Gold(I)-Catalyzed Intermolecular Rearrangement Reaction of Glycosyl Alkynoic β-Ketoesters for the Synthesis of 4- O-Glycosylated 2-Pyrones

Article abstract of DOI:10.1021/acs.joc.9b01582

A new gold(I)-catalyzed rearrangement reaction with glycosyl alkynoic β-ketoesters as substrates is developed. The rearrangement reactions under the catalysis of PPh₃AuOTf proceeded smoothly to afford a range of 4-O-glycosylated 2-pyrones. Base

Full text of DOI:10.1021/acs.joc.9b01582

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Note
Gold(I)-catalyzed Intermolecular Rearrangement Reaction of Glycosyl
Alkynoic #-Ketoesters for the Synthesis of 4-O-Glycosylated 2-Pyrones
Rongkun Liu, Xiaoqian Li, Xiaona Li, Jiazhe Wang, and You Yang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01582 • Publication Date (Web): 30 Sep 2019
Downloaded from pubs.acs.org on October 1, 2019
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Gold(I)-catalyzed Intermolecular Rearrangement Reaction
of Glycosyl Alkynoic -Ketoesters for the Synthesis of 4-O-
Glycosylated 2-Pyrones
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Rongkun Liu, Xiaoqian Li, Xiaona Li, Jiazhe Wang, and You Yang*
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University
of Science and Technology, 130 Meilong Road, Shanghai 200237, China. E-mail:
yangyou@ecust.edu.cn
Abstract: A new gold(I)-catalyzed rearrangement reaction with glycosyl alkynoic -
ketoesters as substrates is developed. The rearrangement reactions under the catalysis of
PPh3AuOTf proceed smoothly to afford a range of 4-O-glycosylated 2-pyrones. Based on the
isolation of the 4-hydroxy-2-pyrone derivative generated from departure of the leaving group
and the competitive reaction, a plausible mechanism of the gold(I)-catalyzed intermolecular
rearrangement reactions is proposed.
The continuous efforts towards the construction of diverse glycosidic bonds in the past few
decades have generated numerous glycosylation methods for the synthesis of oligosaccharides
and glycoconjugates.1,2 Based on the activation of the C≡C triple bond, glycosylation with
alkynyl-containing glycosides as donors was extensively studied, leading to the innovation of
a range of ester- and ether-type donors with a C≡C triple bond as the key component of the
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leaving group.3-5 Due to the mild reaction conditions and the broad substrate applicability,
gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates as donors has emerged
as an efficient glycosylation method for the synthesis of a wide group of glycosides.3 This
type of glycosylation is usually a bimolecular reaction that involves the nucleophilic attack of
an alcohol on the glycosyl oxocarbenium species generated from the activation of the C≡C
triple bond by the π-acidic gold(I) catalyst.3a Nevertheless, to the best of our knowledge, a
gold(I)-catalyzed unimolecular rearrangement reaction for the synthesis of certain types of O-
glycosides based on the reorganization of the glycosyl leaving group has never been reported.
As gold catalysis has proved to be very suitable for the construction of pyrone natural
products through activation of alkynoic -ketoesters under very mild conditions,6 we
envisioned that introduction of alkynoic -ketoesters to the anomeric position of glycosyl
moieties as leaving groups would result in a new type of glycosylation protocol. Here, we
describe the first example of gold(I)-catalyzed unimolecular rearrangement reaction for the
synthesis of 4-O-glycosylated 2-pyrones utilizing glycosyl alkynoic -ketoesters as substrates.
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At the outset, we chose to synthesize D-glucosyl alkynoic -ketoester 3a as a model
compound for testing the glycosylation (Scheme 1). When perbenzoylated D-glucosyl lactol
1a was condensed with the alkynoic -ketoacid that was readily prepared by the TFA-
mediated cleavage of the known tert-butyl ester 2a,7 almost no reaction took place under the
normal ester-forming conditions such as DCC/DMAP or EDCI/DMAP as promoters.
Alternatively, conversion of lactol 1a to the corresponding imidate in the presence of CCl3CN
and DBU followed by TMSOTf (0.3 equiv)-promoted glycosylation of the above imidate with
excess -ketoacid generated from 2a led to the formation of -ketoester 3a in 63% yield over
two steps. Similarly, -ketoesters 3b-3m containing various sugar types and different
substituents attached at the C≡C triple bonds were prepared in 50–89% yield over two steps
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(Scheme 1). By this method, compounds 3a-3j, 3l and 3m were formed as 1,2-trans-
glycosides due to the neighboring group participation effect,8 while compound 3k was
obtained as a mixture of anomers with the -anomer as the major product (/ = ~1:4). In the
mean time, compounds 3a-3m were found to be an equilibrium mixture of keto/enol
tautomers arising from the properties of -ketoesters. Notably, condensation of the more
reactive perbenzylated D-glucosyl lactol 1h with the -ketoacid derived from the known tert-
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butyl ester7 2b under the promotion of DCC and DMAP afforded -ketoester 3n in 64% yield
with the -anomer as the single product, where the -ketoester was also found to be an
equilibrium mixture of keto/enol tautomers (Scheme 1). This result demonstrated that a direct
condensation approach could also be applied to the synthesis of glycosyl -ketoesters.
Scheme 1. Preparation of D-glucosyl alkynoic -ketoesters 3a-3n.
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The glycosylation properties of D-glucosyl alkynoic -ketoester 3a (1.5 equiv) were
first explored with 4-penten-1-ol 4a (1 equiv) as acceptor (Table 1). Unexpectedly,
PPh3AuOTf (0.1 equiv)-catalyzed glycosylation of 3a with primary alcohol 4a in
dichloromethane at room temperature gave orthoester 5 as the major product in 85% yield
(entry 1). It should be noted that the similar orthoester was also found in the gold(I)-catalyzed
glycosylation of peracetylated D-glucosyl ortho-hexynylbenzoate with cholesterol.9
Considering that glycosyl orthoesters could be converted into the desired glycosides with the
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assistance of Lewis acids,10 addition of triflic acid (0.4 equiv) to the above glycosylation
system led to partial conversion of the orthoester to the -glucoside, affording orthoester 5 in
41% yield and -glucoside 6a in 48% yield (entry 2). Similar results were obtained when
Cu(OTf)2 (1.2 equiv) was added to the previous reaction system (entry 3). Interestingly, the
resulting orthoester 5 was completely converted to the desired -glucoside 6a in 74% yield
upon addition of only 0.1 equiv TMSOTf to the above glycosylation (entry 4).11 When
PPh3AuOTf (0.2 equiv) and TMSOTf (0.1 equiv) were employed for the glycosylation, the
yield of -glucoside 6a was improved to 89% (entry 5).
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Table 1. Screening of conditions for glycosylation of alkynoic -ketoester 3a with 4-penten-
1-ol 4a.
PPh3AuOTf
(equiv)
0.1
entry
1
additive (equiv)
/
reaction time
4 h
product (yield, %)a
5 (85)
5 (41)
6a (48)
2
3
0.1
0.1
TfOH (0.4)
4 h
4 h
5 (41)
6a (44)
Cu(OTf)2 (1.2)
TMSOTf (0.1)
TMSOTf (0.1)
4 h
4 h
6a (74)
6a (89)
4
5
0.1
0.2
a Isolated yield.
With the optimal conditions (0.2 equiv PPh3AuOTf, 0.1 equiv TMSOTf) in hand,
glycosylation of alkynoic -ketoester 3a (1.5 equiv) with alcohols 4b-4d (1 equiv) was
investigated (Table 2). Unfortunately, coupling of 3a with cholesterol 4b led to -glucoside
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6b in low yield (47%), while almost no coupled glycosides 6c and 6d were obtained when
furanose derivative 4c or 1-adamantanol 4d was used as acceptor (entries 1-3). Remarkably,
besides the recovery of unreacted -ketoester 3a, an identical rearrangement byproduct in
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these reactions was isolated in 46–54% yields and assigned to be 4-O--D-glucosylated 2-
pyrones 7a by NMR spectra and HRMS, implying that the 4-hydroxy-2-pyrone derivative
derived from the cleavage of the glycosyl leaving group competed with secondary and tertiary
alcohols in the glycosylation reactions. Thus, the yields for the coupled glycosides 6a-6d and
the rearrangement product 7a in the glycosylation reactions were highly dependent on the
reactivity of the alcohols. Inspired by these results, it was envisaged that the unimolecular
gold(I)-catalyzed rearrangement reaction of glycosyl alkynoic -ketoesters could be achieved
for the synthesis of 4-O-glycosylated 2-pyrones.
Table 2. Investigation of glycosylation of alkynoic -ketoester 3a with alcohols 4b-4d.
7a (yield, %)a
-glucosides (yield, %)a
6b (47)
entry
ROH
4b
1
2
46
50
54
6c (trace)
4c
3
6d (/)
4d
a Isolated yield.
As expected, the PPh3AuOTf (0.2 equiv)-catalyzed rearrangement reaction of D-glucosyl
alkynoic -ketoester 3a proceeded smoothly to provide 4-O--D-glucosylated 2-pyrones 7a in
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74% yield (Scheme 2). The scope of the present rearrangement reaction was further expanded
with -ketoesters 3b-3l as substrates. Under the catalysis of PPh3AuOTf, the rearrangement
reactions of perbenzoylated D-glucosyl, D-mannosyl, L-fucosyl, and L-rhamnosyl alkynoic -
ketoesters 3b-3j with different alkyl and phenyl substituents at the C≡C triple bond afforded
exclusively the desired 4-O--D-glucosylated 2-pyrones 7b-7d, 4-O--D-mannosylated 2-
pyrones 7e-7h, 4-O--L-fucosylated 2-pyrone 7i, and 4-O--L-rhamnosylated 2-pyrone 7j in
satisfactory yields (57–83%). With 3,4,6-tri-O-acetyl 2,2,2-trichloroethoxycarbonylamino (N-
Troc)-protected D-galactosaminyl alkynoic -ketoester 3k, 3-O-TBS-protected D-glucosyl
alkynoic -ketoester 3l and perbenzoylated D-ribosyl alkynoic -ketoester 3m as substrates,
the rearrangement reactions produced 4-O--D-galactosaminylated 2-pyrone 7k, 4-O--D-
glucosylated 2-pyrone 7l and 4-O--D-ribosylated 2-pyrone 7m in 71–76% yields.
PPh3AuOTf (0.2 equiv)-catalyzed reaction of the perbenzylated D-glucosyl alkynoic -
ketoesters 3n resulted in the formation a mixture of 4-O-D-glucosylated 2-pyrone 7n in 83%
yield (/ = 2:3). Since the substrate 3n was a single -anomer, the observed -selectivity of
compound 7n indicated that the released 4-hydroxy-2-pyrone intermediate might prefer the
attack on the activated alkyne–gold donor species or the -contact ion pair via the SN2-like
pathway, affording the -linked glucoside as the major product.
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Scheme 2. PPh3AuOTf-catalyzed rearrangement reaction of glycosyl alkynoic -ketoesters
3a-3n.
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To demonstrate the feasibility of the present rearrangement reaction for the synthesis
of glycosylated 2-pyrone natural products as potential antimicrobial agents, 4-O--D-
glucosylated 2-pyrone 8 that was isolated from Inulanthera nuda was selected as an example
(Scheme 3).12 Removal of the benzoyl groups in 7c with sodium methoxide (0.45 equiv) in
methanol and dichloromethane furnished 4-O--D-glucosylated 2-pyrone 8 in an excellent
95% yield without affecting the lactone in the pyrone ring. It is noteworthy that addition of
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stoichiometric amount of sodium methoxide to the above saponification system might lead to
the cleavage of the lactone in the pyrone ring of 8.
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Scheme 3. Synthesis of 4-O--D-glucosylated 2-pyrone 8 from Inulanthera nuda.
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Since the 4-hydroxy-2-pyrone derivative generated from the glycosyl leaving group
was found to compete with alcohol acceptors in the gold(I)-catalyzed glycosylation of
alkynoic -ketoester, glycosylation of 3b with reactive primary alcohol 4a was performed to
isolate the 4-hydroxy-2-pyrone derivative 9 (Scheme 4). PPh3AuOTf (0.2 equiv)-catalyzed
glycosylation of 3b (1.0 equiv) with 4a (1.0 equiv) gave a mixture of orthoester 5a (50%) and
4-O--D-glucosylated 2-pyrone 7b (19%) as well as 4-hydroxy-2-pyrone derivative 9 (71%)
derived from cleavage of the leaving group. This result revealed that the gold(I)-catalyzed
unimolecular rearrangement reaction might proceed via an intermolecular attack of 4-
hydroxy-2-pyrone 9 on the glycosyl oxocarbenium species upon activation of the alkynyl-
containing leaving group.
Scheme 4. Isolation of the 4-hydroxy-2-pyrone derivative 9 derived from the leaving group.
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To further validate this process, a competitive reaction between the rearrangement
reaction of 3k (1 equiv) and the glycosylation of glucosyl ortho-hexynylbenzoate 10 (1.5
equiv) with the released 4-hydroxy-2-pyrone intermediate was carried out under the
promotion of 0.4 equiv PPh3AuOTf (Scheme 5). Indeed, the 4-hydroxy-2-pyrone intermediate
released from the cyclization of the leaving group in 3k reacted with 10 to provide 4-O--D-
glucosylated 2-pyrone 7c in 21% yield besides the formation of the rearrangement product 7k
(73%).
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Scheme 5. Competitive reaction between the rearrangement reaction and the glycosylation.
Based on these findings, a plausible mechanism for the intermolecular gold(I)-
catalyzed rearrangement reactions of glycosyl alkynoic -ketoesters was proposed as shown
in Scheme 6. Thus, activation of the alkyne of the substrate A by a gold(I) catalyst and
subsequent nucleophilic attack of ester carbonyl group on the short-lived alkyne–gold
complex induced the formation of oxocarbenium ion related species B and 2-pyrone-gold(I)
complex C. After this, a proton was released from the coupling of B or the short-lived alkyne–
gold complex with C to protodeaurate of the 2-pyrone-gold(I) related species, providing the
rearrangement product D as well as the active gold(I) complex for another catalytic cycle.
Scheme 6. The proposed mechanism of gold(I)-catalyzed rearrangement reactions of glycosyl
alkynoic -ketoesters.
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In conclusion, we have developed a new gold(I)-catalyzed rearrangement reaction of
glycosyl alkynoic -ketoesters for the synthesis of 4-O-glycosylated 2-pyrones. By employing
PPh3AuOTf as catalyst, the unimolecular rearrangement reactions with various glycosyl
alkynoic -ketoesters as substrates provided a series of 4-O-glycosylated 2-pyrones including
the 4-O--D-glucosylated 2-pyrone from Inulanthera nuda. A plausible mechanism of the
intermolecular rearrangement reactions of glycosyl alkynoic -ketoesters was proposed based
on the isolation of the 4-hydroxy-2-pyrone species derived from the cleavage of the leaving
group and the competitive reaction. The present rearrangement reaction may find further
application in the synthesis of glycosylated 2-pyrone natural products and congeners for
antibacterial studies.
EXPERIMENTAL SECTION
General Information. All reactions were performed with anhydrous solvents in oven-
dried glassware with magnetic stirring under argon unless otherwise stated. The chemicals
were used as supplied except where noted. Analytical thin layer chromatography (TLC) was
conducted on precoated plates of silica gel (0.25-0.3 mm, Shanghai, China). The TLC plates
were visualized by exposure to UV light or by staining with a sulfuric acid-ethanol solution.
Silica gel column chromatography was performed on silica gel AR (100-200 mesh, Shanghai,
China). Optical rotations (OR) were measured with a Rudolph Research Analytical Autopol I
automatic polarimeter. Melting points were measured with an SGW-X4 apparatus. NMR
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spectra were recorded with a Bruker Avance III 400, Bruker Avance III 500, Bruker Avance
III 600 spectrometer. The 1H and 13C NMR spectra were calibrated against the residual proton
and carbon signals of the solvents as internal references (CDCl3: δH = 7.26 ppm and δC = 77.2
ppm; CD3OD: δH = 3.31 ppm and δC = 49.0 ppm ). Multiplicities are quoted as singlet (s),
broad singlet (br s), doublet (d), triplet (t), quartet (q), doublet of doublets (dd), doublet of
doublet of doublets (ddd), doublet of triplets (dt) or multiplet (m). All NMR chemical shifts (δ)
were recorded in ppm and coupling constants (J) were reported in Hz. High-resolution mass
spectra were recorded on ESI-TOF and EI-TOF spectrometers.
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General procedure for the preparation of alkynoic -ketoesters 2a-2d.7 To a solution
of LDA in THF (0.3 M in THF, 50 mL, 15.00 mmol) at –78 ºC was added t-butyl acetate
(1.43 mL, 10.00 mmol). After stirring at –78 ºC for 0.5 h, 2-ynoate derivative (0.83 mL for
ethyl 3-phenylpropiolate, 0.66 mL for ethyl pent-2-ynoate, 0.58 mL for ethyl but-2-ynoate,
0.84 mL for methyl oct-2-ynoate; 5.00 mmol) was added dropwise and the mixture was
stirred at –78 ºC for 2 h before it was carefully poured into saturated aqueous NH4Cl. The
mixture was extracted with ethyl acetate, washed with water and brine, dried over Na2SO4,
and concentrated in vacuo. The residue was purified by silica gel column chromatography to
give 2a-2d.
tert-Butyl 3-oxo-5-phenylpent-4-ynoate 2a (1.10 g, 90%, yellow oil, petroleum
ether/EtOAc: 100/0→200/1): the known compound 2a was prepared according to the
previous report.7
tert-Butyl 3-oxohept-4-ynoate 2b (950 mg, 97%, yellow oil, petroleum ether/EtOAc:
100/0→200/1): the known compound 2b was prepared according to the previous report.7
tert-Butyl 3-oxohex-4-ynoate 2c (878 mg, 96%, yellow oil, petroleum ether/EtOAc:
1
100/0→200/1): H NMR (400 MHz, CDCl3, mixture of keto/enol tautomers) δ 12.03 (s, 0.16
H), 5.18 (s, 0.16 H), 3.45 (s, 1.68 H), 2.03 (s, 2.47 H), 2.01 (s, 0.48 H), 1.47 (m, 9 H); 13C{1H}
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NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ 179.7, 172.4, 165.6, 155.3, 97.9,
92.3, 91.4, 82.3, 81.7, 79.9, 75.0, 52.8, 28.4, 28.1, 4.5, 4.3; HRMS (EI) m/z calcd for
C10H14O3 [M]+ 182.0943, found 182.0942.
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tert-Butyl 3-oxodec-4-ynoate 2d (982 mg, 82%, yellow oil, petroleum ether/EtOAc:
1
100/0→200/1, known compound7): H NMR (400 MHz, CDCl3, mixture of keto/enol
tautomers) δ 12.02 (s, 0.14 H), 5.18 (s, 0.14 H), 3.44 (s, 1.72 H), 2.38–2.32 (m, 2 H), 1.62–
1.53 (m, 2 H), 1.46 (m, 9 H), 1.39–1.28 (m, 4 H), 0.89 (t, J = 7.2 Hz, 3 H); HRMS (EI) m/z
calcd for C14H22O3 [M]+ 238.1569, found 238.1566.
General procedure for the preparation of glycosyl alkynoic -ketoesters 3a-3m. To a
solution of 2a-2d (489 mg for 2a, 392 mg for 2b, 364 mg for 2c, 476 mg for 2d; 2.00 mmol)
in CH2Cl2 (5 mL) at 0 ºC was added trifluoroacetic acid (5.0 mL). After stirring at room
temperature for 0.5 h, the mixture was concentrated in vacuo to give the corresponding -
ketoacid for the next step without further purification. To a solution of lactol 1a-1g (596 mg
for perbenzoylated D-glucosyl lactol 1a, 596 mg for perbenzoylated D-mannosyl lactol 1b,
476 mg for perbenzoylated L-fucosyl lactol 1c, 476 mg for perbenzoylated L-rhamnosyl lactol
1d, 481 mg for 2-N-Troc-protected D-galactosaminyl lactol 1e, 579 mg for 3-O-TBS-
protected D-glucosyl lactol 1f, 462 mg for perbenzoylated D-ribosyl lactol 1g; 1.00 mmol) and
CCl3CN (1.0 mL, 10.00 mmol) in CH2Cl2 (16 mL) at 0 ºC was added catalytic amount of
DBU (30 μL, 0.20 mmol). After stirring at 0 ºC for 2 h, the mixture was concentrated in vacuo
to give the corresponding crude trichloroacetimidate for the next step without further
purification. To a solution of the above trichloroacetimidate, the above -ketoacid, and freshly
activated 4 Å MS (1.0 g) in anhydrous CH2Cl2 (20 mL) at 0 °C was added dropwise a solution
of TMSOTf (54 μL, 0.30 mmol) in anhydrous CH2Cl2 (0.5 mL). The mixture was stirred at
0 °C for 2 h before a small amount of Et3N was added to quench the reaction. After the
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mixture was filtered and concentrated in vacuo, the residue was purified by silica gel column
chromatography to provide glycosyl alkynoic -ketoesters 3a-3m.
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(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((3-oxo-5-phenylpent-4-
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ynoyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 3a (483 mg, 63% over two steps,
pale yellow solid, toluene/EtOAc: 10/1): mp = 67–69 ºC ; [α]2D0 = –1.8 (c 0.47, CHCl3); H
1
NMR (400 MHz, CDCl3, mixture of keto/enol tautomers) δ 11.43 (s, 0.45 H), 8.06–7.82 (m, 8
H), 7.58–7.28 (m, 17 H), 6.19–6.16 (m, 1 H, H-1), 5.99–5.94 (m, 1 H), 5.79–5.68 (m, 2 H),
5.50 (s, 0.45 H), 4.68–4.60 (m, 1 H), 4.53–4.45 (m, 1 H), 4.38–4.31 (m, 1 H), 3.73 (s, 1.10 H);
13C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ 177.1, 170.2, 166.3,
166.2, 165.8, 165.3, 165.2, 165.1, 164.6, 157.5, 133.7, 133.6, 133.5, 133.4, 133.3, 132.5,
131.4, 130.4, 130.1, 130.0, 129.9, 129.7, 129.6, 128.9, 128.8, 128.7, 128.6, 128.5, 120.6,
119.4, 96.3, 95.1, 93.8, 93.0, 92.3, 87.2, 83.3, 73.5, 73.4, 73.0, 72.9, 70.9, 70.8, 69.2, 69.1,
62.8, 62.7, 50.8; HRMS (ESI) m/z calcd for C45H34O12Na [M + Na]+ 789.1948, found
789.1949.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((3-oxohept-4-ynoyl)oxy)tetrahydro-
2H-pyran-3,4,5-triyl tribenzoate 3b (640 mg, 89% over two steps, pale yellow solid,
toluene/EtOAc: 10/1): mp = 56–58 ºC ; [α]2D0 = +20.5 (c 0.37, CHCl3); H NMR (400 MHz,
1
CDCl3, mixture of keto/enol tautomers) δ 11.38 (s, 0.45 H), 8.05–7.82 (m, 8 H), 7.58–7.28 (m,
12 H), 6.16–6.13 (m, 1 H, H-1), 5.98–5.93 (m, 1 H), 5.78–5.65 (m, 2 H), 5.33 (s, 0.45 H),
4.66–4.62 (m, 1 H), 4.50–4.46 (m, 1 H), 4.35–4.30 (m, 1 H), 3.59 (s, 1.10 H), 2.39–2.33 (q, J
= 7.6 Hz, 0.90 H), 2.23–2.17 (q, J = 7.6 Hz, 1.10 H), 1.19–1.06 (m, 3 H); 13C{1H} NMR (150
MHz, CDCl3, mixture of keto/enol tautomers) δ 177.3, 170.4, 166.3, 165.8, 165.3, 165.2,
165.1, 164.6, 158.0, 133.7, 133.6, 133.5, 133.4, 133.3, 130.1, 130.0, 129.9, 129.7, 129.6,
129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 99.2, 98.8, 95.4, 92.9, 92.2, 79.6, 74.8, 73.5, 73.4,
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73.0, 72.9, 70.9, 70.8, 69.2, 69.0, 62.8, 62.7, 50.9, 13.2, 13.0, 12.8, 12.6; HRMS (ESI) m/z
calcd for C41H34O12Na [M + Na]+ 741.1948, found 741.1949.
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(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((3-oxohex-4-ynoyl)oxy)tetrahydro-
2H-pyran-3,4,5-triyl tribenzoate 3c (524 mg, 74% over two steps, pale yellow solid,
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toluene/EtOAc: 10/1): mp = 53–55 ºC ; [α]2D0 = +23.2 (c 0.33, CHCl3); H NMR (400 MHz,
1
CDCl3, mixture of keto/enol tautomers) δ 11.37 (s, 0.40 H), 8.05–7.82 (m, 8 H), 7.58–7.27 (m,
12 H), 6.16–6.13 (m, 1 H, H-1), 5.98–5.93 (m, 1 H), 5.77–5.65 (m, 2 H), 5.31 (s, 0.40 H),
4.66–4.62 (m, 1 H), 4.51–4.46 (m, 1 H), 4.33 (m, 1 H), 3.58 (s, 1.20 H), 2.00 (s, 1.20 H), 1.83
(s, 1.80 H); 13C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ 177.3, 170.4,
166.3, 165.8, 165.3, 165.2, 165.1, 164.6, 157.9, 133.8, 133.7, 133.6, 133.5, 133.4, 133.3,
130.0, 129.9, 129.7, 129.6, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 95.4, 93.8, 93.6, 92.9,
92.2, 79.5, 74.7, 73.5, 73.4, 73.0, 72.9, 70.9, 70.8, 69.2, 69.0, 62.8, 62.7, 50.9, 4.6, 4.1;
HRMS (ESI) m/z calcd for C40H32O12Na [M + Na]+ 727.1791, found 727.1792.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((3-oxodec-4-ynoyl)oxy)tetrahydro-2H-
pyran-3,4,5-triyl tribenzoate 3d (473 mg, 62% over two steps, pale yellow solid,
toluene/EtOAc: 10/1): mp = 57–59 ºC ; [α]2D0 = +9.4 (c 0.57, CHCl3); H NMR (400 MHz,
1
CDCl3, mixture of keto/enol tautomers) δ 11.38 (s, 0.30 H), 8.05–7.81 (m, 8 H), 7.58–7.27 (m,
12 H), 6.15–6.12 (m, 1 H, H-1), 6.04–5.93 (m, 1 H), 5.79–5.65 (m, 2 H), 5.32 (s, 0.30 H),
4.66–4.62 (m, 1 H), 4.50–4.44 (m, 1 H), 4.37–4.31 (m, 1 H), 3.59 (s, 1.00 H), 2.34 (t, J = 7.2
Hz, 0.60 H), 2.18 (t, J = 7.2 Hz, 0.80 H), 1.99 (t, J = 7.2 Hz, 0.60 H), 1.34–1.20 (m, 6 H),
0.60 H), 0.90–0.85 (m, 3 H); 13C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol
tautomers) δ 177.3, 174.5, 170.4, 166.3, 166.2, 165.9, 165.8, 165.6, 165.3, 165.2, 165.1, 165.0,
164.6, 160.0, 158.0, 133.7, 133.6, 133.5, 133.4, 133.3, 130.0, 129.9, 129.7, 129.6, 129.2,
129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 125.5, 103.4, 98.2, 98.1, 97.9, 95.4, 93.4, 92.9,
92.3, 92.2, 80.2, 79.8, 75.5, 73.5, 73.4, 73.3, 73.0, 72.9, 70.9, 70.8, 70.7, 69.2, 69.1, 69.0, 62.9,
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62.8, 50.9, 31.1, 31.0, 27.6, 27.4, 27.3, 22.3, 22.2, 19.4, 19.0, 14.1, 14.0; HRMS (ESI) m/z
calcd for C44H40O12Na [M + Na]+ 783.2417, found 783.2419.
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(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((3-oxo-5-phenylpent-4-
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ynoyl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 3e (429 mg, 56% over two steps,
pale yellow solid, toluene/EtOAc: 10/1): mp = 74–76 ºC ; [α]2D0 = –14.8 (c 0.87, CHCl3); H
1
NMR (400 MHz, CDCl3, mixture of keto/enol tautomers) δ 11.60 (s, 0.35 H), 8.12–7.82 (m, 8
H), 7.66–7.27 (m, 12 H), 6.50–6.46 (m, 1 H, H-1), 6.26–6.19 (m, 1 H), 5.97–5.88 (m, 1 H),
5.79 (m, 1 H), 5.72 (s, 0.35 H), 4.71–4.42 (m, 3 H), 4.02–3.89 (m, 1.30 H); 13C{1H} (150
MHz, CDCl3, mixture of keto/enol tautomers) δ 177.9, 169.7, 166.2, 165.7, 165.4, 165.3,
165.2, 163.7, 158.0, 133.9, 133.7, 133.6, 133.5, 133.3, 133.2, 132.6, 131.8, 131.6, 130.5,
130.1, 130.0, 129.9, 129.8, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 18.4, 128.3, 120.6,
119.2, 96.1, 95.2, 94.3, 91.8, 91.1, 87.3, 83.4, 71.4, 71.3, 69.9, 69.8, 69.5, 69.2, 66.3, 66.1,
62.5, 62.4, 51.3; HRMS (ESI) m/z calcd for C45H34O12Na [M + Na]+ 789.1948, found
789.1951.
(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((3-oxohept-4-ynoyl)oxy)tetrahydro-
2H-pyran-3,4,5-triyl tribenzoate 3f (500 mg, 70% over two steps, pale yellow solid,
toluene/EtOAc: 10/1): mp = 59–63 ºC ; [α]2D0 = –23.3 (c 0.39, CHCl3); H NMR (400 MHz,
1
CDCl3, mixture of keto/enol tautomers) δ 11.56 (s, 0.30 H), 8.12–7.83 (m, 8 H), 7.63–7.28 (m,
12 H), 6.46–6.42 (m, 1 H, H-1), 6.24–6.18 (m, 1 H), 5.94–5.86 (m, 1 H), 5.76 (m, 1 H), 5.54
(s, 0.30 H), 4.72–4.66 (m, 1 H), 4.61–4.46 (m, 2 H), 3.88–3.75 (m, 1.40 H), 2.50–2.42 (m, 2
13
H), 1.28–1.23 (m, 3 H); C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ
178.2, 169.8, 166.3, 165.7, 165.4, 165.3, 165.2, 163.8, 158.4, 133.9, 133.7, 133.6, 133.3,
133.2, 130.1, 130.0, 129.9, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 99.4, 99.3, 95.2,
91.7, 91.0, 79.8, 74.9, 71.3, 71.2, 69.9, 69.8, 69.5, 69.2, 66.3, 66.1, 62.5, 62.4, 51.3, 13.2, 13.0,
12.7; HRMS (ESI) m/z calcd for C41H34O12Na [M + Na]+ 741.1948, found 741.1943.
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(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((3-oxohex-4-ynoyl)oxy)tetrahydro-
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2H-pyran-3,4,5-triyl tribenzoate 3g (456 mg, 65% over two steps, pale yellow solid,
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toluene/EtOAc: 10/1): mp = 62–65 ºC ; [α]2D0 = –24.9 (c 1.0, CHCl3); H NMR (400 MHz,
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CDCl3, mixture of keto/enol tautomers) δ 11.57 (s, 0.30 H), 8.13–7.83 (m, 8 H), 7.63–7.28 (m,
12 H), 6.46–6.43 (m, 1 H, H-1), 6.25–6.18 (m, 1 H), 5.95–5.86 (m, 1 H), 5.77 (m, 1 H), 5.52
(s, 0.30 H), 4.73–4.67 (m, 1 H), 4.60–4.47 (m, 2 H), 3.86–3.74 (m, 1.40 H), 2.12–2.09 (m, 3
13
H); C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ 178.1, 169.8, 166.2,
165.7, 165.4, 165.3, 163.8, 158.4, 133.9, 133.7, 133.5, 133.3, 133.2, 130.1, 130.0, 129.9,
129.1, 129.0, 128.9, 128.8, 128.6, 128.5, 95.1, 94.3, 94.0, 91.7, 91.0, 79.7, 74.8, 71.3, 71.2,
69.9, 69.8, 69.4, 69.2, 66.3, 66.1, 62.5, 62.4, 51.2, 4.6, 4.5; HRMS (ESI) m/z calcd for
C40H32O12Na [M + Na]+ 727.1791, found 727.1790.
(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((3-oxodec-4-ynoyl)oxy)tetrahydro-2H-
pyran-3,4,5-triyl tribenzoate 3h (616 mg, 81% over two steps, pale yellow solid,
toluene/EtOAc: 10/1): mp = 68–70 ºC ; [α]2D0 = –7.3 (c 0.57, CHCl3); H NMR (400 MHz,
1
CDCl3, mixture of keto/enol tautomers) δ 11.56 (s, 0.30 H), 8.12–7.83 (m, 8 H), 7.65–7.28 (m,
12 H), 6.48–6.42 (m, 1 H, H-1), 6.33–6.14 (m, 1 H), 5.94–5.75 (m, 2 H), 5.53 (s, 0.30 H),
4.74–4.57 (m, 2 H), 4.51–4.45 (m, 1 H), 3.88–3.75 (m, 1.40 H), 2.47–2.41 (m, 2 H), 1.67–
13
1.60 (m, 2 H), 1.44–1.26 (m, 4 H), 0.96–0.80 (m, 3 H); C{1H} NMR (150 MHz, CDCl3,
mixture of keto/enol tautomers) δ 178.2, 169.8, 166.3, 165.7, 165.6, 165.5, 165.4, 165.3,
165.2, 164.8, 163.8, 160.2, 158.5, 133.9, 133.8, 133.7, 133.6, 133.5, 133.3, 133.2, 130.1,
130.0, 129.9, 129.2, 129.1, 129.0, 128.8, 128.7, 128.6, 128.5, 98.6, 98.4, 95.2, 92.3, 91.7, 90.9,
80.4, 75.6, 71.6, 71.3, 71.2, 69.9, 69.8, 69.5, 69.2, 69.1, 66.3, 66.2, 66.1, 62.7, 62.5, 62.4, 51.4,
31.2, 31.1, 27.7, 27.6, 27.4, 22.3, 22.2, 19.5, 19.3, 19.2, 14.1, 14.0; HRMS (ESI) m/z calcd for
C44H40O12Na [M + Na]+ 783.2417, found 783.2435.
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(2R,3R,4S,5R,6R)-2-Methyl-6-((3-oxohex-4-ynoyl)oxy)tetrahydro-2H-pyran-3,4,5-
triyl tribenzoate 3i (310 mg, 53% over two steps, pale yellow solid, toluene/EtOAc: 10/1):
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mp = 45–47 ºC ; [α]2D0 = –158.6 (c 0.73, CHCl3); H NMR (400 MHz, CDCl3, mixture of
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keto/enol tautomers) δ 11.43 (s, 0.35 H), 8.10 (m, 2 H), 7.93 (m, 2 H), 7.78 (m, 2 H), 7.63 (m,
1 H), 7.52–7.23 (m, 8 H), 6.10–6.07 (m, 1 H, H-1), 5.92–5.85 (m, 1 H), 5.76 (m, 1 H), 5.63–
5.59 (m, 1 H), 5.35 (s, 0.35 H), 4.27–4.23 (m, 1 H), 3.61 (s, 1.30 H), 2.01 (s, 1.10 H), 1.85 (s,
1.90 H), 1.37–1.36 (m, 3 H); 13C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol
tautomers) δ 177.4, 170.6, 166.0, 165.8, 165.7, 165.4, 165.3, 164.8, 164.6, 157.7, 133.7, 133.6,
133.5, 133.4, 130.2, 130.1, 130.0, 129.9, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.7,
128.6, 128.5, 128.4, 95.5, 95.3, 93.6, 93.5, 93.2, 92.5, 91.4, 90.5, 79.6, 74.7, 72.2, 72.1, 71.5,
71.3, 71.2, 70.9, 70.8, 68.8, 68.7, 68.6, 68.2, 68.1, 67.6, 67.5, 51.3, 51.0, 16.4, 4.5, 4.2;
HRMS (ESI) m/z calcd for C33H28O10Na [M + Na]+ 607.1580, found 607.1576.
(2R,3S,4S,5S,6S)-2-Methyl-6-((3-oxohex-4-ynoyl)oxy)tetrahydro-2H-pyran-3,4,5-
triyl tribenzoate 3j (374 mg, 64% over two steps, pale yellow solid, toluene/EtOAc: 10/1):
mp = 54–57 ºC ; [α]2D0 = +67.5 (c 0.59, CHCl3); H NMR (400 MHz, CDCl3, mixture of
1
keto/enol tautomers) δ 11.60 (s, 0.30 H), 8.11–7.29 (m, 15 H), 6.37–6.34 (m, 1 H, H-1), 5.85–
5.69 (m, 3 H), 5.49 (s, 0.30 H), 4.35–4.22 (m, 1 H), 3.82–3.71 (m, 1.40 H), 2.13–2.09 (m, 3
13
H), 1.40–1.38 (m, 3 H); C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ
178.2, 170.1, 165.8, 165.7, 165.5, 164.0, 158.1, 133.9, 133.7, 133.5, 130.2, 130.0, 129.9,
129.3, 129.2, 129.1, 129.0, 128.8, 128.7, 128.5, 95.3, 94.1, 93.7, 91.8, 91.0, 79.8, 71.3, 71.2,
69.8, 69.7, 69.5, 69.4, 51.3, 17.9, 17.8, 4.6, 4.5; HRMS (ESI) m/z calcd for C33H28O10Na [M +
Na]+ 607.1580, found 607.1579.
(2R,3R,4R,5R)-2-(Acetoxymethyl)-6-((3-oxohex-4-ynoyl)oxy)-5-(((2,2,2-
trichloroethoxy)carbonyl)amino)tetrahydro-2H-pyran-3,4-diyl diacetate 3k (371 mg,
63% over two steps, pale yellow solid, toluene/EtOAc: 10/1): mp = 52–55 ºC ; [α]2D0 = +33.8 (c
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0.40, CHCl3); 1H NMR (400 MHz, CDCl3, mixture of keto/enol tautomers) δ 11.55–11.35 (s,
0.30 H), 6.37–6.23 (m, 0.30 H), 5.95–5.65 (m, 1 H), 5.45–5.07 (m, 3 H), 4.85–4.60 (m, 2 H),
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4.50–4.04 (m, 4 H), 3.73–3.59 (m, 1.40 H), 2.17–1.99 (m, 12 H); C{1H} NMR (150 MHz,
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CDCl3, mixture of keto/enol tautomers) δ 178.9, 177.8, 170.8, 170.7, 170.6, 170.5, 170.4,
170.3, 164.7, 164.0, 158.4, 157.9, 154.7, 154.5, 154.4, 100.8, 97.0, 95.6, 95.5, 95.3, 94.9, 94.7,
93.9, 93.8, 93.4, 92.6, 92.5, 79.7, 75.1, 74.8, 74.7, 74.6, 72.1, 72.0, 70.5, 70.3, 70.0, 69.9, 69.4,
69.0, 68.2, 66.9, 66.6, 66.5, 65.4, 61.6, 61.4, 61.3, 53.5, 51.9, 51.8, 51.4, 51.3, 50.9, 49.2, 49.1,
20.8, 20.7, 4.6, 4.4; HRMS (ESI) m/z calcd for C21H24O12Cl3NNa [M + Na]+ 610.0262, found
610.0252.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-4-((tert-butyldimethylsilyl)oxy)-6-((3-
oxohept-4-ynoyl)oxy)tetrahydro-2H-pyran-3,5-diyl dibenzoate 3l (352 mg, 50% over two
steps, pale red syrup, petroleum ether/EtOAc: 8/1): [α]2D0 = +19.4 (c 1.0, CHCl3); H NMR
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(400 MHz, CDCl3, mixture of keto/enol tautomers) δ 11.42 (s, 0.30 H), 8.05–7.19 (m, 15 H),
5.85–5.82 (m, 1 H, H-1), 5.39–5.28 (m, 1 H), 5.25 (s, 0.30 H), 4.82 (d-like, J = 11.6 Hz, 1 H),
4.60 (d-like, J = 12.0 Hz, 2 H), 4.54–4.49 (m, 1 H), 4.02–3.95 (m, 1 H), 3.76–3.66 (m, 4 H),
3.55–3.46 (m, 1.40 H), 2.37–2.19 (m, 2 H), 1.18–1.08 (m, 3 H), 0.78–0.77 (m, 9 H), 0.00–-
13
0.01 (m, 3 H), -0.16–-0.17 (m, 3 H); C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol
tautomers) δ 178.2, 177.7, 175.2, 170.8, 168.1, 165.4, 165.3, 165.0, 164.4, 157.4, 138.2, 138.1,
138.0, 137.9, 133.4, 133.3, 130.2, 130.0, 129.9, 129.8, 128.6, 128.5, 128.4, 128.1, 128.0,
127.9, 127.8, 127.7, 127.6, 127.5, 98.7, 98.5, 95.8, 93.1, 92.4, 91.5, 79.7, 78.4, 78.3, 78.2,
76.2, 76.1, 75.3, 75.2, 75.0, 74.8, 73.7, 73.4, 73.3, 68.5, 68.4, 68.3, 51.5, 50.9, 25.8, 17.9, 13.1,
13.0, 12.8, 12.6, -4.0, -4.2; HRMS (ESI) m/z calcd for C40H48O9SiNa [M + Na]+ 723.2965,
found 723.2964.
(2R,3R,4R,5S)-2-((benzoyloxy)methyl)-5-((3-oxopentanoyl)oxy)tetrahydrofuran-
3,4-diyl dibenzoate 3m (360 mg, 62% over two steps, pale yellow syrup, petroleum
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ether/EtOAc: 6/1): [α]2D0 = +2.7 (c 0.32, CHCl3); H NMR (400 MHz, CDCl3, mixture of
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keto/enol tautomers) δ 11.53 (s, 0.40 H), 8.07–7.31 (m, 15 H), 6.49 (s, 1 H, H-1), 5.94–5.86
(m, 1 H), 5.82–5.80 (m, 1 H), 5.14 (s, 0.40 H), 4.83–4.72 (m, 2 H), 4.58–4.50 (m, 1 H), 3.48
(s, 1.20 H), 2.45–2.39 (m, 2 H), 1.26–1.20 (m, 3 H); 13C{1H} NMR (150 MHz, CDCl3,
mixture of keto/enol tautomers) δ 177.9, 170.5, 166.2, 166.1, 165.5, 165.4, 165.2, 165.1,
164.7, 157.8, 133.9, 133.8, 133.5, 133.4, 130.1, 130.0, 129.9, 129.7, 129.0, 128.9, 128.8,
128.7, 128.6, 128.5, 128.4, 99.5, 99.0, 98.8, 98.6, 95.5, 80.5, 80.3, 79.7, 75.1, 75.0, 71.6, 71.3,
64.1, 63.6, 51.0, 13.2, 13.1, 13.0, 12.7; HRMS (ESI) m/z calcd for C33H28O10Na [M + Na]+
607.1580, found 607.1581.
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(2R,3R,4S,5R,6R)-3,4,5-Tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-
pyran-2-yl 3-oxohept-4-ynoate 3n. To a solution of lactol 1h (216 mg, 0.40 mmol) and the
corresponding -ketoacid generated from the TFA-mediated cleavage of from 2b (196 mg,
1.00 mmol) in anhydrous CH2Cl2 (10 mL) at 0 ºC was added DCC (206 mg, 1.00 mmol) and
DMAP (15 mg, 0.12 mmol). After stirring at 0 ºC for 1 h, the mixture was filtered and
concentrated in vacuo. The residue was purified by silica gel column chromatography
(toluene/EtOAc: 10/1) to provide D-glucosyl alkynoic -ketoesters 3n (170 mg, 64%) as a
pale yellow syrup: [α]2D0 = +68.3 (c 0.31, CHCl3); H NMR (400 MHz, CDCl3, mixture of
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keto/enol tautomers) δ 11.73 (s, 0.20 H), 7.34–7.26 (m, 18 H), 7.14–7.12 (m, 2 H), 6.38 (d, J
= 3.6 Hz, 0.80 H), 5.35 (s, 0.20 H), 4.97–4.90 (m, 1 H), 4.87–4.77 (m, 2 H), 4.74–4.58 (m,
3.20 H), 4.54–4.45 (m, 2 H), 3.98–3.61 (m, 7.60 H), 2.43–2.28 (m, 2 H), 1.23–1.12 (m, 3 H);
13C{1H} NMR (150 MHz, CDCl3, mixture of keto/enol tautomers) δ 178.4, 171.0, 164.9,
157.3, 138.8, 138.2, 138.0, 137.7, 128.8, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0,
127.9, 127.8, 98.4, 96.1, 91.4, 90.4, 81.8, 81.7, 80.0, 79.0, 78.9, 75.9, 75.8, 75.4, 73.7, 73.4,
73.2, 73.1, 68.2, 68.1, 51.4, 13.2, 13.1, 12.9, 12.7; HRMS (ESI) m/z calcd for C41H42O8Na[M
+ Na]+ 685.2777, found 685.2766.
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(3aR,5R,6R,7S,7aR)-5-((Benzoyloxy)methyl)-2-(pent-4-en-1-yloxy)-2-
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phenyltetrahydro-5H-[1,3]dioxolo[4,5-b]pyran-6,7-diyl dibenzoate 5.13 To a solution of 3a
(46 mg, 0.06 mmol), 4-penten-1-ol 4a (4.1 μL, 0.04 mmol) and freshly activated 4 Å MS (50
mg) in anhydrous CH2Cl2 (1 mL) at room temperature was added the freshly prepared
solution of PPh3AuOTf in anhydrous CH2Cl2 (0.02 M, 0.20 mL) under argon. After stirring
for 4 h at room temperature, the mixture was filtered and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/EtOAc: 10/1) to give the
known compound 5 (23 mg, 85%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.10–7.77
(m, 8 H), 7.61–7.24 (m, 12 H), 6.05 (d, J = 5.2 Hz, 1 H), 5.78–5.70 (m, 2 H), 5.50 (d-like, J =
8.8 Hz, 1 H), 4.98–4.90 (m, 2 H), 4.79–4.76 (m, 1 H), 4.52 (dd, J = 2.8, 12.0 Hz, 1 H), 4.37
(dd, J = 4.8, 12.0 Hz, 1 H), 4.16–4.12 (m, 1 H), 3.39–3.26 (m, 2 H), 2.05 (m, 2 H), 1.62 (m, 2
H).
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(2R,3R,4S,5R,6R)-2-((Benzoyloxy)methyl)-6-(pent-4-en-1-yloxy)tetrahydro-2H-
pyran-3,4,5-triyl tribenzoate 6a.8 To a solution of 3a (46 mg, 0.06 mmol), 4-penten-1-ol 4a
(4.1 μL, 0.04 mmol) and freshly activated 4 Å MS (50 mg) in anhydrous CH2Cl2 (1 mL) at
room temperature was added was added the freshly prepared solution of PPh3AuOTf in dry
CH2Cl2 (0.02 M, 0.40 mL) under argon. After stirring at room temperature for 2 h, a solution
of TMSOTf in CH2Cl2 (0.04 M, 0.10 mL) was added. The mixture was stirred for 2 h before a
small amount of Et3N was added to quench the reaction. The mixture was filtered and
concentrated in vacuo. The residue was purified by silica gel column chromatography
(petroleum ether/EtOAc: 10/1) to give the known compound 6a (24 mg, 89%) as a white solid:
1H NMR (400 MHz, CDCl3) δ 8.03–7.82 (m, 8 H), 7.56–7.26 (m, 12 H), 5.91 (t, J = 9.6 Hz, 1
H), 5.70–5.59 (m, 2 H), 5.53 (dd, J = 7.6, 9.6 Hz, 1 H), 4.86–4.80 (m, 3 H), 4.64 (dd, J = 3.2,
12.0 Hz, 1 H), 4.50 (dd, J = 5.2, 12.0 Hz, 1 H), 4.18–4.13 (m, 1 H), 3.95–3.90 (m, 1 H), 3.58–
3.53 (m, 1 H), 2.01–1.93 (m, 2 H), 1.70–1.62 (m, 2 H).
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General procedure for PPh3AuOTf-catalyzed rearrangement reaction of glycosyl
alkynoic -ketoesters 3a-3n. To a solution of 3a-3n (77 mg for 3a, 72 mg for 3b, 70 mg for
3c, 76 mg for 3d, 77 mg for 3e, 72 mg for 3f, 70 mg for 3g, 76 mg for 3h, 58 mg for 3i, 58
mg for 3j, 59 mg for 3k, 70 mg for 3l, 58 mg for 3m, 66 mg for 3n; 0.10 mmol) and freshly
activated 4 Å MS (100 mg) in anhydrous CH2Cl2 (1 mL) at room temperature was added the
freshly prepared solution of PPh3AuOTf in dry CH2Cl2 (0.02 M, 1.0 mL) under argon. After
stirring at room temperature for 2 h, the mixture was filtered and concentrated in vacuo. The
residue was purified by silica gel column chromatography to give 7a-7n.
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Representative procedure for PPh3AuOTf-catalyzed rearrangement reaction of
glycosyl alkynoic -ketoesters on a 1 mmol scale. To a solution of 3b (719 mg; 1.0 mmol)
and freshly activated 4 Å MS (1.0 g) in anhydrous CH2Cl2 (10 mL) at room temperature was
added the freshly prepared solution of PPh3AuOTf in dry CH2Cl2 (0.02 M, 10 mL) under
argon. After stirring at room temperature for 2 h, the mixture was filtered and concentrated in
vacuo. The residue was purified by silica gel column chromatography (petroleum
ether/EtOAc: 6/1) to give 7b (582 mg, 81%) as a white solid.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((2-oxo-6-phenyl-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7a (57 mg, 74%, white solid, petroleum
ether/EtOAc: 6/1): mp = 90–93 ºC ; [α]2D0 = –4.1 (c 0.51, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 8.06–7.73 (m, 10 H), 7.57–7.30 (m, 15 H), 6.43 (d, J = 2.0 Hz, 1 H), 6.03 (t, J = 9.2 Hz, 1
H), 5.86–5.82 (m, 2 H), 5.74 (t, J = 9.6 Hz, 1 H), 5.60 (d, J = 7.6 Hz, 1 H, H-1), 4.70 (dd, J =
13
2.4, 12.4 Hz, 1 H), 4.50–4.38 (m, 2 H); C{1H} NMR (CDCl3, 150 MHz) δ 168.3, 166.2,
165.8, 165.3, 165.1, 163.5, 161.3, 133.9, 133.8, 133.7, 133.6, 131.4, 130.9, 130.1, 130.0,
129.9, 129.3, 129.1, 128.8, 128.7, 128.6, 128.5, 126.0, 97.7, 97.4 (C-1), 92.3, 73.6, 72.6, 71.2,
69.1, 63.0; HRMS (ESI) m/z calcd for C45H34O12Na [M + Na]+ 789.1948, found 789.1943.
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(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((6-ethyl-2-oxo-2H-pyran-4-
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yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7b (60 mg, 83%, white solid,
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petroleum ether/EtOAc: 6/1): mp = 79–81 ºC ; [α]2D0 = +39.7 (c 0.80, CHCl3); H NMR (400
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MHz, CDCl3) δ 8.05–7.83 (m, 8 H), 7.59–7.29 (m, 12 H), 5.99 (t, J = 9.2 Hz, 1 H), 5.80–5.76
(m, 2 H), 5.73–5.68 (m, 2 H), 5.52 (d, J = 7.6 Hz, 1 H, H-1), 4.67 (dd, J = 2.4, 12.0 Hz, 1 H),
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4.47–4.33 (m, 2 H), 2.42 (q, J = 7.6 Hz, 2 H), 1.14 (t, J = 7.6 Hz, 3 H); C{1H} NMR (100
MHz, CDCl3) δ 168.3, 168.2, 166.2, 165.8, 165.3, 165.1, 164.3, 133.9, 133.8, 133.6, 133.5,
130.1, 129.9, 129.3, 128.8, 128.7, 128.6, 128.5, 98.6, 97.2 (C-1), 91.4, 73.4, 72.5, 71.1, 69.0,
63.0, 27.0, 10.8; HRMS (ESI) m/z calcd for C41H34O12Na [M + Na]+ 741.1948, found
741.1949.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((6-methyl-2-oxo-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7c (50 mg, 71%, white solid, petroleum
ether/EtOAc: 6/1): mp = 70–72 ºC ; [α]2D0 = +34.5 (c 0.48, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 8.06–7.84 (m, 8 H), 7.58–7.27 (m, 12 H), 6.02 (t, J = 9.2 Hz, 1 H), 5.82–5.70 (m, 4 H), 5.56
(d, J = 7.6 Hz, 1 H, H-1), 4.67 (dd, J = 2.4, 12.0 Hz, 1 H), 4.48–4.37 (m, 2 H), 2.11 (s, 3 H);
13C{1H} NMR (150 MHz, CDCl3) δ 168.2, 166.2, 165.8, 165.3, 165.0, 164.2, 163.3, 133.8,
133.7, 133.6, 133.5, 130.0, 129.9, 129.3, 128.8, 128.7, 128.6, 128.5, 100.1, 97.2 (C-1), 91.3,
73.4, 72.5, 71.2, 69.0, 63.0, 20.0; HRMS (ESI) m/z calcd for C40H32O12Na [M + Na]+
727.1791, found 727.1793.
(2R,3R,4S,5R,6S)-2-((Benzoyloxy)methyl)-6-((2-oxo-6-pentyl-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7d (43 mg, 57%, white solid,
petroleum ether/EtOAc: 6/1): mp = 65–67 ºC ; [α]2D0 = +33.2 (c 0.32, CHCl3); H NMR (400
1
MHz, CDCl3) δ 8.05–7.83 (m, 8 H), 7.59–7.29 (m, 12 H), 5.99 (t, J = 9.2 Hz, 1 H), 5.80–5.76
(m, 2 H), 5.73–5.68 (m, 2 H), 5.52 (d, J = 7.6 Hz, 1 H, H-1), 4.67 (dd, J = 2.4, 12.0 Hz, 1 H),
4.48–4.43 (m, 2 H), 2.37 (t, J = 8.0 Hz, 2 H), 2.41–2.32 (m, 2H), 1.58–1.53 (m, 2 H), 1.31–
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1.24 (m, 4 H), 0.86 (t, J = 7.2 Hz, 3 H); C{1H} NMR (150 MHz, CDCl3) δ 168.2, 167.2,
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166.2, 165.8, 165.3, 165.1, 164.4, 133.9, 133.8, 133.7, 133.6, 130.1, 130.0, 129.3, 128.8,
128.7, 128.6, 128.5, 99.4, 97.3 (C-1), 91.4, 73.5, 72.5, 71.1, 69.0, 63.0, 33.8, 31.2, 26.4, 22.4,
14.0; HRMS (ESI) m/z calcd for C44H40O12Na [M + Na]+ 783.2417, found 783.2421.
(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((2-oxo-6-phenyl-2H-pyran-4-
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yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7e (64 mg, 83%, white solid, petroleum
ether/EtOAc: 6/1): mp = 85–89 ºC ; [α]2D0 = +24.4 (c 0.31, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 8.11–7.85 (m, 10 H), 7.66–7.28 (m, 15 H), 6.69 (d, J = 2.0 Hz, 1 H), 6.17 (t, J = 10.0 Hz, 1
H), 6.07–6.03 (m, 2 H), 5.93–5.90 (m, 2 H), 4.70–4.65 (m, 1 H), 4.52–4.45 (m, 2 H); 13C
NMR (100 MHz, CDCl3) δ 167.3, 166.2, 165.7, 165.5, 165.4, 163.3, 161.5, 134.1, 133.9,
133.7, 133.4, 131.5, 131.0, 130.1, 130.0, 129.9, 129.8, 129.6, 129.2, 128.9, 128.8, 128.7,
128.6, 126.0, 97.2 (1JC1,H1 = 170.5 Hz), 95.7 (1JC1,H1 = 177.0 Hz), 93.0 (1JC1,H1 = 170.5 Hz),
70.8, 69.5, 66.3, 62.7; HRMS (ESI) m/z calcd for C45H34O12Na [M + Na]+ 789.1948, found
789.1946.
(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((6-ethyl-2-oxo-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7f (58 mg, 80%, white solid, petroleum
ether/EtOAc: 6/1): mp = 72–73 ºC ; [α]2D0 = +3.6 (c 0.94, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 8.09–7.85 (m, 8 H), 7.66–7.27 (m, 12 H), 6.15 (t, J = 10.0 Hz, 1 H), 6.02–5.98 (m, 2 H),
5.91 (d, J = 2.0 Hz, 1 H), 5.85 (br s, 2 H), 4.65 (dd, J = 2.0, 12.0 Hz, 1 H), 4.49–4.39 (m, 2 H),
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2.53 (q, J = 7.6 Hz, 2 H), 1.25 (t, J = 7.6 Hz, 3 H); C NMR (150 MHz, CDCl3) δ 168.5,
167.3, 166.1, 165.7, 165.5, 165.4, 164.1, 134.1, 133.8, 133.7, 133.4, 130.1, 130.0, 129.9,
129.8, 129.6, 128.9, 128.8, 128.7, 128.6, 128.5, 98.2 (1JC1,H1 = 173.4 Hz), 95.5 (1JC1,H1
=
176.4 Hz), 92.1 (1JC1,H1 = 169.8 Hz), 70.7, 69.5, 66.3, 62.6, 27.1, 10.9; HRMS (ESI) m/z
calcd for C41H34O12Na [M + Na]+ 741.1948, found 741.1946.
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(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((6-methyl-2-oxo-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7g (52 mg, 74%, white solid, petroleum
ether/EtOAc: 6/1): mp = 85–87 ºC ; [α]2D0 = +5.0 (c 0.40, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 8.09–7.84 (m, 8 H), 7.66–7.27 (m, 12 H), 6.13 (t, J = 10.0 Hz, 1 H), 6.02 (d, J = 1.2 Hz, 1
H), 5.98 (dd, J = 2.8, 10.4 Hz, 1 H), 5.90 (d, J = 2.0 Hz, 1 H), 5.84 (br s, 2 H), 4.65 (dd, J =
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2.0, 12.0 Hz, 1 H), 4.47 (dd, J = 5.2, 12.0 Hz, 1 H), 4.42–4.38 (m, 1 H), 2.24 (s, 3 H); C
NMR (150 MHz, CDCl3) δ 167.2, 166.2, 165.7, 165.5, 165.4, 164.1, 163.7, 134.1, 133.9,
133.7, 133.5, 130.1, 130.0, 129.9, 129.8, 129.6, 128.9, 128.8, 128.7, 128.6, 99.7 (1JC1,H1
=
174.0 Hz), 95.5 (1JC1,H1 = 175.8 Hz), 92.0 (1JC1,H1 = 171.0 Hz), 70.7, 69.5, 69.4, 66.3, 62.6,
20.2; HRMS (ESI) m/z calcd for C40H32O12Na [M + Na]+ 727.1791, found 727.1792.
(2R,3R,4S,5S,6R)-2-((Benzoyloxy)methyl)-6-((2-oxo-6-pentyl-2H-pyran-4-
yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate 7h (46 mg, 60%, white solid,
petroleum ether/EtOAc: 6/1): mp = 58–60 ºC ; [α]2D0 = +5.3 (c 0.34, CHCl3); H NMR (400
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MHz, CDCl3) δ 8.09–7.84 (m, 8 H), 7.66–7.27 (m, 12 H), 6.14 (t, J = 10.0 Hz, 1 H), 6.02–
5.98 (m, 2 H), 5.90 (d, J = 2.4 Hz, 1 H), 5.85 (m, 2 H), 4.66 (dd, J = 2.0, 12.0 Hz, 1 H), 4.49–
4.39 (m, 2 H), 2.48 (t, J = 8.0 Hz, 2 H), 1.74–1.64 (m, 2 H), 1.37–1.33 (m, 4 H), 0.93 (t, J =
6.8 Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ 167.5, 167.3, 166.2, 165.7, 165.5, 165.4, 164.2,
134.1, 133.9, 133.7, 133.4, 130.0, 129.9, 129.8, 129.7, 128.9, 128.8, 128.7, 128.6, 99.0
(1JC1,H1 = 175.5 Hz), 95.6 (1JC1,H1 = 176.5 Hz), 92.1 (1JC1,H1 = 172.0 Hz), 70.7, 69.6, 69.5, 66.3,
62.6, 34.0, 31.3, 26.5, 22.5, 14.1; HRMS (ESI) m/z calcd for C44H40O12Na [M + Na]+
783.2417, found 783.2418.
(2R,3R,4S,5R,6R)-2-Methyl-6-((6-methyl-2-oxo-2H-pyran-4-yl)oxy)tetrahydro-2H-
pyran-3,4,5-triyl tribenzoate 7i (47 mg, 80%, white solid, petroleum ether/EtOAc: 6/1): mp
= 76–78 ºC ; [α]2D0 = –164.4 (c 0.57, CHCl3); H NMR (400 MHz, CDCl3) δ 8.11–7.78 (m, 6
1
H), 7.63 (t, J = 7.6 Hz, 1 H), 7.54–7.36 (m, 6 H), 7.28–7.24 (m, 2 H), 5.97 (dd, J = 7.6, 10.4
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Hz, 1 H), 5.82 (d, J = 0.8 Hz, 1 H), 5.78 (d, J = 3.2 Hz, 1 H), 5.68 (d, J = 2.0 Hz, 1 H), 5.64
(dd, J = 3.6, 10.4 Hz, 1 H), 5.41 (d, J = 8.0 Hz, 1 H, H-1), 4.25 (q, J = 6.4 Hz, 1 H), 2.18 (s, 3
H), 1.39 (d, J = 6.4 Hz, 3 H); 13C{1H} NMR (150 MHz, CDCl3) δ 168.5, 166.0, 165.8, 165.3,
164.7, 163.2, 133.8, 133.7, 133.6, 130.2, 129.9, 129.2, 129.0, 128.8, 128.7, 128.6, 128.5,
100.4, 97.7 (C-1), 91.2, 71.8, 71.0, 70.6, 69.0, 20.1, 16.4; HRMS (ESI) m/z calcd for
C33H28O10Na [M + Na]+ 607.1580, found 607.1583.
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(2R,3S,4S,5S,6S)-2-Methyl-6-((6-methyl-2-oxo-2H-pyran-4-yl)oxy)tetrahydro-2H-
pyran-3,4,5-triyl tribenzoate 7j (45 mg, 78%, white solid, petroleum ether/EtOAc: 6/1): mp
= 62–64 ºC ; [α]2D0 = +41.0 (c 0.71, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.12–7.83 (m, 6 H),
7.66–7.28 (m, 9 H), 6.01 (br s, 1 H), 5.89 (dd, J = 3.6, 10.4 Hz, 1 H), 5.84 (d, J = 1.6 Hz, 1 H),
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5.79–5.72 (m, 3 H), 4.17–4.10 (m, 1 H), 2.28 (s, 3 H), 1.37 (d, J = 6.0 Hz, 3 H); C NMR
(100 MHz, CDCl3) δ 167.4, 165.7, 165.6, 164.4, 163.4, 134.0, 133.7, 133.6, 130.2, 129.9,
129.1, 128.9, 128.8, 128.7, 128.5, 100.0 (1JC1,H1 = 172.5 Hz), 95.6 (1JC1,H1 = 175.5 Hz), 91.7
(1JC1,H1 = 173.0 Hz), 71.1, 69.8, 69.4, 68.8, 20.2, 17.8; HRMS (ESI) m/z calcd for
C33H28O10Na [M + Na]+ 607.1580, found 607.1583.
(2R,3R,4R,5R,6S)-2-(Acetoxymethyl)-6-((6-methyl-2-oxo-2H-pyran-4-yl)oxy)-5-
(((2,2,2-trichloroethoxy)carbonyl)amino)tetrahydro-2H-pyran-3,4-diyl diacetate 7k (45
mg, 76%, white solid, petroleum ether/EtOAc: 3/1): mp = 92–94 ºC ; [α]2D0 = +4.7 (c 0.70,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.82 (br s, 1 H), 5.72 (d, J = 9.2 Hz, 1H, NH), 5.61 (d,
J = 2.0 Hz, 1 H), 5.42 (d, J = 3.2 Hz, 1 H), 5.31–5.25 (m, 2 H, H-1), 4.72 (s, 2 H), 4.19–4.09
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(m, 4 H), 2.20 (s, 3 H), 2.17 (s, 3 H), 2.07 (s, 3 H), 2.01 (s, 3 H); C{1H} NMR (150 MHz,
CDCl3) δ 170.7, 170.6, 170.3, 168.6, 164.8, 163.3, 154.5, 100.3, 97.5 (C-1), 95.7, 91.1, 74.6,
71.8, 69.7, 66.5, 61.6, 52.1, 20.8, 20.7, 20.1; HRMS (ESI) m/z calcd for C21H24O12NCl3Na [M
+ Na]+ 610.0262, found 610.0258.
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(2S,3R,4S,5R,6R)-5-(Benzyloxy)-6-((benzyloxy)methyl)-4-((tert-
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butyldimethylsilyl)oxy)-2-((6-ethyl-2-oxo-2H-pyran-4-yl)oxy)tetrahydro-2H-pyran-3-yl
benzoate 7l (50 mg, 71%, pale yellow syrup, petroleum ether/EtOAc: 4/1): [α]2D0 = +18.9 (c
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1.13, CHCl3); H NMR (400 MHz, CDCl3) δ 8.03–8.01 (m, 2 H), 7.58 (t, J = 7.2 Hz, 1 H),
7.45 (t, J = 7.6 Hz, 2 H), 7.33–7.20 (m, 10 H), 5.70 (d-like, J = 2.0 Hz, 1 H), 5.59 (d-like, J =
2.0 Hz, 1 H), 5.43 (dd, J = 7.6, 8.8 Hz, 1 H, H-2), 5.14 (d, J = 7.6 Hz, 1 H, H-1), 4.82 (d-like,
J = 11.2 Hz, 1 H), 4.63–4.47 (m, 3 H), 4.01 (t, J = 8.4 Hz, 1 H, H-3), 3.78–3.73 (m, 3 H),
3.68–3.64 (m, 1 H), 2.39 (q, J = 7.6 Hz, 2 H), 1.11 (t, J = 7.6 Hz, 3 H), 0.79 (s, 9 H), 0.01 (s,
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3 H), -0.14 (s, 3 H); C{1H} NMR (150 MHz, CDCl3) δ 168.8, 167.8, 165.2, 164.8, 137.9,
137.8, 133.5, 130.0, 129.7, 128.6, 128.5, 127.9, 127.8, 127.6, 99.0, 97.6 (C-1), 91.2, 78.1,
76.0, 75.1, 74.9, 73.7, 68.3, 27.0, 25.8, 17.9, 10.9, -4.0, -4.2; HRMS (ESI) m/z calcd for
C40H48O9SiNa [M + Na]+ 723.2965, found 723.2966.
(2R,3R,4R,5S)-2-((Benzoyloxy)methyl)-5-((6-ethyl-2-oxo-2H-pyran-4-
yl)oxy)tetrahydrofuran-3,4-diyl dibenzoate 7m (43 mg, 74%, colorless syrup, petroleum
ether/EtOAc: 5/1): [α]2D0 = –6.2 (c 0.37, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.02–7.99 (m,
4 H), 7.93–7.91 (m, 2 H), 7.62–7.52 (m, 3 H), 7.46–7.34 (m, 6 H), 5.94 (dd, J = 5.2, 7.2 Hz, 1
H), 5.89 (d, J = 4.8 Hz, 1 H), 5.86 (s, 1 H, H-1), 5.68 (d-like, J = 2.4 Hz, 1 H), 5.62 (m, 1 H),
4.88–4.79 (m, 2 H), 4.44 (dd, J = 4.0, 12.0 Hz, 1 H), 2.41 (q, J = 7.6 Hz, 2 H), 1.15 (t, J = 7.6
Hz, 3 H); 13C{1H} NMR (150 MHz, CDCl3) δ 167.8, 167.7, 166.0, 165.6, 165.3, 164.5, 134.1,
133.9, 133.4, 130.1, 130.0, 129.9, 129.6, 128.8, 128.7, 128.6, 128.5, 102.8 (C-1), 98.5, 91.5,
80.8, 75.4, 71.3, 63.3, 27.0, 10.8; HRMS (ESI) m/z calcd for C33H28O10Na [M + Na]+
607.1580, found 607.1578.
6-Ethyl-4-(((3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-
2H-pyran-2-yl)oxy)-2H-pyran-2-one 7n (55 mg, 83%, / = 2/3, yellow syrup, petroleum
ether/EtOAc: 6/1): [α]2D0 = +20.3 (c 0.30, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.38–7.27 (m,
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18 H), 7.16–7.10 (m, 2 H), 5.89 (d, J = 2.0 Hz, 0.4 H), 5.73 (d, J = 2.0 Hz, 0.6 H), 5.63 (d, J =
2.4 Hz, 0.4 H), 5.59 (d, J = 2.0 Hz, 0.6 H), 5.37 (d, J = 3.6 Hz, 0.4 H, H-1), 5.01 (m, 1 H),
4.92–4.78 (m, 4 H), 4.64–4.59 (m, 1.4 H), 4.55–4.41 (m, 2 H), 4.06 (t, J = 9.6 Hz, 0.6 H),
3.84–3.69 (m, 4 H), 3.65–3.62 (m, 0.6 H), 3.59–3.53 (m, 1 H), 2.53–2.47 (m, 2 H), 1.24–1.19
(m, 3 H); 13C{1H} NMR (150 MHz, CDCl3) δ 168.8, 168.4, 167.9, 167.8, 164.9, 138.7, 138.4,
138.1, 138.0, 137.9, 137.8, 137.7, 137.6, 128.8, 128.7, 128.6, 128.5, 128.4, 128.2, 128.1,
128.0, 127.9, 99.7, 98.8, 98.7, 95.5, 91.4, 91.3, 84.6, 81.8, 81.5, 79.2, 76.9, 76.1, 76.0, 75.6,
75.5, 75.4, 75.3, 74.0, 73.8, 73.7, 72.1, 68.1, 67.8, 27.1, 27.0, 11.0, 10.9; HRMS (ESI) m/z
calcd for C41H42O8Na [M + Na]+ 685.2777, found 685.2778.
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6-Methyl-4-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-
pyran-2-yl)oxy)-2H-pyran-2-one 8.12 To a solution of compound 7c (49 mg, 0.07 mmol) in
dichloromethane and methanol (1/2, v/v, 9 mL) was added a solution of NaOMe in MeOH
(0.5 M, 63 μL). After stirring at room temperature for 24 h, the mixture was neutralized with
Amberlite IR120 H+ resin. After filtration, the filtrate was concentrated in vacuo. The residue
was purified by silica gel column chromatography (CH2Cl2/MeOH: 10/1 → 5/1) to give 8 (19
mg, 95%) as a white solid: [α]2D0 = –91.5 (c 0.31, H2O); H NMR (400 MHz, CD3OD) δ 6.13
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(d, J = 1.2 Hz, 1 H), 5.69 (d, J = 2.0 Hz, 1 H), 5.03 (d, J = 7.6 Hz, 1 H, H-1), 3.88 (dd, J = 2.4,
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12.4 Hz, 1 H), 3.69 (dd, J = 5.2, 12.0 Hz, 1 H), 3.51–3.38 (m, 4 H), 2.25 (s, 3 H); C{1H}
NMR (150 MHz, CD3OD) δ 171.5, 167.4, 164.8, 101.5, 100.8, 91.7, 78.5, 77.7, 74.4, 70.9,
62.2, 19.7; HRMS (ESI) m/z calcd for C12H16O8Na [M + Na]+ 311.0743, found 311.0741.
6-Ethyl-4-hydroxy-2H-pyran-2-one 9.6c To a solution of 3b (72 mg, 0.10 mmol), 4-
penten-1-ol 4a (10.3 μL, 0.10 mmol), and freshly activated 4 Å MS (100 mg) in anhydrous
CH2Cl2 (1.0 mL) at room temperature was added the freshly prepared solution of PPh3AuOTf
in anhydrous CH2Cl2 (0.02 M, 1.0 mL) under argon. After stirring at room temperature for 2 h,
the mixture was filtered and concentrated in vacuo. The residue was purified by silica gel
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column chromatography (petroleum ether/EtOAc: 15/1→0:1) to give 5a (33 mg, 50%) as a
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white solid, 7b (14 mg, 19%) as a white solid, and 9 (10 mg, 71%) as a white solid. 9: H
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= 7.6 Hz, 2 H), 1.21 (t, J = 7.6 Hz, 3 H); C{1H} NMR (CDCl3, 100 MHz) δ 173.0, 168.6,
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168.5, 100.8, 89.9, 27.0, 11.0; HRMS (EI) m/z calcd for C7H8O3 [M]+ 140.0473, found
140.0471.
Competitive reaction between the rearrangement reaction and the glycosylation. To
a solution of 3k (59 mg, 0.10 mmol), 10 (117 mg, 0.15 mmol), and freshly activated 4 Å MS
(200 mg) in anhydrous CH2Cl2 (2.0 mL) at room temperature was added the freshly prepared
solution of PPh3AuOTf in anhydrous CH2Cl2 (0.02 M, 2.0 mL) under argon. After stirring at
room temperature for 2 h, the mixture was filtered and concentrated in vacuo. The residue was
purified by silica gel column chromatography (petroleum ether/EtOAc: 6/1→3:1) to give 7k
(43 mg, 73%) as a white solid and 7c (15 mg, 21%) as a white solid.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at
DOI: 10.1021/
Copies of NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: yangyou@ecust.edu.cn
ORCID
You Yang: 0000-0003-4438-2162
Notes
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