
methyl-4-O-benzyl-α-L-rhamnopyranosyl)-4-O-(2,3,4-tri-O-benzoyl- (m, 3H), 4.06–4.16 (m, 2H), 4.25 (t, J = 6.8 Hz, 1H), 4.31 (dd, J =
β-D-xylopyranosyl)-α-L-fucopyranoside (25). The title compound 10.1, 2.5 Hz, 1H), 4.42 (dd, J = 12.4, 4.5 Hz, 1H), 4.59–4.75 (m,
was prepared according to the general procedure 4.2.15; syrup 4H), 4.80–4.94 (m, 4H), 4.97 (d, J = 3.4 Hz, 1H), 5.01 (d, J = 3.4
(340 mg, 97% yield); [α]D25 (CHCl3, c 1.0): −62.5; IR (cm−1
,
Hz, 1H), 5.15–5.18 (m, 2H), 5.28 (dd, J = 17.2, 1.1 Hz, 1H), 5.37
CHCl3): 3068, 2927, 1715, 1610, 1440, 1247, 1108, 1027, 962, (dd, J = 8.2, 5.7 Hz, 1H), 5.50 (d, J = 5.7 Hz, 1H), 5.70 (t, J = 7.9
1
718; H NMR (400.31 MHz, CDCl3): δ 1.20 (d, J = 6.5 Hz, 3H), Hz, 1H), 5.77 (d, J = 5.7 Hz, 1H), 5.89 (dddd, J = 17.0, 10.3, 6.6,
1.38 (d, J = 6.1 Hz, 3H), 3.45 (s, 3H), 3.51 (t, J = 9.5 Hz, 1H), 5.3 Hz, 1H), 7.05–7.17 (m, 3H), 7.20–7.48 (m, 28H), 7.49–7.66
3.59 (dd, J = 12.3, 6.3 Hz, 1H), 3.71 (s, 3H), 3.72–3.74 (m, 1H), (m, 6H), 7.81–7.83 (m, 2H), 7.86–8.13 (m, 6H); 13C NMR
3.76–3.83 (m, 2H), 3.90 (dd, J = 10.3, 3.7 Hz, 1H), 4.00 (dd, J = (100.67 MHz, CDCl3): δ 16.5, 18.3, 19.2, 21.0, 27.0, 27.0, 27.0,
12.9, 6.7 Hz, 1H), 4.12 (dd, J = 13.0, 5.2 Hz, 1H), 4.17–4.27 (m, 57.5, 61.6, 62.5, 66.0, 67.6, 68.5, 68.5, 69.3, 69.5, 70.2, 71.1,
1326 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021

View Article Online
Organic & Biomolecular Chemistry
Paper
72.0, 72.6, 73.4, 73.6, 75.1, 75.3, 76.1, 77.7, 79.4, 79.9, 80.3,
98.1, 98.8, 99.9, 101.2, 116.9, 127.6–127.8 (8C), 128.1–128.5
(22C), 129.3, 129.4, 129.5, 129.7–130.1 (10C), 132.8, 133.0,
133.2, 133.2, 133.2, 133.3, 134.4, 135.8, 136.0, 138.5, 138.5,
138.8, 165.0, 165.5, 165.6, 166.2, 170.1; HRMS (ESI): m/z
2012, 23, 352; (d) F. Hempel, A. S. Bozarth, N. Lindenkamp,
A. Klingl, S. Zauner, U. Linne, A. Steinbüchel and
U. G. Maier, Microb. Cell Fact., 2011, 10, 81; (e) G. Walsh,
Nat. Biotechnol., 2010, 28, 917.
4 (a) C. De Castro, T. Klose, I. Speciale, R. Lanzett,
A. Molinaro, J. L. Van Etten and M. G. Rossmann, Proc.
Natl. Acad. Sci. U. S. A., 2018, 118, E44; (b) C. F. Quispe,
A. Esmael, O. Sonderman, M. McQuinn, I. Agarkova,
M. Battah, G. A. Duncan, D. D. Dunigan, T. P. Smith, C. De
Castro, I. Speciale, F. Ma and J. L. Van Etter, Virology, 2017,
500, 103; (c) C. De Castro, I. Speciale, G. Duncan,
D. D. Dunigan, I. Agarkova, R. Lanzetta, L. Sturiale,
A. Palmigiano, D. Garozzo, A. Molinaro, M. Tonetti and
J. L. Van Etten, Angew. Chem., Int. Ed., 2016, 55, 654–658;
(d) I. Speciale, R. Agarkova, D. D. Duncan, J. L. Van Etten
and C. De Castro, Antonie van Leeuwenhoek, 2017, 110,
1391.
calcd for
1648.6351.
C94H100O23Si, [M +
Na]+: 1648.6356; found:
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
BM and MN acknowledge the research fellowship from
CSIR-UGC-NET. SC and GW thanks IISER Pune for the fellow-
ship. SM and SH acknowledge the financial assistance from
DBT-New Delhi (BT/PR20820/MED/30/1875/2017). The authors
thank Sandip Pasari for the fruitful discussion.
5 (a) S. Lin and T. L. Lowary, Chem. – Eur. J., 2018, 24, 16992–
16996; (b) Y.-S. Wang, Y. Wu, D.-C. Xiong and X.-S. Ye,
Chin. J. Chem., 2019, 37, 42–48; (c) S. Lin and T. L. Lowary,
Org. Lett., 2020, 22, 7645–7649.
6 (a) B. Mishra, M. Neralkar and S. Hotha, Angew. Chem.,
2016, 128, 7917; (b) M. Rommel, A. Ernst and U. Koert,
Eur. J. Org. Chem., 2007, 4408.
Notes and references
1 (a) F. Piacente, M. Gaglianone, M. E. Laugieri and
M. G. Tonetti, Int. J. Mol. Sci., 2015, 16, 29315;
(b) R. Danovaro, C. Corinaldesi, A. Dell’Anno,
J. A. Fuhrman, J. J. Middelburg, R. T. Noble and
C. A. Suttle, FEMS Microbiol. Rev., 2011, 35, 993;
(c) S. Sharoni, M. Trainic, D. Schatz, Y. Lehahn,
M. J. Flores, K. D. Bidle, S. Ben-Dor, Y. Rudich, I. Koren
and A. Vardi, Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 6643;
(d) J. L. Van Etten, J. R. Gurnon, G. M. Yanai-Balser,
D. D. Dunigan and M. V. Graves, Biochim. Biophys. Acta,
2010, 1800, 152; (e) I. Barkia, N. Saari and S. R. Manning,
Mar. Drugs, 2019, 17, 304; (f) D. D. Dunigan,
L. A. Fitzgerald and J. L. Van Etten, Virus Res., 2006, 117,
119; (g) J. L. Van Etten, I. Agarkova, D. D. Dunigan,
M. Tonetti, M. C. De Castro and G. A. Duncan, Viruses,
2017, 9, 88.
7 (a) A. Imamura, A. Kimura, H. Ando, H. Ishida and
M. Kiso, Chem. – Eur. J., 2006, 12, 8862; (b) S. S. Nigudkar
and A. V. Demchenko, Chem. Sci., 2015, 6, 2687 and refer-
ences therein; (c) A. V. Demchenko, Curr. Org. Chem., 2003,
7, 35; (d) A. V. Demchenko, Synlett, 2003, 1225; (e) D. Crich,
Acc. Chem. Res., 2010, 43, 1144.
8 (a) A. Ishiwata, Y. Munemura and Y. Ito, Tetrahedron, 2008,
64, 92; (b) G. Wulff and G. Rohle, Angew. Chem., Int. Ed.
Engl., 1974, 13, 157; (c) A. V. Demchenko, T. Stauch and
G. J. Boons, Synlett, 1997, 818; (d) C. S. Chao, C. Lin,
Y. S. Mulani, W. C. Hung and K. K. Mong, Chem. – Eur. J.,
2011, 17, 12193; (e) T. Shirahata, J.-I. Matsuo, S. Teruya,
N. Hirata, T. Kurimoto, N. Akimoto, T. Sunazuka, E. Kaji
and S. Omura, Carbohydr. Res., 2010, 345, 740;
(f) G. Wasonga, Y. Zeng and X. Huang, Sci. China: Chem.,
2011, 54, 66.
2 (a) C. De Castro, A. Molinaro, F. Piacente, J. R. Gurnon,
L. Sturiale, A. Palmigiano, R. Lanzetta, M. Parrilli,
D. Garozzo, M. G. Tonetti and J. L. Van Etten, Proc. Natl.
Acad. Sci. U. S. A., 2013, 110, 13956; (b) R. H. Yolken,
L. Jones-Brando, D. D. Dunigan, G. Kannan, F. Dickerson,
E. Severance, S. Sabunciyan, C. C. Talbot Jr.,
E. Prandovszky, J. R. Gurnon, I. V. Agarkova, F. Leister,
9 (a) F. Andersson, P. Fύgedi, P. J. Garegg and M. Nashed,
Tetrahedron Lett., 1986, 27, 3919; (b) S. Manabe, Y. Ito and
T. Ogawa, Synlett, 1998, 628; (c) R. R. Schmidt and
E. Rucker, Tetrahedron Lett., 1980, 21, 1421; (d) H. Dohi,
Y. Nishida, H. Tanaka and K. Kobayashi, Synlett, 2001,
1446; (e) T. G. Frihed, M. Bols and C. M. Pedersen, Chem.
Rev., 2015, 115, 4963.
K. L. Gressitt, O. Chen, B. Deuber, F. Ma, M. V. Pletnikov 10 P. Peng and R. R. Schmidt, J. Am. Chem. Soc., 2015, 137,
and J. L. Van Etten, Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 12653.
16106; (c) M. S. Petro, I. V. Agarkova and T. M. Petro, 11 (a) J. Li, Y. Dai, W. Li, S. Laval, P. Xu and B. Yu, Asian J. Org.
J. Neuroimmunol., 2016, 297, 46.
Chem., 2015, 4, 756; (b) P. Xu, W. Xu, Y. Dai, Y. Yang and
B. Yu, Org. Chem. Front., 2014, 1, 405; (c) Y. Li, X. Yang,
Y. Liu, C. Zhu, Y. Yang and B. Yu, Chem. – Eur. J., 2010, 16,
1871; (d) Y. Ma, G. Lian, Y. Li and B. Yu, Chem. Commun.,
2011, 47, 7515; (e) Y. Zhu, Z. Shen, W. Li and B. Yu, Org.
Biomol. Chem., 2016, 14, 1536.
3 (a) P. Spolaore, C. Joannis-Cassan, E. Duran and
A. Isambert, J. Biosci. Bioeng., 2006, 101, 87–96; (b) S. Sasso,
G. Pohnert, M. Lohr, M. Mittag and C. Hertweck, FEMS
Microbiol. Rev., 2012, 36, 761; (c) S. S. Merchant, J. Kropat,
B. Liu, J. Shaw and J. Warakanont, Curr. Opin. Biotechnol.,
This journal is © The Royal Society of Chemistry 2021
Org. Biomol. Chem., 2021, 19, 1315–1328 | 1327

View Article Online
Paper
Organic & Biomolecular Chemistry
12 (a) B. Fraser-Reid, K. N. Jayaprakash, J. C. López,
A. M. Gómez and C. Uriel, in ACS Symp. Ser. (Frontiers in
Modern Carbohydrate Chemistry), ed. A. V. Demchenko,
Oxford Univ. Press, 2007, vol. 960, pp. 91–117;
(b) T. Ishikawa and H. G. Fletcher, J. Org. Chem., 1969, 34,
563; (c) R. Eby and C. Schuerch, Carbohydr. Res., 1974, 34,
79 and references therein; (d) T. Mukaiyama, M. Suenaga,
H. Chiba and H. Jona, Chem. Lett., 2002, 56;
921; (h) B. S. Komarova, M. V. Orekhova, Y. E. Tsvetkov and
N. E. Nifantiev, Carbohydr. Res., 2014, 384, 70; (i) D. Crich
and W. Cai, J. Org. Chem., 1999, 64, 4926; ( j) D. Crich and
N. S. Chandrasekera, Angew. Chem., Int. Ed., 2004, 43, 5386;
(k) A. Imamura, H. Ando, H. Ishida and M. Kiso, Org. Lett.,
2005, 7, 4415; (l) A. Imamura, N. Matsuzawa, S. Sakai,
T. Udagawa, S. Nakashima, H. Ando, H. Ishida and
M. Kiso, J. Org. Chem., 2016, 81, 9086.
(e) A. V. Demchenko, E. Rousson and G. J. Boons, 13 (a) E. J. Corey and P. Carpino, J. Am. Chem. Soc., 1989, 111,
Tetrahedron Lett., 1999, 40, 6523; (f) M. Takatani, I. Matsuo
and Y. Ito, Carbohydr. Res., 2003, 338, 1073;
(g) N. Ustyuzhanina, B. Komarova, N. Zlotina, V. Krylov,
5472; (b) A. G. Gerbst, N. E. Ustuzhanina, A. A. Grachev,
D. E. Tsvetkov, E. A. Khatuntseva and N. E. Nifantiev,
Mendeleev Commun., 1999, 114–116.
A. G. Gerbst, Y. Tsvetkov and N. E. Nifantiev, Synlett, 2006, 14 See the ESI.†
1328 | Org. Biomol. Chem., 2021, 19, 1315–1328
This journal is © The Royal Society of Chemistry 2021