Nucleofuge Generating Glycosidations by the Remote Activation of Hydroxybenzotriazolyl Glycosides

Article abstract of DOI:10.1021/acs.joc.7b02027

Hydroxybenzotriazole is routinely used in peptide chemistry for reducing racemization due to the increased reactivity. In this article, very stable hydroxybenzotriazolyl glucosides were identified to undergo glycosidation. The reaction was hypothesized to go through the remote activation by the Tf₂O at the N3-site of HOBt followed by the extrusion of the oxocarbenium ion that was attacked by the glycosyl acceptor. Further, equilibration of the zwitterionic benzotriazolyl species makes the leaving group noncompetitive and generates the nucleofuge that has been reconverted to the glycosyl donor. The reaction is mild, high yielding, fast and suitable for donors containing both C2-ethers and C2-esters as well. The regenerative-donor glycosidation strategy is promising as it enables us to regenerate the glycosyl donor for further utilization. The utility of the methodology for the oligosaccharide synthesis was demonstrated by the successful synthesis of the branched pentamannan core of the HIV1-gp120 complex.

Full text of DOI:10.1021/acs.joc.7b02027

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Article
Nucleofuge Generating Glycosidations by the Remote
Activation of Hydroxybenzotriazolyl Glycosides
Mahesh Neralkar, Bijoyananda Mishra, and Srinivas Hotha
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02027 • Publication Date (Web): 06 Oct 2017
Downloaded from http://pubs.acs.org on October 8, 2017
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Nucleofuge Generating Glycosidations by the Remote Activation of
Hydroxybenzotriazolyl Glycosides
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Mahesh Neralkar, Bijoyananda Mishra and Srinivas Hotha*
Department of Chemistry, Indian Institute of Science Education and Research, Pune –
411 008, MH, India
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s.hotha@iiserpune.ac.in
Abstract
Hydroxybenzotriazole is routinely used in peptide chemistry for reducing racemization
due to the increased reactivity. In this manuscript, very stable hydroxybenzotriazolyl
glucosides were identified to undergo glycosidation. The reaction was hypothesized to
go through the remote activation by the Tf2O at the N3ꢀsite of HOBt followed by the
extrusion of the oxocarbenium ion that was attacked by the glycosyl acceptor. Further,
equilibration of the zwitterionic benzotriazolyl species makes the leaving group nonꢀ
competitive and generates the nucleofuge that has been reconverted to the glycosyl
donor. The reaction is mild, high yielding, fast and suitable for donors containing both
C2ꢀethers and C2ꢀesters as well. The regenerativeꢀdonor glycosidation strategy is
promising as it enables us to regenerate the glycosyl donor for further utilization. The
utility of the methodology for the oligosaccharide synthesis was demonstrated by the
successful synthesis of the branched pentamannan core of the HIV1ꢀgp120 complex.
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Introduction
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Burgeoning growth in all the allied fields of Glycosciences led to the identification of
myriad roles played by glycoconjugates and oligosaccharides in many physiological and
pathological processes.1,2 A major impediment holding the exponential growth of the
Glycosciences is the lack of pure, well characterized and homogenous oligosaccharides
or glycoconjugates.3 Isolating oligosaccharides from natural sources is a challenging
task since they exist in tiny quantities as microꢀheterogeneous forms.3 Often, totally
chemical4 or chemoenzymatic5 syntheses are the most popular strategies for obtaining
sufficient quantity of oligosaccharides using a bottomsꢀup approach, wherein saccharide
residues are sequentially condensed by a glycosidation reaction.3 The glycosidation
reaction involves two partners termed as glycosyl donor and glycosyl acceptor.4 The
glycosyl donor often contains a nucleofuge at the anomeric carbon which generates an
oxocarbenium ion intermediate that will be attacked by the glycosyl acceptor upon the
activation by a promoter. Several decades of research culminated into the development
of numerous glycosyl donors’ viz. glycosyl halides,6ꢀ8 esters,9 phosphates,10 imidates,11
carbonates,12 thioglycosides,13 selenyl glycosides,14 glycals,15 hemiacetals,16,17 alkenyl18
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and alkynyl19 glycosides.4
BnO
BnO
OBn
BnO
BnO
PHN
O
OBn
R
O
BnO
OH
N
N
O
N
N
O
N
N
O
BnO
O
N
N
N
HOBt (1)
PeptideꢀHOBt (2)
Glucosyl Donor (3)
SugarꢀHOBt (4)
Figure 1. Structures of Hydroxybenzotriazole (HOBt) and PeptideꢀHOBt and SugarꢀHOBt
Propargyl glycosides are observed to undergo glycosidation in the presence of catalytic
amount of gold(III) halides in CH2Cl2 at 70 ⁰C.19 They undergo glycosidation when Cꢀ2
position is protected as a benzyl ether only.19 Enhanced reactivity by the addition of
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hydroxybenzotriazole (HOBt) (1) is well documented in the peptide chemistry through the
formation of activated ester 2 (Figure 1).20 In this premise, addition of HOBt in the goldꢀ
catalysed glycosidation was hypothesized to further increase the overall turnover number
(TON) of the goldꢀcatalysed glycosidation (Scheme 1).
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Scheme 1. Synthesis of HOBt glycosides.
Results and Discussion
Accordingly, donor 3 was treated with SugꢀOH (5) and HOBt (1, 1.0 eq.) and catalytic
amount of AuCl3 in the presence of 4Å MS powder at 70 ⁰C for 24 h. To our surprise, the
required disaccharide 6 was not noticed; instead HOBt glucoside 4 (6%) was observed
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as the sole product that can be rationalized by the participation of the HOBt as the
glycosyl acceptor. HOBtꢀglucoside 4 is easily accessible from pentenyl glucoside 7 via
glucosyl bromide 8 in 80% over two steps (Scheme 1).21
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Glucoside 4 is quite a stable compound; however, transformed partially (~10%) to the
corresponding hemiacetal at 25 ⁰C over 6 months. Alternately, very stable perꢀOꢀ
benzoyl HOBtꢀglucoside (10) was conveniently synthesized from perꢀOꢀbenzoyl
bromoside (9) in high yield. Compound 10 was found to be very stable at 25 ⁰C for
more than 6 months. In fact, we were able to grow single crystals in MeOH by slow
evaporation method. The single crystal diffraction studies further confirmed the Oꢀ
glycosidic linkage between the HOBt and the glycan moiety along with the overall
structural integrity of the HOBtꢀglucoside 10. Similar results were observed while
synthesizing HOBt glycosides of Manpꢀ (11, 12), Galpꢀ (13) and GlcNTrocꢀ (14).
Remarkable stability of these HOBtꢀglycosides intrigued us and encouraged us to
investigate their further utility as glycosyl donors (Scheme 2).
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Scheme 2. HOBt glycosides as glycosyl donors. MS = 4Å Molecular Sieves powder
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Stability of the glucoside 4 and our interest in the development of stable glycosyl donors
emboldened us to study its further utility for glycosylation. To begin the exploration,
HOBtꢀglucoside 4 was treated with a model glucoseꢀderived alcohol 5 in the presence of
a molar equivalent of various Lewis and Brønsted acids (Scheme 2). Chemical
glycosidation did not occur with BF3·Et2O at 25 ⁰C; however, Lewis acids which can
produce Brønsted acids (HCl or TfOH) such as AuCl3, Cu(OTf)2, Sc(OTf)3 and TMSOTf
afforded the desired disaccharide 6 in 5ꢀ10% yield. No reaction was observed with 1
equivalent of TfOH presumably due to the neutralization of TfOH by the HOBt moiety.
Diminished yields through the activation of the exocyclic C1ꢀoxygen diverted our
attention to the activation through the triazole moiety. Earlier independent investigations
by Hanessian23 and Woerpel24 groups suggested that N3ꢀnitrogen of the triazole moiety
can be alkylated by MeOTf. Hence, GlcpꢀHOBt (4) was treated with MeOTf to observe
no glycosidation. Nevertheless, addition of a molar equivalent of Tf2O afforded the
required disaccharide 6 in 90% yield as α,βꢀmixture (3.5:1.0). Almost or similar yield of
disaccharide 6 was observed with 0.5 or 0.4 equivalents of Tf2O. Further decrease in
Tf2O equivalents was noticed to diminish the overall performance (Scheme 2).
Optimized reaction conditions were observed to be suitable for synthesizing even a Cꢀ
glucoside 16 in the presence of Tf2O (0.4 eq.) and allyl trimethylsilane (8.0 eq.).
Similarly, the protocol afforded the azido glucoside 17 (α:β = 9:1) in the presence of
TMSN3 and 0.4 equivalents of Tf2O at 0 ⁰C (Scheme 2).
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Mechanistically, one can hypothesize that electron push from the endocyclic oxygen of
the donor due to the remote activation of the N3ꢀnitrogen of the triazole moiety can lead
to the formation of the oxocarbenium ion A and a Zwitterionic species B along with TfOꢀ
(Figure 2). The TfOꢀ can regenerate Tf2O and another intermediate D.22 Acceptor ROH
can attack on the oxocarbenium (R = ꢀCH2Ph) in a nonꢀdiastereoselective fashion to give
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Figure 2. Plausible mechanism for the HOBt activation
α,βꢀmixture of glycosides or result in a 1,2ꢀtrans glycoside through trioxolenium ion C if
the oxocarbenium ion A is stabilized with groups such as esters (ꢀOBz). Hydrolysis of
HOBt glycoside was noticed to afford the corresponding hemiacetal and trace amount of
ROTf if the Tf2O was introduced prior to the addition of acceptor ROH. Equilibration29 of
species D to HOBt (1) is important because it makes the leaving group a nonꢀcompeting
nucleophile.25ꢀ29 Minute variation in reaction time was observed with individual anomers
of the donor 4 without any significance on the net stereochemical outcome of the
disaccharide 6. The regeneration of the nucleofuge was further investigated by UPLCꢀ
MS studies (Figure 3). The glycosylation reaction of 10+5 showed generation of the
nucleofuge 1 along with the disaccharide 24. Furthermore, thus generated HOBt (1) was
treated with glucosyl bromide 9 to regenerate the glucosyl donor 10 (Figure 3).
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Figure 3. Regeneration of the nucleofuge (1) and the donor (10)
Donorꢀregenerative glycosidations is an emerging trend in the chemical glycosidation
field. The concept has been investigated by Demchenko30 using –OFox imidate donors,
by Wan31 through an interrupted Pummerer reaction using 2ꢀ(2ꢀpropylthiol)benzyl (PTB)
glycosides and by Jensen32 utilizing oꢀmethoxybenzoates.
Further, a panel of diverse glycosyl donors (4, 10ꢀ15) derived from various aldoses were
explored for the glycoside synthesis using a set of glycosyl acceptors (18ꢀ22) to obtain
glycosides and disaccharides (24ꢀ39) in very high yield (Scheme 3). Notably, routinely
used protecting groups such as benzyl ethers, benzoates, acetates and Trocꢀ were well
tolerated under the reaction conditions. It has been identified that diastereomeric
products were obtained whenever the Cꢀ2 position was occupied by a benzyl ether and
only 1,2ꢀtrans diastereomer was noticed when the Cꢀ2 position has an ester (Scheme
3).20
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Scheme 3. HOBt glycosides as glycosyl donors for the synthesis of glycosides and
saccharides
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In continuation, the nuance of the just developed HOBt glycosyl donors is demonstrated
by the successful synthesis of core pentamannan that is a constituent of the HIV1ꢀGP120
complex.33ꢀ35 Synthesis of pentamannan was envisioned from the monosaccharide
building block containing two free hydroxyl groups so that one can realize a trisaccharide
in a {2x1+1} fashion and almost similar strategy ({2x1+3}) can be applied to realize the
pentamannan.
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1)Bu2SnO, MeOH
HO
HO
HO
HO
HO
O
TBDPSO
90 oC, 2 h
OH
O
TBDPSCl, Imidazole
OH
OH
O
O
HO
O
2)AllylBr, Bu4N+Iꢀ
DMF, 0 oC, DMF
78%, 9 h
Toluene, 70 0
C
OMe
OMe
OMe
40%, 24 h over 2 steps
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41
42
BnBr, NaH,
DMF, 0 o
C
6 h, 81%
HF.Pyridine
THF:Py (5:1), 0 o
HO
BnO
HO
HO
TBDPSO
OBn
O
OBn
O
15mol% PdCl2
OBn
O
BnO
BnO
O
MeOH: CH2Cl2 (1:1)
3 h, 71%
C
O
3 h, 81%
OMe
OMe
OMe
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44
43
OBz
O
BnO
BnO
BnO
BnO
OBz
O
BnO
BnO
BnO
OBz
BnO
45
a) Br2, CH2Cl2, ꢀ10
C
O
BnO
O
OBn
4Å MS powder, 20 min
O
Tf2O, 4Å MS powder
CH2Cl2, 0 o
O
BnO
N
N
O
O
N
C
b) Et3N, HOBt, CH2Cl2, 2 h
73% over two steps
O
BzO
OCH3
30 min, 83%
4636
47
48
BnO OBn
OBn
NaOMe, MeOH
25 oC, 1 h, 95%
OH
O
HO
HO
HO
OBz
O
BzO
OH
O
BzO
BnO
BzO
O
BnO
HO
BnO
O
HO
O
a) NaOMe, MeOH
25 oC, 5 h
BnO
BnO
BnO
HO
O
OBn
O
O
11
BnO
O
OH
O
O
HO
b) 10% Pd/C, H2
MeOHꢀEtOAc(1:1), 48 h
Tf2O, 4Å MS powder
CH2Cl2, 0 o
30 min, 72%
O
O
OBn
O
HO
OCH3
O
O
BnO
C
O
O
OCH3
80% over two steps
O
O
HO
BnO OBn
OBn
O
OCH3
O
HO
OH
OH
BzO
BzO
HO
49
OH
OH
BnO
OBn
OBn
51
50
OBz
OBz
Scheme 4. Synthesis of branched pentamannan core of HIVꢀ1ꢀGP120.
Our endeavour started with the wellꢀknown methyl αꢀ ꢀmannopyranoside (40) which has
D
converted into the aglycon 45 in five steps through compounds 41ꢀ44. The glycosyl
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donor 47 was easily obtained from nꢀpentenyl mannopyranoside 4636 in high yield
following the aforementioned procedure through mannosyl bromide intermediate. The
HOBtꢀmediated glycosidation between diol 45 and 2.2 equivalents of donor 47 was
triumphantly achieved in the presence of Tf2O (0.4 eq.), 4Å MS powder, CH2Cl2, at 0 ⁰C
for 20 min to afford the trisaccharide 48 in very high yield. Saponification followed by
glycosidation with 2.2 equivalents of donor 11 afforded the pentamannan 50 which is part
of the HIVꢀ1 GP120 complex. Ester hydrolysis under Zemplén conditions
(NaOMe/MeOH/25 ⁰C/0.5 h) followed by hydrogenolysis (PdꢀC/H2/MeOH/25 ⁰C/24 h)
afforded the fully deprotected pentamannan 51 as a methyl glycoside (Scheme 4).22
Conclusions
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In summary, hydroxybenzotriazolyl glycosides were identified as stable glycosyl
donors that are well suited for the expedient synthesis of glycosides, azidoꢀglycosides, Cꢀ
glycosides and oligosaccharides under mild reaction conditions. Glycosidation with
HOBtꢀglycosides hypothesized to occur by the remote activation of the N3ꢀnitrogen of the
benzotriazole in the presence of subꢀstoichiometric amounts of Tf2O. The glycosidation
occurs with both armed as well as disarmed glycosyl donors. Regenerativeꢀdonor
glycosidation approach is promising as it enables us to regenerate the glycosyl donor for
further utilization. Utility of the HOBtꢀmediated glycosidation for the oligosaccharide
synthesis was demonstrated by the successful convergent synthesis of branched
pentamannan core of the HIV1ꢀgp120 complex.
Experimental Section
General Methods:
Unless otherwise noted, materials were obtained from SigmaꢀAldrich and were used
without further purification. Unless otherwise reported all reactions were performed under
Nitrogen atmosphere. Removal of solvent in vacuo refers to distillation using a rotary
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evaporator attached to an efficient vacuum pump. Products obtained as solids or syrups
were dried under high vacuum. MS powder means flame dried and freshly powdered 4Å
molecular sieves. Analytical thinꢀlayer chromatography was performed on preꢀcoated
silica plates (F254, 0.25 mm thickness); compounds were visualized by UV light or by
staining with anisaldehyde spray. Optical rotations were measured on a digital
polarimeter. IR spectra were recorded on a FTꢀIR spectrometer. NMR spectra were
recorded either on a 400 or a 500 MHz with CDCl3 or CD3OD as the solvent and TMS as
the internal standard. High resolution mass spectroscopy (HRMS) was performed using
an ESIꢀTOF mass analyser. Low resolution mass spectroscopy (LRMS) was performed
on UPLCꢀMS with TLC interface.
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(A) General Experimental Procedure for the Synthesis of Hydroxylbenzotriazolyl
Glycosyl Donors: From Glycosyl Bromide with Et3N as base: Glycosyl bromide (9)
(500 mg, 758 ꢁmol, 1 eq.) in dry CH2Cl2 (5 mL) was stirred under nitrogen atmosphere
for 5 min. Solid HOBt 1 (113 mg, 834 ꢁmol, 1.1 eq.) was added and followed by Et3N (53
ꢁL, 3.79 mmol, 5 eq.). The resulting reaction mixture was stirred for 2 h at 25 oC. At the
end of the reaction as adjudged by TLC examination, the reaction mixture was
concentrated in vacuo.
The crude residue was purified by silica gel column
chromatography to afford corresponding glycosyl donor 10 (510 mg, 92%) as white solid.
From Glycosyl Bromide with Ag2CO3 as base: Glycosyl bromide 9 (500mg, 758 ꢁmol,
1 eq.) in dry CH2Cl2 (5 mL) was stirred under nitrogen atmosphere for 5 min. Solid HOBt
(113 mg, 834 ꢁmol, 1.1 eq.) followed by Ag2CO3 (209 mg, 758 ꢁmol, 1 eq.) were added
0
and refluxed for 2 h at 40 C. The reaction mixture was filtered through a pad of celite
and the filtrate was concentrated in vacuo. The residue was purified by silica gel column
chromatography to afford corresponding glycosyl donor 10 (421 mg, 79%).
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From Glycosyl Bromide with Phase Transfer Catalyst: Solid HOBt 9 (113 mg, 834
ꢁmol, 1.1 eq.) was dissolved in 2.5 mL of 1N solution of aqueous NaHCO3. In another 25
mL round bottom flask, the glycosyl bromide 9 (500 mg, 758 ꢁmol, 1 eq) was dissolved
anhydrous CH2Cl2 (5 mL) was stirred under nitrogen for 5 min followed by addition of
tetrabutylammonium hydrogensulphate (TBAHS) (276 mg, 1.14 mmol, 1.5 eq) as a
phase transfer catalyst. 1N Solution of NaHCO3 containing HOBt was added and
resulting reaction mixture was stirred for 8 h. The reaction mixture was washed with 250
mL of water and organic phase was separated and was dried over Sodium sulphate and
concentrated in vacuo. The resulting residue was purified by silica gel column
chromatography to afford glycosyl donor 10 (450 mg, 84%).
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(B) General Procedure for conversion of pent-4-enyl glycosides to glycosyl
bromosides: Pentꢀ4ꢀenyl glucoside (7) (1.0 g, 1.64 mmol, 1 eq.) in dry CH2Cl2 (10 mL)
0
containing 4Å molecular sieves powder (0.5 g) was cooled to ꢀ10 C under nitrogen
atmosphere. Molecular bromine (130 ꢁL, 2.46 ꢁmol, 1.5 eq.) in CH2Cl2 (1 mL) was
0
added drop wise to the reaction mixture and stirred at ꢀ10 C for additional 10 minutes.
The reaction mixture was concentrated under reduced pressure to afford 2,3,4,6ꢀtetraꢀOꢀ
benzyl glycopyranosyl bromide as solid along with 4Å molecular sieves powder which
was immediately used in next step without any additional purification using
aforementioned procedure.
(C) General Procedure for Glycosylation: A solution of glycosyl donor 10 (50 mg, 70
ꢁmol, 1 eq) and glycosyl acceptor 5 (39 mg, 77 ꢁmol, 1.1 eq.) in dry CH2Cl2 (2.5 mL) in
the presence of 4Å molecular sieves (25 mg) was stirred for 15 min at 0 oC under N2 atm.
Tf2O (5 ꢁL, 28 ꢁmol, 0.4 eq) dissolved in 0.5 mL of CH2Cl2 was added at 0 oC and stirred
for 30 min. The reaction was quenched by the addition of Et3N (300 ꢁL) and stirred for
additional 15 min and filtered through a pad of celite, concentrated in vacuo and the
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resulting residue was purified by silica gel column chromatography to afford discharide
23 (65 mg, 86%) as a white solid.
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(D) Synthesis of Compound 45: To a solution of compound 40 (5.00 g, 25.75 mmol, 1
eq) in 250 mL of MeOH, Bu2SnO (6.41 g, 25.75 mmol, 1 eq) was added and refluxed for
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O
2 h at 90 C. After two hours, methanol was completely evaporated under diminished
pressure. The crude residue was redissolved in toluene (200 mL) and allyl bromide
(17.80 mL, 206 mmol, 8 eq) and TBAI (4.7 g, 12.87 mmol, 0.5 eq) were added. The
o
reaction mixture heated at 70 C for 24 h. Solvent was evaporated under diminished
pressure and the resulting residue was separated by silica gel column chromatography
using CH2Cl2 and methanol as mobile phase to afford 41 (2.5 g, 40 %) as a white solid.
Compound 41 (2.40 g, 10.25 mmol, 1eq) was dissolved in 25 mL dry DMF solvent and
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cooled to 0 C, imidazole (697 mg, 10.25 mmol, 1 eq) was added and stirred for 30 min
o
o
at 0 C followed by addition of TBDPSCl (2.39 mL, 9.22 mmol, 0.9 eq) at 0 C and
reaction mixture was stirred at 25 oC for 12 h. The reaction mixture was diluted with ethyl
acetate (50 mL) and washed with brine solution and ethyl acetate (3x50 ml). The organic
layer was separated and dried over anhydrous Na2SO4. The organic solvent was
evaporated under vacuum and the crude residue was purified by silica gel column
chromatography to afford 42 (3.8 g, 78%) as a thick syrup.
Compound 42 (3.50 g, 7.41 mmol, 1 eq) dissolved in 35 mL of dry DMF was cooled to 0
oC and sodium hydride (711 mg, 29.62 mmol, 4 eq) was added and stirred for 30 min at 0
oC. Benzyl bromide (2.64 mL, 22.00 mmol, 3 eq) was added and stirred for 6 h at 25 oC.
The reaction mixture was diluted with water and washed ethyl acetate (3x40 mL) and
combined organic layers were washed with brine solution. The organic layer was
separated, dried (Na2SO4) and concentrated in vacuo to obtain a residue that was
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purified by the silica gel column chromatography using ethyl acetate and nꢀhexane as
mobile phase to afford 43 (4.1 g, 81%) as a thick syrup.
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To a solution of silyl ether 43 (3.50 g, 5.36 mmol) in 40 mL of THF:Py (5:1) was added
HF—Py (3 mL) at 0 ⁰C, allowed to warm to 25 ⁰C and stirred for 3 h. The reaction mixture
was concentrated in vacuo to obtain a residue which was purified by silica gel column
chromatography (ethyl acetate and nꢀhexane) to afford 44 ( 2.21 g, 81% yield).
Compound 44 (1.60 g, 3.86 mmol) was dissolved in 100 mL of dry methanol:CH2Cl2 (1:1)
and PdCl2 (102 mg, 579 ꢁmol, 0.15 Eq.) dissolved in 5 mL methanol was added
dropwise. The reaction mixture was stirred for additional 3 h at 25 oC and quenched with
Et3N and filtered through celite. The filtrate was concentrated in vacuo and the resulting
residue was purified by silica gel column chromatography to afford compound 45 (1.5 g,
71%) as a pale yellow syrup.
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(E) Synthesis of Compound 47: Pentꢀ4ꢀenyl mannopyranoside (46) (1.20 g, 1.93
mmol, 1 eq.) in dry CH2Cl2 (12 mL) containing 4Å molecular sieves powder (0.6 g) was
cooled to ꢀ10 0C under nitrogen atmosphere. Molecular bromine (154 ꢁL, 2.89 mmol, 1.5
0
eq.) in CH2Cl2 (1 mL) was added drop wise to the reaction mixture and stirred at ꢀ10 C
for additional 10 minutes. The reaction mixture was concentrated under reduced
pressure to afford mannopyranosyl bromide that was immediately redissolved in dry
CH2Cl2 (10 mL) was stirred under nitrogen atmosphere for 5 min. Solid HOBt (1) (265
mg, 1.96 mmol, 1.1 eq.) was added and followed by Et3N (124 ꢁL, 8.91 mmol, 5 eq.).
The resulting reaction mixture was stirred for 2 h at 25 oC. At the end of the reaction as
adjudged by TLC examination, the reaction mixture was concentrated in vacuo. The
crude residue was purified by silica gel column chromatography to afford corresponding
glycosyl donor 47 (927 mg, 73%) as a thick syrup.
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(F) Synthesis of Compound 48: A solution of glycosyl donor 47 (500 mg, 744 ꢁmol, 1
eq) and glycosyl acceptor 45 (140 mg, 372 ꢁmol, 0.5 eq.) in dry CH2Cl2 (10 mL) in the
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presence of 4Å molecular sieves (50mg) was stirred for 15 min at 0 C under N2 atm.
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Tf2O (50 ꢁL, 297 ꢁmol, 0.4 eq) dissolved in 0.5 mL of CH2Cl2 was added at 0 C and
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stirred for 30 min. The reaction was quenched by the addition of Et3N (1 mL) and stirred
for additional 15 min and filtered through a pad of celite, concentrated in vacuo and the
resulting residue was purified by silica gel column chromatography to afford trisaccharide
48 (902 mg, 83%).
(G) Synthesis of compound 49: To a solution of trisaccharide 48 (850 mg, 587 ꢁmol)
methanolꢀCH2Cl2 (1:1) (8 mL) and freshly prepared NaOMe (12.69 mg, 234 ꢁmol) was
added and stirred for 1 h. The NaOMe was quenched with Amberlite IRꢀ120 and filtered,
the filtrate was concentrated in vacuo. The crude residue was purified by silica gel
column chromatography to afford trisaccharide 49 (670 mg, 95%).
(H) Synthesis of compound 50: A solution of glycosyl donor 11 (500 mg, 700 ꢁmol, 1.0
eq) and glycosyl acceptor 49 (434 mg, 350 ꢁmol, 0.5 eq.) in dry CH2Cl2 (10 mL) in the
o
presence of 4Å molecular sieves (200 mg) was stirred for 15 min at 0 C under N2 atm.
o
Tf2O (47 ꢁL, 280 ꢁmol, 0.4 eq) dissolved in 1 mL of CH2Cl2 was added at 0 C and
stirred for 30 min. The reaction was quenched by the addition of Et3N (1 mL) and stirred
for additional 15 min and filtered through a pad of celite, concentrated in vacuo and the
resulting residue was purified by silica gel column chromatography to afford
pentasaccharide 50 (1.10 g, 72%).
(I) Synthesis of compound 51: To a solution of compound 50 (1.00 g, 417 ꢁmol, 1eq)
methanolꢀCH2Cl2 (1:1) (7 mL), a 1M solution of NaOMe in MeOH (1 mL) was added and
stirred for 5 h. The NaOMe was quenched by Amberlite IRꢀ120, filtered, and
concentrated in vacuo and the residue was directly carried forward for hydrogenolysis
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without further purification. The crude residue was redissolved in a 1:1 mixture of
methanol and ethyl acetate (5 mL), 10% Pd/C (15 mg) was added and stirred vigorously
for 48 h under H2 atmosphere (balloon). The reaction mixture was filtered through a pad
of Celite®, the filtrate was concentrated in vacuo. The residue was purified by BIOꢀRAD
BioꢀGel Pꢀ4 Gel using distilled water as mobile phase. The compound 51 (320 mg, 80%)
was obtained by lyophilization.
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1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀylꢀ2,3,4,6ꢀtetraꢀOꢀbenzylꢀβꢀDꢀglucopyranoside (4): Eluent for
purification: 15% ethyl acetate in nꢀhexane; white solid; yield 983 mg (80%); mp 124 oC;
25
[α]D +30.5 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3034, 2912, 1454, 1362; 1H NMR (399.78
MHz, CDCl3): δ 3.47 (d, J = 3.7 Hz, 1H), 3.57 – 3.65 (m, 1H), 3.71 (dd, J = 11.0, 4.1 Hz,
1H), 3.77 – 3.88 (m, 2H), 3.93 (t, J = 8.3 Hz, 1H), 4.38 – 4.58 (m, 2H), 4.64 (d, J = 10.9
Hz, 1H), 4.89 (dd, J = 11.0, 2.5 Hz, 2H), 4.94 (d, J = 10.8 Hz, 1H), 5.02 (d, J = 10.9 Hz,
1H), 5.26 (d, J = 10.7 Hz, 1H), 5.40 (d, J = 7.9 Hz, 1H), 7.19 – 7.48 (m, 20H), 7.54 (d, J =
6.6 Hz, 2H), 7.76 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H); 13C NMR (100.67 MHz,
CDCl3): δ 68.4, 73.6, 75.1, 75.3, 75.4, 75.9, 76.9, 80.2, 84.4, 109.3, 110.3, 119.9, 124.7,
127.6, 127.6, 127.7, 127.8, 127.8, 127.9, 127.9, 127.9, 128.0, 128.0, 128.0, 128.0, 128.4,
128.4, 128.5, 128.5, 128.5, 128.5,128.6, 128.6, 128.6, 129.1, 137.7, 137.9, 137.9, 138.3,
143.5; HRMS (ESIꢀMS): m/z calcd for [C40H39N3O6Na+]: 680.2737; Found: 680.2737.
Methyl
2,3,4ꢀtriꢀOꢀbenzoylꢀ6ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzylꢀα/βꢀDꢀglucopyranosyl)ꢀαꢀDꢀ
glucopyranoside (6): Eluent for purification: 20% ethyl acetate in nꢀhexane; Pale yellow
o
solid; yield 70 mg (90%); mp 55 C; [α]D25 +52.2 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3031,
2929, 1730, 1600; 1H NMR (399.78 MHz, CDCl3): δ 3.44 (d, J = 22.8 Hz, 6H), 3.56 (ddd,
J = 18.6, 10.3, 2.8 Hz, 4H), 3.61 – 3.94 (m, 10H), 4.01 (t, J = 9.3 Hz, 2H), 4.32 – 4.54 (m,
6H), 4.54 – 4.70 (m, 14H), 4.71 – 5.13 (m, 4H), 5.58 (s, 2H), 6.19 (s, 2H), 7.16 – 7.45 (m,
54H), 7.48 – 7.57 (m, 4H), 7.84 – 7.93 (m, 4H), 7.95 – 8.07 (m, 8H);13C NMR (100.67
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MHz, CDCl3): δ 55.6, 55.7, 66.7, 68.3, 68.6, 68.7, 68.9, 69.1, 69.7, 70.0, 70.3, 70.6, 70.7,
72.2, 72.3, 73.2, 73.5, 73.5, 74.9, 75.0, 75.1, 75.6, 75.8, 77.4, 77.7, 80.0, 81.8, 82.4,
84.6, 96.8, 96.9, 97.3, 104.1, 127.6, 127.6, 127.6, 127.7, 127.7, 127.7, 127.7, 127.7,
127.7, 127.7, 127.7, 127.8, 127.9, 128.0, 128.0, 128.0, 128.0, 128.0, 128.0, 128.0, 128.0,
128.1, 128.1, 128.1, 128.3, 128.3, 128.3, 128.3, 128.3, 128.3, 128.3, 128.4, 128.4, 128.4,
128.4, 128.4, 128.4, 128.4, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5,
128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 129.0, 129.1, 129.1, 129.2, 129.3, 129.3,
129.7, 129.7, 129.7, 129.8, 130.0, 130.0, 130.0, 130.0, 130.0, 130.0, 130.0, 130.0, 133.1,
133.2, 133.4, 133.4, 133.4, 133.5, 138.0, 138.1, 138.2, 138.5, 138.5, 138.6, 138.7, 138.9,
165.3, 165.5, 165.8, 165.9, 165.9, 165.9; HRMS (ESIꢀMS): m/z calcd for
[C62H60O14Na+]:1051.3881; Found: 1051.3877.
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1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2,3,4,6ꢀtetraꢀOꢀbenzoyl βꢀDꢀglucopyranoside (10): Eluent
for purification: 20% ethyl acetate in nꢀhexane; crystalline white solid; yield 510 mg
o
25
(92%); mp 213ꢀ216 C; [α]D +8.1 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 1730, 1603, 1450;
1H NMR (399.78 MHz, CDCl3): δ 4.15 (ddd, J = 9.2, 6.0, 2.8 Hz, 1H), 4.45 (dd, J = 12.3,
6.1 Hz, 1H), 4.57 (dd, J = 12.3, 2.8 Hz, 1H), 5.75 – 5.87 (m, 2H), 5.97 (dd, J = 9.6, 8.1
Hz, 1H), 6.05 (t, J = 9.5 Hz, 1H), 7.21 – 7.36 (m, 8H), 7.37 – 7.57 (m, 6H), 7.63 (d, J =
8.3 Hz, 1H), 7.73 (dd, J = 8.2, 1.2 Hz, 2H), 7.83 – 7.94 (m, 5H), 8.06 (dd, J = 8.2, 1.1 Hz,
2H); 13C NMR (100.67 MHz, CDCl3):δ 62.4, 68.9, 69.9, 72.4, 73.1, 106.4, 109.8, 119.7,
124.8, 128.3, 128.4, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5, 128.6, 128.6, 128.9, 129.0,
129.1, 129.1, 129.6, 129.6, 129.8, 129.8, 129.9, 129.9, 130.1, 130.1, 133.2, 133.5, 133.7,
133.7, 143.3, 165.1, 165.2, 165.6, 165.8; HRMS (ESIꢀMS): m/z calcd for
[C40H31N3O10Na+]: 736.1907; Found: 736.1921.
1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2,3,4,6ꢀtetraꢀOꢀbenzoyl αꢀDꢀmannopyranoside (11): Eluent
for purification: 20% ethyl acetate in nꢀhexane; White solid; yield 433 mg (80%); mp 160
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oC; [α]D
+37.7 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 1728, 1601, 1451; H NMR (399.78
5
6
7
8
MHz, CDCl3): δ 4.56 (dd, J = 12.6, 4.2 Hz, 1H), 4.78 (dd, J = 12.5, 2.3 Hz, 1H), 5.35 (ddd,
J = 10.2, 3.9, 2.4 Hz, 1H), 6.01 (d, J = 1.7 Hz, 1H), 6.15 (dd, J = 10.1, 3.3 Hz, 1H), 6.23
(dd, J = 3.4, 1.8 Hz, 1H), 6.33 (t, J = 10.2 Hz, 1H), 7.27 – 7.33 (m, 2H), 7.35 – 7.42 (m,
7H), 7.43 – 7.48 (m, 1H), 7.49 – 7.63 (m, 4H), 7.65 – 7.70 (m, 1H), 7.90 (dd, J = 8.3, 1.1
Hz, 2H), 8.00 – 8.07 (m, 7H); 13C NMR (100.67 MHz, CDCl3): δ 62.2, 65.9, 68.3, 69.5,
71.5,103.2, 108.2, 120.6, 125.0, 127.2, 128.5, 128.5, 128.5, 128.5, 128.6, 128.6, 128.6,
128.6, 128.7, 128.7, 128.8, 128.8, 129.6, 129.8, 129.8, 129.9, 129.9, 129.9, 129.9, 129.9,
129.9, 133.1, 133.5, 133.7, 134.0, 143.5, 165.3, 165.4, 165.5, 166.0; HRMS (ESIꢀMS):
m/z calcd for [C40H31N3O10Na+]: 736.1907; Found: 736.1908.
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1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2,3,4,6ꢀtetraꢀOꢀbenzyl αꢀDꢀmannopyranoside (12): Eluent
for purification: 15% ethyl acetate in nꢀhexane; white solid; yield 415 mg (80%); mp 108
1
oC; [α]D25 ꢀ17.7 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3063, 3031, 2869, 1496, 1453, 1362; H
NMR (399.78 MHz, CDCl3): δ 3.37 (ddd, J = 9.5, 5.1, 1.9 Hz, 1H), 3.56 – 3.66 (m, 2H),
3.73 (dd, J = 11.2, 5.1 Hz, 1H), 4.09 (t, J = 9.3 Hz, 1H), 4.34 (d, J = 11.9 Hz, 1H), 4.42
(d, J = 2.8 Hz, 1H), 4.47 (d, J = 11.9 Hz, 1H), 4.52 – 4.70 (m, 3H), 4.86 – 4.98 (m, 2H),
5.03 (d, J = 12.0 Hz, 1H), 5.41 (s, 1H), 7.14 (dd, J = 6.6, 3.0 Hz, 2H), 7.18 – 7.40 (m,
18H), 7.43 – 7.58 (m, 2H), 7.67 – 7.83 (m, 1H), 7.94 (d, J = 8.3 Hz, 1H);13C NMR (100.67
MHz, CDCl3): δ 69.0, 72.0, 73.4, 73.5, 73.9, 74.6, 75.1, 76.3, 81.4, 107.0, 110.5, 119.6,
124.7, 127.4, 127.5, 127.5, 127.5, 127.7, 127.7, 127.8, 128.0, 128.0, 128.0, 128.0, 128.0,
128.0, 128.2, 128.2, 128.3, 128.3, 128.3, 128.4, 128.4, 128.5, 129.2, 137.7, 138.0, 138.1,
138.1, 143.4; HRMS (ESIꢀMS): m/z calcd for [C40H39N3O6Na+]: 680.2737;
Found:680.2738.
1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2,3,4,6ꢀtetraꢀOꢀbenzoyl βꢀDꢀgalactopyranoside (13): Eluent
for purification: 20% ethyl acetate in nꢀhexane; white solid; yield 505 mg (90%); mp 211
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oC; [α]D +40.4 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 1727, 1451;1H NMR (399.78 MHz,
5
6
C
DCl3): δ 4.32 – 4.39 (m, 1H), 4.46 (dd, J = 11.6, 5.2 Hz, 1H), 4.58 (dd, J = 11.6, 7.5 Hz,
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1H), 5.74 (dd, J = 10.3, 3.4 Hz, 1H), 5.82 (d, J= 8.4 Hz, 1H), 6.02 – 6.07 (m, 1H), 6.20
(dd, J = 10.3, 8.4 Hz, 1H), 7.21 – 7.31 (m, 5H), 7.33 – 7.55 (m, 8H), 7.61 – 7.73 (m, 4H),
7.81 (dd, J = 8.2, 1.2 Hz, 2H), 7.94 (d, J = 8.5 Hz, 1H), 8.04 – 8.16 (m, 4H); 13C NMR
(100.67 MHz, CDCl3): δ 62.0, 67.7, 67.8, 71.6, 72.7, 107.1, 109.9, 119.9, 124.9, 128.4,
128.4, 128.5, 128.5, 128.6, 128.7, 128.8, 128.8, 128.8, 128.9, 129.0, 129.0, 129.1, 129.7,
129.7, 129.7, 129.9, 129.9, 130.1, 130.1, 130.1, 130.1, 133.3, 133.7, 133.8, 134.0, 143.5,
165.5, 165.5, 165.5, 165.9; HRMS (ESIꢀMS): m/z calcd for [C40H31N3O10Na+]: 736.1907;
Found: 736.1915.
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1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2,3,4ꢀtriꢀOꢀbenzoyl αꢀ
Lꢀrhamnopyranoside (14): Eluent for
purification: 20% ethyl acetate in nꢀhexane; white solid; yield 405 mg (90%); mp 112 oC;
25
1
[α]D +17.1 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3067, 2983, 1729, 1353; H NMR (399.78
MHz, CDCl3): δ 1.49 (d, J = 6.2 Hz, 3H), 5.14 (dd, J = 9.9, 6.2 Hz, 1H), 5.88 – 5.99 (m,
2H), 6.12 (dd, J = 10.1, 3.6 Hz, 1H), 6.24 (dd, J = 3.6, 1.7 Hz, 1H), 7.31 (t, J = 7.8 Hz,
2H), 7.40 – 7.66 (m, 9H), 7.72 (d, J = 8.3 Hz, 1H), 7.93 (dd, J = 8.3, 1.2 Hz, 2H), 8.04 –
8.18 (m, 5H);13C NMR (100.67 MHz, CDCl3): δ 17.4, 68.7, 69.5, 69.7, 70.9, 103.5, 108.3,
120.6, 124.9, 127.3, 128.4, 128.4, 128.6, 128.6, 128.6, 128.7, 128.8, 128.8, 128.8, 129.0,
129.8, 129.8, 129.9, 129.9, 130.0, 130.0, 133.4, 133.6, 133.9, 143.5, 165.5, 165.5, 165.7;
HRMS (ESIꢀMS): m/z calcd for [C33H27N3O8Na+]: 616.1696; Found: 616.1694.
1Hꢀbenzo[d][1,2,3]triazolꢀ1ꢀyl 2ꢀdeoxyꢀ2ꢀ(((2,2,2ꢀtrichloroethoxy)carbonyl)amino)ꢀ3,4,6ꢀ
triꢀOꢀacetylꢀβꢀDꢀglucopyranoside (15): Eluent for purification: 35% ethyl acetate in nꢀ
hexane; white solid; yield 408 mg (90%); mp 186 oC; [α]D25 +37.4 (c 1.0, CHCl3); IR(cmꢀ1,
CHCl3): 3268, 3046, 1735, 1353;1H NMR (399.78 MHz, CDCl3): δ 1.88 (s, 3H), 2.03 (s,
3H), 2.08 (s, 3H), 3.81 (ddd, J = 10.0, 5.4, 2.3 Hz, 1H), 4.05 (dd, J = 12.3, 2.3 Hz, 1H),
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4.12 – 4.21 (m, 1H), 4.26 (dd, J = 12.3, 5.4 Hz, 1H), 4.72 (d, J = 12.1 Hz, 1H), 4.86 (t, J =
18.6 Hz, 1H), 5.14 (t, J = 9.7 Hz, 1H), 5.48 – 5.57 (m, 1H), 5.68 (d, J = 8.8 Hz, 1H), 6.54
(d, J = 9.1 Hz, 1H), 7.35 – 7.44 (m, 1H), 7.51 (ddd, J = 10.6, 5.7, 2.2 Hz, 1H), 7.66 (d, J =
8.3 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H);13C NMR (100.67 MHz, CDCl3): δ 20.6, 20.7, 20.7,
54.5, 61.7, 68.5, 71.5, 72.5, 74.7, 95.5, 106.3, 110.3, 119.9, 125.1, 128.6, 129.2, 143.4,
154.8, 169.6, 170.5, 170.7; HRMS (ESIꢀMS): m/z calcd for [C21H23Cl3N4O10Na+]:
619.0377; Found: 619.0371.
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1ꢀdeoxyꢀ1ꢀallyl 2,3,4,6ꢀtetraꢀOꢀbenzyl αꢀDꢀglucopyranoside (16): Eluent for purification:
o
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10% ethyl acetate in nꢀhexane; pale yellow solid; yield 38 mg (90%); mp 59 C; [α]D
1
+55.8(c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3268, 3046, 2912, 1600, 1460, 1353; H NMR
(399.78 MHz, CDCl3): δ 2.37 ꢀ 2.7(m, 2H), 3.57 – 3.84 (m, 6H), 4.14 (dt, J=1.2, 5.1, 1H),
4.42 – 4.51 (m, 2H), 4.59 – 4.54 (m, 2H), 4.66 – 4.73 (m, 1H), 4.81 (dd, J=10.7, 1.6, 2H),
4.94 (d, J=10.9, 1H), 5.10 (dt, J=10.2, 5.2, 2H), 5.82 (ddt, J=17.2, 10.2, 6.8, 1H), 7.12
(dd, J=6.9, 2.5, 2H), 7.21 – 7.4 (m, 18H); 13C NMR (100.67 MHz, CDCl3): δ 68.2, 71.2,
73.2, 73.6, 73.6, 75.2, 76.6, 78.2, 80.2, 80.2, 82.5, 117.0, 127.7, 127.8, 127.9, 127.9,
127.9 (2C), 128.0 (2C), 128.5 (2C), 128.5 (2C), 128.5 (2C), 128.5 (4C), 128.6 (2C),
134.8, 138.1, 138.2, 138.3, 138.3; HRMS(ESIꢀMS): m/z calcd for [C37H40O5Na+]:
587.2773; Found: 587.2776.
1ꢀdeoxyꢀ1ꢀazido
2,3,4,6ꢀtetraꢀOꢀbenzylꢀα/βꢀDꢀglucopyranoside
(17):
Eluent
for
purification: 10% ethyl acetate in nꢀhexane; pale yellow solid; yield 40 mg (93%); mp 55
25
oC; [α]D +22.9 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3268, 3046, 2912, 2170, 1600, 1460,
1
1353; H NMR (399.78 MHz, CDCl3): δ 3.65 (ddd, J = 9.8, 6.4, 4.2 Hz, 6H), 3.79 – 3.69
(m, 2H), 3.87 (t, J = 9.3 Hz, 2H), 4.48 (dd, J = 11.4, 3.8 Hz, 4H), 4.53 – 4.62(m, 2H),
4.65 (dd, J = 15.1, 7.5 Hz, 2H), 4.79 (dd, J = 15.1, 8.3 Hz, 4H), 4.85 (dd,J = 12.4, 7.4
Hz, 4H), 4.93 (t, J = 11.3 Hz, 2H), 5.23 (d, J = 4.1 Hz, 2H), 7.08 – 7.21 (m, 4H), 7.22 ꢀ
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7.44 (m, 36H); 13C NMR (100.67 MHz, CDCl3): δ 68.2, 68.5, 72.6, 73.6, 73.7, 73.9, 75.2,
75.3, 75.9, 76.0, 77.1, 77.2, 77.4, 79.5, 81.8, 81.8, 81.9, 85.0, 88.2, 90.3, 127.8, 127.9,
127.9, 127.9 (3C), 128.1 (4C), 128.1 (5C), 128.2 (2C), 128.3, 128.6 (6C), 128.5 (6C),
128.6 (6C), 128.8 (4C), 137.7, 137.8, 137.8, 137.9, 138.0, 138.1, 138.4, 138.6; HRMS
(ESIꢀMS): m/z calcd for [C34H35O5N3Na+]: 588.2424; Found: 588.2439.
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Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀDꢀglucopyranosyl)ꢀαꢀDꢀ
glucopyranoside (23): Eluent for purification: 20% ethyl acetate in nꢀhexane; fluffy solid;
o
yield 69 mg (93%); mp 58 C; [α]D25 ꢀ 25.2 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 2925, 2856,
1725, 1600; 1H NMR (399.78 MHz, CDCl3): δ 3.27 (s, 3H), 3.38 – 3.55 (m, 3H), 3.73 (ddt,
J = 11.0, 7.8, 3.6 Hz, 2H), 3.89 (t, J = 9.2 Hz, 1H), 3.98 (t, J = 9.4 Hz, 1H), 4.27 (dd, J =
12.1, 5.0 Hz, 1H), 4.35 (d, J = 12.1 Hz, 1H), 4.41 (dd, J = 12.1, 3.4 Hz, 1H), 4.50 – 4.62
(m, 2H), 4.70 – 4.85 (m, 4H), 5.09 (d, J = 11.2 Hz, 1H), 5.48 (dd, J = 9.4, 8.2 Hz, 1H),
5.52 – 5.70 (m, 2H), 7.16 – 7.28 (m, 10H), 7.29 – 7.41 (m, 9H), 7.41 – 7.54 (m, 8H), 7.77
– 7.81 (m, 2H), 7.88 (d, J = 7.5 Hz, 4H), 7.95 – 7.98 (m, 2H); 13C NMR (100.67 MHz,
C
DCl3): δ 55.4, 63.2, 67.6, 69.5, 69.9, 71.9, 72.3, 73.2, 73.6, 73.7, 75.4, 77.3, 78.8, 80.0,
98.5, 100.5, 127.2, 127.5, 127.5, 127.8, 128.1, 128.1, 128.1, 128.1, 128.1, 128.1, 128.1,
128.3, 128.3, 128.3, 128.3, 128.4, 128.4, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5, 128.9,
128.9, 128.9, 129.1, 129.7, 129.7, 129.7, 129.8, 129.8, 129.8, 129.8, 129.8, 133.0, 133.2,
133.4, 133.4, 137.9, 138.4, 139.3, 164.9, 165.1, 165.8, 166.1; HRMS (ESIꢀMS): m/z
calcd for [C62H58O15Na+]: 1065.3673; Found: 1065.3668.
Methyl
2,3,4ꢀtriꢀOꢀbenzoylꢀ6ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoyl
βꢀD
ꢀglucopyranosyl)
αꢀDꢀ
glucopyranoside (24): Eluent for purification: 20% ethyl acetate in nꢀhexane; white solid;
o
25
yield 68 mg (95%); mp 86 C; [α]D +31.3 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 1735, 1452,
1360; 1H NMR (399.78 MHz, CDCl3): δ 3.10 (s, 3H), 3.79 (dd, J = 11.3, 7.6 Hz, 1H), 4.07
– 4.18 (m, 2H), 4.19 – 4.27 (m, 1H), 4.45 (dd, J = 12.2, 5.0 Hz, 1H), 4.61 (dd, J = 12.1,
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3.1 Hz, 1H), 4.90 – 5.02 (m, 2H), 5.10 (dd, J = 10.2, 3.6 Hz, 1H), 5.32 (t, J = 9.9 Hz, 1H),
5.57 (dd, J = 9.7, 7.9 Hz, 1H), 5.66 (t, J = 9.7 Hz, 1H), 5.93 (t, J = 9.7 Hz, 1H), 6.08 (t, J =
9.8 Hz, 1H), 7.25 (td, J = 7.7, 4.2 Hz, 4H), 7.29 – 7.36 (m, 7H), 7.36 – 7.43 (m, 5H), 7.44
– 7.56 (m, 5H), 7.75 – 7.82 (m, 3H), 7.83 – 7.85 (m, 2H), 7.86 – 7.89 (m, 3H), 7.91 – 7.94
(m, 2H), 7.95 – 8.04 (m, 4H); 13C NMR (100.67 MHz, CDCl3): δ 55.1, 63.1, 68.8, 69.0,
69.7, 69.8, 70.4, 72.0, 72.1, 72.4, 72.9, 96.5, 101.9, 128.3, 128.3, 128.3, 128.4, 128.4,
128.4, 128.4, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.8, 128.9, 128.9, 129.1,
129.3, 129.4, 129.6, 129.7, 129.7, 129.7, 129.8, 129.8, 129.8, 129.9, 129.9, 129.9, 129.9,
129.9, 130.0, 130.0, 130.0, 133.1, 133.2, 133.3, 133.3, 133.4, 133.5, 133.5, 165.3, 165.3,
165.5, 165.8, 165.8, 165.9, 166.2; HRMS (ESIꢀMS): m/z calcd for
[C62H52O18Na+]:1107.3051; Found: 1107.3050.
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Methyl
2,3,4ꢀtriꢀOꢀbenzoylꢀ6ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoyl
βꢀD
ꢀglucopyranosyl)
αꢀDꢀ
galactopyranoside (25): Eluent for purification: 20% ethyl acetate in nꢀhexane; white
o
25
solid; yield 68 mg (95%); mp 82 C; [α]D +6.0 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3022,
1727; 1H NMR (399.78 MHz, CDCl3): δ 3.10 (s, 3H), 3.80 (dd, J = 11.3, 7.6 Hz, 1H), 4.18
(dd, J = 11.3, 1.6 Hz, 1H), 4.24 – 4.29 (m, 1H), 4.33 (s, 1H), 4.38 – 4.44 (m, 1H), 4.60
(dd, J = 11.2, 6.4 Hz, 1H), 4.90 – 4.98 (m, 2H), 5.06 (dd, J = 10.2, 3.6 Hz, 1H), 5.34 (t, J
= 9.9 Hz, 1H), 5.64 (dd, J = 10.4, 3.5 Hz, 1H), 5.84 (dd, J = 10.4, 7.9 Hz, 1H), 6.00 (d, J =
3.3 Hz, 1H), 6.08 (t, J = 9.8 Hz, 1H), 7.20 – 7.30 (m, 4H), 7.32 – 7.60 (m, 17H), 7.75 –
7.82 (m, 4H), 7.91 (ddd, J = 18.1, 8.1, 1.0 Hz, 4H), 8.00 (ddd, J = 7.1, 3.4, 2.0 Hz, 4H),
8.04 – 8.08 (m, 2H); 13C NMR (100.67 MHz, CDCl3): δ 55.2, 62.0, 68.2, 68.8, 69.3, 69.7,
69.9, 70.5, 71.5, 71.7, 96.6, 102.4, 128.3, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5,
128.5, 128.6, 128.6, 128.6, 128.6, 128.7, 128.7, 128.9, 128.9, 129.1, 129.2, 129.3, 129.3,
129.5, 129.5, 129.7, 129.7, 129.8, 129.9, 129.9, 129.9, 129.9, 129.9, 130.0, 130.0, 130.0,
130.1, 130.1, 130.1, 133.2, 133.4, 133.4, 133.4, 133.4, 133.6, 133.7, 165.5, 165.6, 165.6,
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165.7, 165.8, 165.8, 166.1;HRMS (ESIꢀMS): m/z calcd for [C62H52O18Na+] :1107.3051;
Found:1107.3051.
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Cholesteryl 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀDꢀglucopyranoside (26): Eluent for purification:
9
20% ethyl acetate in nꢀhexane; white solid; yield 61 mg (90%); mp 202 oC; [α]D25 ꢀ11.3(c
1.0, CHCl3); IR(cmꢀ1, CHCl3): 2928, 2860, 1729; 1H NMR (399.78 MHz, CDCl3): δ 0.64 (s,
3H), 0.84 (d, J = 1.8 Hz, 3H), 0.86 (d, J = 1.7 Hz, 3H), 0.88 (s, 3H), 0.90 (d, J = 6.5 Hz,
3H), 0.95 – 1.24 (m, 9H), 1.27 – 1.71 (m, 14H), 1.86 – 1.95 (m, 2H), 1.95 – 2.03 (m, 1H),
2.04 – 2.22 (m, 2H), 3.52 (dt, J = 10.6, 5.4 Hz, 1H), 4.14 (ddd, J = 9.5, 5.9, 3.4 Hz, 1H),
4.51 (dd, J = 12.0, 5.9 Hz, 1H), 4.59 (dd, J = 12.0, 3.3 Hz, 1H), 4.93 (d, J = 7.9 Hz, 1H),
5.21 (d, J = 5.1 Hz, 1H), 5.49 (dd, J = 9.8, 7.9 Hz, 1H), 5.62 (t, J = 9.7 Hz, 1H), 5.88 (t, J
= 9.6 Hz, 1H), 7.20 – 7.42 (m, 9H), 7.43 – 7.57 (m, 3H), 7.77 – 7.85 (m, 2H), 7.89 (dd, J
= 8.2, 1.2 Hz, 2H), 7.91 – 7.97 (m, 2H), 7.95 – 8.06 (m, 2H); 13C NMR (100.67 MHz,
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C
DCl3): δ 12.0, 18.9, 19.4, 21.1, 22.7, 23.0, 23.9, 24.4, 28.2, 28.4, 29.7, 29.8, 31.9, 32.0,
35.9, 36.3, 36.8, 37.2, 39.0, 39.7, 39.9, 42.4, 50.2, 56.3, 56.9, 63.5, 70.2, 72.2, 72.2,
73.2, 80.6, 100.3, 122.1, 128.4, 128.4, 128.5, 128.5, 128.5, 128.6, 128.6, 128.9, 129.0,
129.6, 129.8, 129.8, 129.9, 129.9, 129.9, 129.9, 130.0, 130.0, 130.0, 133.2, 133.3, 133.3,
133.6, 140.5, 165.2, 165.4, 166.0, 166.2; HRMS (ESIꢀMS): m/z calcd for [C61H72O10Na+]:
987.5023; Found:987.5023.
(1S,2R,5S)ꢀ2ꢀisopropylꢀ5ꢀmethylcyclohexyl 2,3,4,6ꢀtetraꢀOꢀbenzoylꢀβꢀ
Dꢀglucopyranoside
(27): Eluent for purification: 10% ethyl acetate in nꢀhexane; white solid; yield 48 mg
o
25
(95%); mp 63 C; [α]D ꢀ 19.7(c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 2953, 2951, 2866, 1729,
1
1601; H NMR (399.78MHz, CDCl3): δ 0.60 – 0.92 (m, 14H), 1.56 (d, J = 12.3 Hz, 2H),
1.94 (d, J = 12.2 Hz, 1H), 2.12 – 2.33 (m, 1H), 3.48 (d, J = 4.0 Hz, 1H), 4.04 – 4.22 (m,
1H), 4.49 (dd, J = 12.0, 5.7 Hz, 1H), 4.57 – 4.74 (m, 1H), 4.93 (d, J = 8.0 Hz, 1H), 5.50
(dd, J = 9.8, 8.0 Hz, 1H), 5.65 (d, J = 9.7 Hz, 1H), 5.83 – 6.05 (m, 1H), 7.22 – 7.43 (m,
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9H), 7.45 – 7.59 (m, 3H), 7.81 – 7.87 (m, 2H), 7.88 – 7.93 (m, 2H), 7.94 – 8.04 (m,
4H).13C NMR (100.67 MHz, CDCl3): δ 15.7, 20.9, 22.1, 23.1, 25.2, 31.5, 34.2, 40.9, 47.4,
63.6, 70.3, 72.1, 72.2, 73.3, 79.2, 99.1, 128.4, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5,
128.5, 129.0, 129.0, 129.0, 129.0, 129.0, 129.6, 129.6,129.7, 129.7, 129.8, 129.9,
129.9, 133.2, 133.2, 133.3, 133.5, 165.2, 165.4, 166.0, 166.2; HRMS (ESIꢀMS): m/z
calcd for [C44H46O10Na+]: 757.2989; Found: 757.2986.
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Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoyl
βꢀDꢀgalactopyranosyl)ꢀαꢀDꢀ
glucopyranoside (28): Eluent for purification: 20% ethyl acetate in nꢀhexane; white solid;
o
25
yield 67 mg (91%); mp 64 C; [α]D ꢀ 23.9 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3030, 2925,
1724;1H NMR (399.78 MHz, CDCl3): δ 3.30 (d, J = 1.1 Hz, 3H), 3.44 (d, J = 10.7 Hz, 1H),
3.46 – 3.58 (m, 2H), 3.70 (d, J = 9.9 Hz, 1H), 3.86 – 3.97 (m, 2H), 3.99 – 4.08 (m, 1H),
4.19 (ddd, J = 11.2, 7.6, 1.3 Hz, 1H), 4.32 (d, J = 12.2 Hz, 1H), 4.34 – 4.45 (m, 1H), 4.58
(d, J = 3.6 Hz, 1H), 4.59 – 4.68 (m, 1H), 4.71 – 4.83 (m, 3H), 4.91 (d, J = 11.1 Hz, 1H),
5.18 (d, J = 11.1 Hz, 1H), 5.23 – 5.37 (m, 1H), 5.70 (ddd, J = 9.9, 8.0, 1.4 Hz, 1H), 5.85
(d, J = 3.3 Hz, 1H), 7.14 – 7.32 (m, 10H), 7.33 – 7.58 (m, 17H), 7.72 – 7.79 (m, 2H), 7.80
– 7.88 (m, 2H), 7.90 – 7.98 (m, 2H), 7.97 – 8.06 (m, 2H); 13C NMR (100.67 MHz, CDCl3):
δ 55.5, 61.5, 67.7, 68.0, 69.6, 70.4, 71.1, 72.0, 73.7, 73.8, 75.4, 76.8, 78.8, 80.0, 98.7,
100.5, 127.3, 127.3, 127.3, 127.4, 127.9, 127.9, 128.2, 128.2, 128.2, 128.4, 128.4, 128.4,
128.4, 128.5, 128.5, 128.5, 128.5, 128.6, 128.6, 128.7, 128.7, 128.9, 128.9, 128.9, 129.2,
129.3, 129.6, 129.8, 129.8, 129.8, 129.8, 129.9, 129.9, 130.0, 130.0, 133.3, 133.3, 133.4,
133.5, 137.9, 138.5, 139.5, 165.0, 165.6, 165.6, 166.0; HRMS (ESIꢀMS): m/z calcd for
[C62H58O15Na+]:1065.3673; Found: 1065.3670.
Benzyl 2,3,4,6ꢀtetraꢀOꢀbenzoyl βꢀDꢀglucopyranoside (29): Eluent for purification: 15%
ethyl acetate in nꢀhexane; pale brown solid; yield 44 mg (93%); mp 55 oC; [α]D25 ꢀ 27.1 (c
1
1.0, CHCl3); IR(cmꢀ1, CHCl3): 2957, 2927, 1726, 1601; H NMR (399.78MHz, CDCl3): δ
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4.40 – 4.52 (m, 2H), 4.62 – 4.74 (m, 2H), 4.86 (d, J = 11.9 Hz, 1H), 5.18 (d, J = 1.7 Hz,
1H), 5.76 (dd, J = 3.3, 1.8 Hz, 1H), 5.96 (dd, J = 10.1, 3.4 Hz, 1H), 6.12 (t, J = 10.0 Hz,
1H), 7.21 – 7.30 (m, 2H), 7.32 – 7.46 (m, 12H), 7.46 – 7.53 (m, 1H), 7.53 – 7.65 (m, 2H),
7.83 (dd, J = 8.3, 1.1 Hz, 2H), 7.91 – 7.97 (m, 2H), 8.04 (dd, J = 8.3, 1.1 Hz, 2H), 8.11
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(dd, J = 8.2, 1.3 Hz, 2H); 13C NMR (100.67 MHz, CDCl3):
δ 63.0, 67.1, 69.2, 70.1, 70.3,
70.6, 97.1, 128.3, 128.3, 128.4, 128.4, 128.4, 128.6, 128.6, 128.6, 128.6, 128.7, 128.7,
128.8, 128.8, 129.1, 129.2, 129.4, 129.9, 129.9, 129.9, 129.9, 129.9, 130.0, 130.0, 130.0,
130.0, 133.2, 133.3, 133.6, 133.6, 136.5, 165.5, 165.6, 165.6, 166.3; HRMS (ESIꢀMS):
m/z calcd for [C41H34O10Na+]: 709.2050; Found: 709.2050.
Phenyl 2,3,4,6ꢀtetraꢀOꢀbenzoyl βꢀDꢀglucopyranoside (30): Eluent for purification: 10%
o
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ethyl acetate in nꢀhexane; white solid; yield 44 mg (93%); mp 63 C; [α]D +29.7(c 1.0,
CHCl3); IR(cmꢀ1, CHCl3): 1725, 1597; 1H NMR (399.78 MHz, CDCl3): δ 4.38 (ddd, J = 9.7,
6.7, 3.0 Hz, 1H), 4.57 (dd, J = 12.1, 6.7 Hz, 1H), 4.72 (dd, J = 12.1, 3.0 Hz, 1H), 5.44 (d,
J = 7.8 Hz, 1H), 5.75 (t, J = 9.6 Hz, 1H), 5.86 (dd, J= 9.6, 7.8 Hz, 1H), 6.04 (t, J = 9.5 Hz,
1H), 7.00 – 7.11 (m, 3H), 7.16 – 7.24 (m, 2H), 7.33 (t, J = 7.8 Hz, 2H), 7.43 (dt, J = 23.4,
7.7 Hz, 7H), 7.50 – 7.63 (m, 3H), 7.88 – 7.92 (m, 2H), 7.98 (ddd, J = 9.9, 8.3, 1.1 Hz,
4H), 8.07 (dd, J = 8.2, 1.2 Hz, 2H); 13C NMR (100.67 MHz, CDCl3): δ 63.4, 69.8, 71.8,
72.7, 73.0, 99.8, 117.4, 117.4, 123.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.6,
128.6, 128.8, 128.9, 129.2, 129.6, 129.6, 129.7, 129.9, 129.9, 129.9, 129.9, 129.9, 129.9,
130.0, 130.0, 133.3, 133.4, 133.5, 133.7, 157.1, 165.2, 165.4, 165.9, 166.2; HRMS (ESIꢀ
MS): m/z calcd for [C40H32O10Na+]: 695.1893; Found: 695.1889.
Methyl
2,3,4ꢀtriꢀOꢀbenzoylꢀ6ꢀOꢀ(2,3,4ꢀtriꢀOꢀbenzoyl
αꢀLꢀrhamnopyranosyl)ꢀαꢀDꢀ
glucopyranoside (31): Eluent for purification: 20% ethyl acetate in nꢀhexane; white solid;
yield 81 mg (95%); mp 62 oC; [α]D25 +108.2 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3067, 2948,
1728; 1H NMR (399.78MHz, CDCl3): δ 1.28 (s, 3H), 3.59 (s, 3H), 3.84 (dd, J = 11.8, 7.1
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Hz, 1H), 3.94 (dd, J = 11.8, 2.1 Hz, 1H), 4.11 – 4.20 (m, 1H), 4.38 (dd, J = 9.1, 6.4 Hz,
1H), 5.16 (d, J = 1.5 Hz, 1H), 5.27 – 5.32 (m, 2H), 5.52 (t, J = 9.9 Hz, 1H), 5.64 (t, J = 9.9
Hz, 1H), 5.72 (dd, J = 3.4, 1.7 Hz, 1H), 5.79 (dd, J = 10.1, 3.4 Hz, 1H), 6.21 (t, J = 9.6
Hz, 1H), 7.22 – 7.32 (m, 4H), 7.39 (qd, J = 8.8, 7.5, 3.0 Hz, 8H), 7.46 – 7.54 (m, 5H),
7.60 (t, J = 7.4 Hz, 1H), 7.79 – 7.82 (m, 2H), 7.86 – 7.90 (m, 2H), 7.94 – 8.02 (m, 6H),
8.07 – 8.11 (m, 2H);13C NMR (100.67 MHz, CDCl3): δ 18.0, 56.3, 67.3, 67.4, 70.0, 70.2,
70.3, 70.9, 71.1, 72.3, 72.6, 97.3, 98.7, 128.7, 128.7, 128.7, 128.7, 128.9, 128.9, 128.9,
128.9, 128.9, 128.9, 129.0, 129.0, 129.3, 129.6, 129.7, 129.7, 129.8, 129.9, 130.1, 130.1,
130.2, 130.2, 130.2, 130.2, 130.4, 130.4, 130.4, 130.4, 130.4, 130.4, 133.5, 133.5, 133.8,
133.8, 133.9, 133.9, 165.9, 165.9, 165.9, 166.2, 166.3, 166.3; HRMS (ESIꢀMS): m/z
calcd for [C55H48O16Na+]: 987.2840; Found: 987.2840.
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Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzyl
α,βꢀDꢀglucopyranosyl)ꢀαꢀDꢀ
glucopyranoside (32): Eluent for purification: 20% ethyl acetate in nꢀhexane; Syrup; yield
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71 mg (95%); [α]D +39.9 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3030, 2921, 2804, 1732; 1H
NMR (399.78 MHz, CDCl3): δ 3.40 (d, J = 5.2 Hz, 6H), 3.44 (s, 6H), 3.56 – 3.72 (m, 6H),
3.76 (d, J = 10.5 Hz, 2H), 3.89 (td, J = 12.4, 10.6, 6.5 Hz, 4H), 3.96 (d, J = 9.6 Hz, 2H),
4.11 (t, J = 9.1, 9.1 Hz, 2H), 4.31 (d, J = 12.3 Hz, 2H), 4.38 – 4.50 (m, 4H), 4.50 – 4.61
(m, 8H), 4.64 (d, J = 11.1 Hz, 4H), 4.73 (d, J = 12.2 Hz, 2H), 4.78 – 5.03 (m, 10H), 5.01 –
5.78 (m, 4H), 7.11 – 7.49 (m, 70H);13C NMR (100.67 MHz, CDCl3): δ 55.2, 55.4, 67.9,
68.2, 69.1, 69.6, 70.1, 71.0, 72.3, 73.2, 73.3, 73.4, 73.5, 73.5, 73.7, 74.5, 74.9, 75.0,
75.0, 75.0, 75.2, 75.5, 75.6, 75.7, 76.7, 77.4, 77.7, 78.1, 78.9, 79.5, 80.3, 80.5, 82.1,
82.1, 82.9, 84.9, 96.7, 97.8, 98.5, 102.6, 126.8, 126.8, 126.8, 126.9, 126.9, 127.2, 127.2,
127.2, 127.3, 127.3, 127.3, 127.3, 127.3, 127.4, 127.4, 127.5, 127.6, 127.6, 127.7, 127.7,
127.7, 127.7, 127.8, 127.8, 127.8, 127.8, 127.8, 127.8, 127.9, 127.9, 127.9, 127.9, 127.9,
127.9, 127.9, 128.0, 128.1, 128.1, 128.1, 128.2, 128.3 (12C), 128.3, 128.3, 128.4, 128.4,
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128.4, 128.4, 128.4, 128.4, 128.4, 128.4, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.5,
128.5, 137.9, 138.0, 138.1, 138.1, 138.2, 138.2, 138.4, 138.5, 138.6, 138.6, 138.7, 138.8,
139.0, 139.6; HRMS (ESIꢀMS): m/z calcd for [C62H66O11Na+]: 1009.4503; found:
1009.4501.
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Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4ꢀtriꢀOꢀbenzoyl
αꢀLꢀrhamnopyranosyl)ꢀαꢀDꢀ
glucopyranoside (33): Eluent for purification: 20% ethyl acetate in nꢀhexane;white solid;
o
yield 74 mg (94%); mp 58 C; [α]D +41.3 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3067, 2948, 2961,
25
1728; 1H NMR (399.78 MHz,
C
DCl3): δ 0.89 (d, J = 6.0 Hz, 3H), 3.41 (s, 3H), 3.62 – 3.69 (m,
1H), 3.74 (d, J = 11.0 Hz, 1H), 3.87 (dd, J = 20.5, 10.1 Hz, 2H), 3.94 – 4.07 (m, 2H), 4.38 (td, J =
7.7, 6.9, 3.0 Hz, 1H), 4.57 (q, J = 11.9 Hz, 2H), 4.62 – 4.67 (m, 2H), 4.74 – 4.80 (m, 1H), 4.86 (d,
J = 11.1 Hz, 1H), 5.15 – 5.28 (m, 2H), 5.56 – 5.58 (m, 1H), 5.62 (t, J = 10.0, 1.8 Hz, 1H), 5.79 (dt,
J = 10.2, 2.5 Hz, 1H), 7.09 – 7.22 (m, 6H), 7.24 – 7.35 (m, 9H), 7.36 – 7.50 (m, 7H), 7.50 – 7.63
(m, 2H), 7.79 – 7.96 (m, 4H), 8.02 – 8.14 (m, 2H); 13C NMR (100.67 MHz,
CDCl3): δ 17.3, 55.4,
67.1, 68.4, 70.1, 70.2, 71.4, 71.8, 73.4, 73.5, 74.9, 75.6, 79.8, 80.4, 97.1, 98.1, 127.4 – 128.1
(8C), 128.3 – 128.7 (14C), 129.3 – 130.0 (8C), 133.3, 133.4, 133.6, 137.8, 138.0, 138.8, 165.8,
165.9, 165.9; HRMS(ESIꢀMS): m/z calcd for [C55H54O13Na]+: 945.3462; Found: 945.3459.
Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoyl
αꢀDꢀmannopyranosyl)ꢀαꢀDꢀ
glucopyranoside (34): Eluent for purification: 20% ethyl acetate in nꢀhexane; white solid;
yield 69 mg (93%); mp 64 oC; [α]D25 ꢀ23.8 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 2965, 1730; 1H
NMR (399.78 MHz, CDCl3):δ 3.44 (d, J = 0.9 Hz, 3H), 3.54 – 3.61 (m, 1H), 3.78 (d, J =
10.4 Hz, 1H), 3.84 – 4.00 (m, 3H), 4.06 – 4.15 (m, 1H), 4.24 (dd, J = 12.1, 3.3 Hz, 1H),
4.36 (d, J = 10.0 Hz, 1H), 4.47 (d, J = 12.1 Hz, 1H), 4.54 – 4.68 (m, 4H), 4.74 (d, J = 12.1
Hz, 1H), 4.86 (d, J = 11.0 Hz, 1H), 5.07 (d, J = 11.0 Hz, 1H), 5.62 (s, 1H), 5.74 (dd, J =
2.9, 1.5 Hz, 1H), 5.83 – 5.92 (m, 1H), 6.04 (t, J = 10.1 Hz, 1H), 6.93 – 7.06 (m, 3H), 7.10
– 7.17 (m, 1H), 7.17 – 7.46 (m, 21H), 7.48 – 7.61 (m, 3H), 7.76 – 7.83 (m, 2H), 7.89 –
7.97 (m, 4H), 8.03 – 8.21 (m, 1H); 13C NMR (100.67 MHz, CDCl3): δ 55.5, 62.8, 66.8,
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69.3, 69.7, 69.7, 70.0, 70.6, 73.4, 73.6, 75.5, 76.3, 80.3, 81.5, 98.0, 99.0, 127.3, 127.6,
127.6, 127.7, 127.7, 127.7, 128.1, 128.2, 128.2, 128.3, 128.3, 128.3, 128.3, 128.4, 128.5,
128.5, 128.5, 128.5, 128.5, 128.5, 128.5, 128.6, 128.6, 128.6, 129.1, 129.2, 129.5, 129.8,
129.8, 129.8, 129.9, 129.9, 129.9, 129.9, 130.1, 133.1, 133.2, 133.4, 133.5, 138.0, 138.0,
138.3, 165.0, 165.4, 165.6, 166.2; HRMS (ESIꢀMS): m/z calcd for [C62H58O15Na+]:
1065.3673; Found: 1065.3672.
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Methyl
2,3,4ꢀtriꢀOꢀbenzoylꢀ6ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzoyl
αꢀDꢀmannopyranosyl)ꢀαꢀDꢀ
glucopyranoside (35): Eluent for purification: 20% ethyl acetate in nꢀhexane; white solid;
yield 65 mg (91%); mp 92 oC; [α]D25 +8.7(c 1.0, CHCl3); IR(cmꢀ1, CHCl3): 3022, 1727; 1H
NMR (399.78 MHz, CDCl3): δ 3.62 (s, 3H), 3.78 (dd, J = 10.7, 1.9 Hz, 1H), 4.10 (dd, J =
10.8, 6.2 Hz, 1H), 4.30 – 4.46 (m, 2H), 4.54 (ddd, J = 10.0, 4.8, 2.2 Hz, 1H), 4.63 (dd, J =
12.1, 2.2 Hz, 1H), 5.16 (d, J = 1.5 Hz, 1H), 5.26 (dd, J = 10.2, 3.7 Hz, 1H), 5.33 (d, J =
3.7 Hz, 1H), 5.58 (t, J = 9.9 Hz, 1H), 5.77 (dd, J = 3.2, 1.8 Hz, 1H), 5.99 (dd, J = 10.1, 3.3
Hz, 1H), 6.09 (t, J = 10.0 Hz, 1H), 6.21 (t, J = 9.8 Hz, 1H), 7.26 – 7.36 (m, 6H), 7.38 –
7.50 (m, 11H), 7.55 (t, J = 7.3 Hz, 2H), 7.58 – 7.65 (m, 2H), 7.85 – 7.89 (m, 2H), 7.92 –
7.96 (m, 2H), 7.97 – 8.05 (m, 6H), 8.06 – 8.15 (m, 4H);13C NMR (100.67 MHz, CDCl3): δ
55.8, 62.8, 66.6, 67.0, 68.4, 69.1, 69.5, 70.1, 70.5, 70.7, 72.2, 97.1, 97.6, 128.4, 128.4,
128.4,128.4, 128.4, 128.5, 128.6, 128.6, 128.6, 128.6, 128.6, 128.6, 128.7, 128.7, 128.7,
128.9, 129.2, 129.3, 129.3, 129.4, 129.4, 129.9, 129.9, 129.9, 129.9, 129.9, 130.0, 130.0,
130.0, 130.0, 130.0, 130.1, 130.1, 130.1, 130.1, 133.2, 133.2, 133.3, 133.5, 133.6, 133.6,
133.7, 165.5, 165.5, 165.5, 165.7, 165.9, 165.9, 166.2; HRMS (ESIꢀMS):m/z calcd for
[C62H52O18Na+]: 1107.3051; Found: 1107.3049.
Methyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2ꢀdeoxyꢀ2ꢀ(((2,2,2ꢀtrichloroethoxy)carbonyl)amino)ꢀ3,4,6ꢀ
triꢀOꢀacetylꢀβꢀDꢀglucopyranosyl) αꢀDꢀglucopyranoside (36): Eluent for purification: 25%
o
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ethyl acetate in nꢀhexane; white solid; yield 72 mg (90%); mp 78 C; [α]D +41.3(c 1.0,
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CHCl3); IR(cmꢀ1, CHCl3): 3293, 3021, 2932, 1729, 1604; 1H NMR (399.78 MHz, CDCl3): δ
1.90 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 3.32 (s, 3H), 3.45 – 3.61 (m, 3H), 3.66 (dd, J =
10.8, 2.6 Hz, 2H), 3.75 – 3.92 (m, 4H), 4.10 (dd, J = 12.3, 4.2 Hz, 1H), 4.18 (d, J = 8.3
Hz, 1H), 4.31 (d, J = 12.2 Hz, 1H), 4.54 (d, J = 3.3 Hz, 1H), 4.57 (s, 1H), 4.60 (s, 1H),
4.68 (s, 1H), 4.72 – 4.75 (m, 1H), 4.77 (d, J = 4.9 Hz, 1H), 4.83 (s, 1H), 4.86 (d, J = 6.3
Hz, 1H), 4.91 (d, J = 9.6 Hz, 1H), 4.97 (d, J = 11.5 Hz, 1H), 7.18 – 7.35 (m, 11H), 7.39 –
7.44 (m, 2H), 7.46 – 7.50 (m, 2H), 7.53 (d, J = 2.1 Hz, 1H); 13C NMR (100.67 MHz,
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DCl3): δ 20.8, 20.8, 20.8, 55.4, 56.3, 61.9, 67.3, 68.7, 69.2, 71.3, 72.5, 73.6, 73.8, 74.5,
75.3, 77.2, 78.7, 80.3, 95.7, 98.5, 100.8, 127.2, 127.2, 127.9, 128.2, 128.2, 128.3, 128.3,
128.5, 128.5, 128.6, 129.2, 129.2, 129.3, 129.6, 129.6, 137.5, 138.3, 139.7, 154.0, 169.6,
170.5, 170.8; HRMS (ESIꢀMS): m/z calcd for [C43H50Cl3NO15Na]+: 948.2144; Found:
948.2139.
Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2,3,4,6ꢀtetraꢀOꢀbenzyl
αꢀDꢀmannopyranosyl)ꢀαꢀDꢀ
glucopyranoside (37): Eluent for purification: 20% ethyl acetate in nꢀhexane; syrup; yield
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71 mg (92%); [α]D +18.5 (c 1.0, CHCl3); IR(cmꢀ1, CHCl3):3030, 2921, 2864, 1732; H
NMR (399.78 MHz, CDCl3): δ 3.40 (d, J = 5.2 Hz, 3H), 3.44 (s, 3H), 3.56 – 3.72 (m, 3H),
3.76 (d, J = 10.5 Hz, 1H), 3.89 (td, J = 12.4, 10.6, 6.5 Hz, 2H), 3.96 (d, J = 9.6 Hz,1H),
4.11 (t, J = 9.1, 9.1 Hz, 1H), 4.31 (d, J = 12.3 Hz, 1H), 4.38 – 4.50 (m, 2H), 4.50 – 4.61
(m, 4H), 4.64 (d, J = 11.1 Hz, 2H), 4.73 (d, J = 12.2 Hz, 1H), 4.78 – 5.03 (m, 5H), 5.01 –
5.78 (m, 2H), 7.11 – 7.49 (m, 35H); 13C NMR (100.67 MHz, CDCl3): δ 55.3, 69.4, 69.8,
72.1, 72.3, 73.0, 73.2, 73.3, 74.9, 75.0, 75.0, 75.1, 76.3, 77.1, 77.8, 79.8, 80.0, 81.6,
97.7, 100.6, 126.8 (2C), 127.2 (2C), 127.5 (2C), 127.6 (2C), 127.7 (4C), 127.8 (2C),
128.7 (3C), 128.1 (2C), 128.2 (2C), 128.3 (8C), 128.4 (2C), 128.4 (2C), 128.5 (2C),
137.9, 138.4, 138.4, 138.6, 138.6, 138.7, 138.9; HRMS (ESIꢀMS): m/z calcd for
[C62H66O11Na+]: 1009.4503; Found: 1009.4508.
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