Total Syntheses of Aturanosides A and B

Article abstract of DOI:10.1021/acs.orglett.1c02244

Total syntheses of aturanosides A and B, two antiangiogenic anthraquinone glycosides, have been achieved in an expeditious manner, highlighting anthraquinone synthesis, phenol glycosylation, α-d-glucosaminoside installation, and judicious use of protectin

Full text of DOI:10.1021/acs.orglett.1c02244

pubs.acs.org/OrgLett
Letter
Total Syntheses of Aturanosides A and B
Yingjie Wang and Biao Yu*
Cite This: https://doi.org/10.1021/acs.orglett.1c02244
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Total syntheses of aturanosides A and B, two antiangiogenic
anthraquinone glycosides, have been achieved in an expeditious manner,
highlighting anthraquinone synthesis, phenol glycosylation, α-D-glucosaminoside
installation, and judicious use of protecting groups.
turanosides A and B [1 and 2, respectively (Figure 1)],
two novel anthraquinone glycosides, were isolated from
A
soil-derived Streptomyces sp. RK88-1441 by Ahn and co-
workers in 2018.1 The aglycone of aturanosides, named R1128
A (3), together with three congeners bearing various alkyl
groups at C8, has already been identified from Streptomyces sp.
No. 1128 by Hori et al. in 1993.2,3 The N-acetyl-α-D-
glucosamino-(1→2)-α-L-rhamnoside fragment in 1 has never
been found in secondary metabolites; nevertheless, it occurs in
a few exopolysaccharides of bacteria.4−9 Interestingly, the
glycosides (1 and 2) showed no cytotoxicity against human
umbilical vein endothelial cells (HUVECs) but significantly
suppressed vascular endothelial growth factor (VEGF)-
induced tube formation and invasion of HUVECs,1 and the
aglycone (3) significantly inhibited the binding of estrogen to
its receptor with IC50 values of ∼0.1 μM.3,10 In 2012, Iwao et
al. reported the synthesis of R1128 A (3) and its congeners,
using iterative ortho lithiation of 2-(4-methoxyphenyl)-4,4-
dimethyloxazoline as the key reactions.11 To study in depth the
antiangiogenic activity of the glycosides (1 and 2) and the
nonsteroidal estrogen receptor antagonistic activity of the
aglycone (3), both relevant to the antitumor activities, we
embarked on the synthesis of the anthraquinone and its
glycosides. Here, we report an efficient approach to the
synthesis of aturanosides A and B (1 and 2, respectively).
A collective synthesis of the glycosides called for a linear
strategy to install the sugar residues on the aglycone.12 Thus,
anthraquinone derivative A, rhamnose donor B, and glucos-
amine donor C became requisite building blocks (Figure 1), in
which the judicious choice of the protecting groups was
necessary to ensure regioselective glycosylation at the
anthraquinone C6-OH and stereoselective glycosylations to
furnish the 1,2-trans-α-L-rhamnoside and 1,2-cis-α-D-glucosa-
minoside linkages. It is known that the glycosylation of
electron-deficient phenols is always associated with specific
problems, due to the low nucleophilicity of the hydroxyl group
Figure 1. Aturanosides A (1) and B (2) and R1128 A (3) and the
retrosynthetic plan.
and the poor solubility of the substrate in common
glycosylation solvents.13 Therefore, rhamnose donors (B)
bearing a variety of leaving groups were planned to be used in
the synthesis. Anthraquinone aglycone A, bearing protecting
Received: July 5, 2021
https://doi.org/10.1021/acs.orglett.1c02244
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
groups at C1-OH and C3-OH, could be prepared by an
intramolecular Friedel−Crafts acylation of hydroxyphthalide
D, which could be accessed from N,N-diethylbenzamide E via
iterative ortho lithiation followed by alkylation with 1-
iodopropane and addition with aldehyde F.
Our synthesis commenced with alkylation of 4-(4-
methoxybenzyloxy)benzamide 4 (Scheme 1), which was
lithiation directed by the N,N-diethylamide group took place
preferentially at the o-phenyl carbon in 5 rather than the
benzylic carbons in the presence of sec-BuLi (1.1 equiv),
resulting in a 68% yield of monodeuterated derivative 13.
Further lithiation at the benzylic carbon of the PMB residue
occurred in the presence of excess sec-BuLi (2.0 equiv) to give
14; nevertheless, deuteration at the lateral alkyl carbon was not
observed.
Thus, treatment of amide 5 with sec-BuLi (1.2 equiv) and
TMEDA in THF at −72 °C, followed by addition of 3,5-
dibenzyloxybenzaldehyde 6a, led to the desired adduct, which
underwent lactonization under the action of aqueous
CF3COOH to provide phthalide 7a in a satisfactory 70%
yield.11,14 Attempts at reductive ring opening of the lactone in
7a led to preferential cleavage of the phenolic benzyl ethers.
Gratifyingly, phthalide 7a could be smoothly oxidized to
hydroxyphthalide 8a in the presence of oxygen under basic
conditions;19 subsequent treatment with AcOH under reflux
led to selective removal of the PMB group,20 which gave 9a in
good yield (80% for two steps). This rise of the oxidation state
would allow intramolecular Friedel−Crafts acylation to furnish
the desired anthraquinone (i.e., 10a). However, subjecting 9a
(or 8a) to various Friedel−Crafts conditions resulted in
mixtures. A relatively clean reaction of 9a was realized under
the action of TFAA (20 equiv) and TFA in CH2Cl2 at rt,
leading to two major products identified as 11 (45%) and 12
(15%), in which the C1-O-benzyl group was cleaved and
migrated to C2, respectively.21 In fact, the cleavage and O → C
migration (via the resultant benzyl cation) of phenolic benzyl
groups have been well appreciated.22−25 To avoid these side
reactions, we replaced the benzyl groups with 4-trifluorome-
thylbenzyl (TFBn) groups;26 the electron-withdrawing para-
substituted trifluoromethyl group would destabilize the
corresponding benzyl cation and thus disfavor the cleavage
and subsequent Friedel−Crafts alkylation reaction. Thus,
hydroxyphthalide 9b was prepared from benzamide 5 and
benzaldehyde 6b following the previous procedure for the
preparation of 9a (from 5 and 6a), in a slightly lower yield
(40% vs 56% yield for four steps). To our delight, the desired
intramolecular Friedel−Crafts acylation of 9b took place
smoothly under the action of TFAA and TFA (CH2Cl2, rt),
providing anthraquinone 10b in a decent 76% yield without
detection of the side products derived from cleavage and
rearrangement of the TFBn groups.
With anthraquinone 10b being available in quantity (2 g
scale), we set out to explore the glycosylation of phenol 10b
with a panel of 2-O-acetyl-3,4-di-O-benzyl-L-rhamnopyranosyl
donors (i.e., 15−19) under various conditions (Table 1). First,
we examined the Mitsunobu glycosylation, which has been
found to be particularly useful for the glycosylation of
phenols;27 however, the reaction of 10b and lactol 15 did
not take place under the conventional Mitsunobu conditions
(entries 1 and 2). The gold(I)-catalyzed glycosylation with o-
alkynylbenzoate donors (e.g., 16) has been successfully applied
to the glycosylation of a wide variety of nucleophiles,28
including electron-deficient phenols.29,30 Unfortunately, the
glycosylation of 10b with donor 16 proceeded sluggishly in the
presence of PPh3AuNTf2 (entry 3), leading to coupled α-
rhamnoside 20 in only 42% yield even with heating (1 equiv of
PPh3AuNTf2, CH2Cl2, 45 °C; entry 4). This result testified to
the poor nucleophilicity of anthraquinone phenol 10b,
resulting in decomposition of the donor before glycosylation.
Trichloroacetimidate donor 17 was also found to be ineffective
Scheme 1. Construction of Anthraquinone Aglycone 10b
readily prepared from the inexpensive industrial material
methyl 4-hydroxybenzoate (see the Supporting Information).
Directed by the N,N-diethylamide group,14 ortho lithiation
took place in the presence of sec-BuLi (1.5 equiv) and
tetramethylethylenediamine (TMEDA) in THF at −72 °C;
subsequent addition of 1-iodopropane delivered the desired
alkylation product 5 in good yield.
It was reported that the ortho lithiation conditions could lead
to lateral lithiation at benzylic positions in the presence of an o-
alkyl substituent (such as in 5), and the regioselectivity could
be effected by variation of the directing group, solvents, and
additives.15−18 Thus, we performed deuterium labeling experi-
ments on benzamide 5 (Scheme 2) to examine whether the
N,N-diethylamide directing group and the 4-methoxybenzyl
(PMB) protecting group are compatible with the next ortho
lithiation−addition reaction (i.e., 5 + 6 → 7). Indeed, the
Scheme 2. Deuterium Labeling Experiments on Amide 5
B
https://doi.org/10.1021/acs.orglett.1c02244
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
than the trichloroacetimidate counterpart, was successful,
providing α-rhamnoside 20 in a high 92% yield in the
presence of either BF3·Et2O (0.5 equiv) or TMSOTf (0.5
equiv) at the expense of 3 equiv of the donor (entries 7 and 8).
We also tried the glycosylation with thioglycoside 19. It was
not surprising that the thioglycoside underwent decomposition
quickly in the presence of a strong promoter (i.e., NIS/TfOH)
with no evidence of glycosylation (entry 9). Excitingly, under a
mild promoter, i.e., MeOTf,33 the rate of activation on the
thioglycoside could match the rate of glycosylation with phenol
10b, leading to the desired 20 in 58% yield (entry 10), and the
yield was increased to 95% (at a gram scale) with a slight
decrease in the amount of MeOTf (from 9.0 to 5.0 equiv) and
an increase in the temperature (from rt to 45 °C; entry 11).
Subsequent removal of the 2-O-acetyl group in rhamnoside
20 with NaOMe in methanol gave 21 (95%) smoothly
(Scheme 3); installation of the α-glucosamine residue was then
examined (Table 2). 3,4,6-Tri-O-acetyl-2-azido-2-deoxy-gluco-
Table 1. Optimization of the Rhamnosylation on
Anthraquinone 10b
yield of 20
a
entry
donor
conditions
(%)
1
2
3
15 (3 equiv) PPh3, DEAD, DMF, rt
15 (3 equiv) PPh3, DEAD, THF, rt
NR
NR
28
16 (2 equiv) PPh3AuNTf2 (0.2 equiv), 4 Å MS,
CH2Cl2, rt
4
16 (3 equiv) PPh3AuNTf2 (1 equiv), 4 Å MS,
CH2Cl2, 45 °C
17 (3 equiv) BF3·Et2O (0.5 equiv), 4 Å MS,
CH2Cl2, 0 °C to rt
17 (3 equiv) TMSOTf (0.5 equiv), 4 Å MS,
CH2Cl2, 0 °C to rt
42
49
22
92
92
0
Table 2. Optimization of the Gold-Catalyzed Glycosylation
of 21 with Donor 22
5
a
b
6
entry
conditions
yield of 23 (%)
1
2
3
4
5
6
7
8
Ph3PAuNTf2, 4 Å MS, CH2Cl2, rt
Ph3PAuOTf, 4 Å MS, CH2Cl2, rt
Ph3PAuNTf2, 4 Å MS, toluene, rt
Ph3PAuOTf, 4 Å MS, toluene, rt
Ph3PAuNTf2, 4 Å MS, toluene, 40 °C
Ph3PAuOTf, 4 Å MS, toluene, 40 °C
Ph3PAuNTf2, 4 Å MS, toluene, 0 °C
Ph3PAuOTf, 4 Å MS, toluene, 0 °C
5
8
7
18 (3 equiv) BF3·Et2O (0.5 equiv), 4 Å MS,
CH2Cl2, rt
26
19
17
12
20
8
18 (3 equiv) TMSOTf (0.5 equiv), 4 Å MS,
CH2Cl2, rt
9
19 (3 equiv) NIS (3.6 equiv), TfOH, 4 Å MS,
CH2Cl2, rt
10
11
19 (3 equiv) MeOTf (9 equiv), 4 Å MS, CH2Cl2,
58
95
rt
c
83 (95)
19 (3 equiv) MeOTf (5 equiv), 4 Å MS, CH2Cl2,
45 °C
a
Reactions were performed with glycosyl donor 22 (0.03 mmol),
acceptor 21 (0.01 mmol), and a gold catalyst (2.5 μmol). Isolated
yield on a 0.01 mmol scale (c = 5.0 mM). The β-anomer was not
b
a
Isolated yields are given. The β anomer was not detected.
c
detected. Isolated yield on a 0.05 mmol scale (c = 20 mM).
in the glycosylation presented here, which underwent
decomposition faster than glycosylation, furnishing α-rhamno-
side 20 in 49% yield in the presence of BF3·Et2O (0.5 equiv)
and in 22% yield with TMSOTf (0.5 equiv) at 0 °C (entries 5
and 6, respectively).31,32 Gratifyingly, the glycosylation with N-
phenyltrifluoroacetimidate donor 18, which is less vulnerable
pyranosyl o-hexynylbenzoate 22 was chosen as the donor,
which has been found to be effective in highly α-selective
glycosylation under the action of PPh3AuOTf.34 However, in
the presence of either PPh3AuOTf or Ph3PAuNTf2 (0.25
Scheme 3. Completion of the Syntheses of Aturanosides A (1) and B (2)
C
https://doi.org/10.1021/acs.orglett.1c02244
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
equiv), the glycosylation of 21 with donor 22 hardly took place
in CH2Cl2 at rt (entries 1 and 2). When the CH2Cl2 was
replaced with toluene, the glycosylations improved slightly,
leading to the desired disaccharide 23 in <30% yields (entries 3
and 4). Increasing the temperature from rt to 40 °C led to
lower yields of coupled product 23 and faster decomposition of
the donor (entries 5 and 6). When the reaction temperature
was decreased to 0 °C, the glycosylation in the presence of
Ph3PAuNTf2 did not improve much (entry 7), but under the
action of Ph3PAuOTf, the reaction proceeded smoothly,
leading to 23 in 83% yield (entry 8); the yield was further
enhanced to 95% when the reaction was carried out at a higher
concentration (from 5.0 to 20 mM).
Synthesis, Shanghai Institute of Organic Chemistry,
University of Chinese Academy of Sciences, Chinese Academy
of Sciences, Shanghai 200032, China; School of Chemistry
and Materials Science, Hangzhou Institute for Advanced
Study, University of Chinese Academy of Sciences, Hangzhou
310024, China; orcid.org/0000-0002-3607-578X;
Email: byu@sioc.ac.cn
Author
Yingjie Wang − State Key Laboratory of Bioorganic and
Natural Products Chemistry, Center for Excellence in
Molecular Synthesis, Shanghai Institute of Organic
Chemistry, University of Chinese Academy of Sciences,
Chinese Academy of Sciences, Shanghai 200032, China
The azido group in disaccharide 23 could be reduced into
the requisite amino group under the hydrogenolysis conditions
for removal of the benzyl protecting groups. However,
subjecting 23 to a variety of hydrogenolysis conditions led to
complex mixtures. Thus, the azido group in 23 was selectively
reduced via Staudinger reduction with trimethylphosphine;
subsequent acetylation with acetic anhydride provided N-
acetylglucosamine derivative 24 in 74% yield. Simultaneous
cleavage of the TFBn and Bn groups in 24 via hydrogenolysis
was also not successful. Nevertheless, the phenolic TFBn
ethers were selectively cleaved via hydrogenolysis with 10%
Pd/C in DMF in the presence of a phosphate buffer solution
(pH 7.0), with the benzyl groups remaining unaffected.35,36 In
the absence of the TFBn ether, cleavage of the benzyl groups
occurred smoothly under the action of H2 over 10% Pd/C in
methanol in the presence of acetic acid, providing a mixture of
anthraquinone 25 and over-reduced anthrone 26 (1:1 25/26).
Colorless anthrone 26 was autoxidized completely to afford
yellow anthraquinone 25 in acetone-d6 in an NMR tube
overnight. In fact, treatment of the resultant mixture of
anthraquinone 25 and anthrone 26 with NaOMe (0.05 M) in
methanol in an oxygen atmosphere led to removal of the acetyl
groups and concomitant oxidation of 26, furnishing aturano-
side A (1) in an excellent 94% yield over three steps. By the
same token, aturanoside B (2) was synthesized from
anthraquinone rhamnoside 20 (89% over three steps). The
analytic data of synthetic 1 and 2 are identical to those
reported for natural aturanosides A and B.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c02244
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Shanghai Municipal Science and
Technology Major Project, the National Natural Science
Foundation of China (22031011 and 21621002), the Key
Research Program of Frontier Sciences of CAS (ZDBS-LY-
SLH030), and the National Key Research & Development
Program of China (2018YFA0507602) is acknowledged.
REFERENCES
■
(1) Jang, J.-P.; Hwang, G. J.; Jang, M.; Takahashi, S.; Ko, S.-K.;
Osada, H.; Jang, J.-H.; Ahn, J. S. Aturanosides A and B, glycosylated
anthraquinones with antiangiogenic activity from a soil-derived
Streptomyces species. J. Nat. Prod. 2018, 81, 2004−2009.
(2) Hori, Y.; Takase, S.; Shigematsu, N.; Goto, T.; Okuhara, M.;
Kohsaka, M. R1128 substances, novel non-steroidal estrogen-receptor
antagonists produced by a Streptomyces. II. Physico-chemical proper-
ties and structure determination. J. Antibiot. 1993, 46, 1063−1068.
(3) Hori, Y.; Abe, Y.; Ezaki, M.; Goto, T.; Okuhara, M.; Kohsaka, M.
R1128 substances, novel non-steroidal estrogen-receptor antagonists
produced by a Streptomyces. I. Taxonomy, fermentation, isolation and
biological properties. J. Antibiot. 1993, 46, 1055−1062.
In summary, total syntheses of aturanosides A and B, two
anthraquinone glycosides with promising antitumor activities,
have been achieved. The synthesis of the disaccharide
aturanoside A takes the longest path with linear 12 steps in
14% overall yield, while the synthesis of the monosaccharide
congener aturanoside B proceeds in nine steps in 21% overall
yield. The expeditious synthetic approach presented here
would allow easy access to analogues of these rare natural
products and thus facilitate in-depth studies of their biological
activities.
(4) L’vov, V. L.; Dashunin, V. M.; Ramos, E. L.; Shashkov, A. S.;
Dmitriev, B. A.; Kochetkov, N. K. Somatic antigens of Shigella: the
structure of the polysaccharide chain of Shigella boydii type 2
lipopolysaccharide. Carbohydr. Res. 1983, 124, 141−149.
(5) Backman-Marklund, I.; Jansson, P.-E.; Lindberg, B.; Henrichsen,
J. Structural studies of the capsular polysaccharide from Streptococcus
pneumoniae type 7A. Carbohydr. Res. 1990, 198, 67−77.
(6) Jansson, P.-E.; Lindberg, J.; Swarna Wimalasiri, K. M.;
Henrichsen, J. The structure of the capsular polysaccharide from
Streptococcus pneumoniae type 7B. Carbohydr. Res. 1991, 217, 171−
180.
(7) Zhang, J.; Yan, S.; Liang, X.; Wu, J.; Wang, D.; Kong, F. Practical
preparation of 2-azido-2-deoxy-β-D-mannopyranosyl carbonates and
their application in the synthesis of oligosaccharides. Carbohydr. Res.
2007, 342, 2810−2817.
(8) Ghosh, T.; Misra, A. K. Facile synthesis of the pentasaccharide
repeating unit of the cell wall O-antigen of Escherichia coli 19ab.
Carbohydr. Res. 2012, 362, 8−12.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c02244.
■
sı
Experimental details and NMR spectra (PDF)
(9) Ménová, P.; Sella, M.; Sellrie, K.; Pereira, C. L.; Seeberger, P. H.
Identification of the minimal glycotope of Streptococcus pneumoniae
7F capsular polysaccharide using synthetic oligosaccharides. Chem. -
Eur. J. 2018, 24, 4181−4187.
(10) Hori, Y.; Abe, Y.; Nishimura, M.; Goto, T.; Okuhara, M.;
Kohsaka, M. R1128 substances, novel non-steroidal estrogen-receptor
AUTHOR INFORMATION
Corresponding Author
■
Biao Yu − State Key Laboratory of Bioorganic and Natural
Products Chemistry, Center for Excellence in Molecular
D
https://doi.org/10.1021/acs.orglett.1c02244
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
antagonists produced by a Streptomyces. III. Pharmacological proper-
ties and antitumor activities. J. Antibiot. 1993, 46, 1069−1075.
(11) Fukuda, T.; Fukushima, K.; Sanai, S.; Iwao, M. Synthesis of
non-steroidal estrogen receptor antagonists R1128 A, B, C, and D via
an oxazoline-promoted iterative ortho-lithiation strategy. Bull. Chem.
Soc. Jpn. 2012, 85, 133−135.
(12) Yu, B.; Sun, J.; Yang, X. Assembly of naturally occurring
glycosides, evolved tactics, and glycosylation methods. Acc. Chem. Res.
2012, 45, 1227−1236.
(13) Jacobsson, M.; Malmberg, J.; Ellervik, U. Aromatic O-
glycosylation. Carbohydr. Res. 2006, 341, 1266−1281.
(14) de Silva, S. O.; Watanabe, M.; Snieckus, V. General route to
anthraquinone natural products via directed metalation of N,N-
diethylbenzamides. J. Org. Chem. 1979, 44, 4802−4808.
(15) Beak, P.; Tse, A.; Haawkins, J.; Chen, C.-W.; Mills, S. A
comparison of secondary and tertiary amides as directors of ortho and
adjacent benzylic lithiation and of asymmetric induction in ortho
lithiated benzamides. Tetrahedron 1983, 39, 1983−1989.
(16) Mills, R. J.; Taylor, N. J.; Snieckus, V. Directed ortho
metalation of N,N-diethylbenzamides. Silicon protection of ortho sites
and the o-methyl group. J. Org. Chem. 1989, 54, 4372−4385.
(17) Court, J. J.; Hlasta, D. J. Ortho versus adjacent-benzylic
directed lithiations of substituted N,N-diethylbenzamides. Tetrahedron
Lett. 1996, 37, 1335−1338.
(31) Song, G.; Liu, H.; Zhang, W.; Geng, M.; Li, Y. Synthesis and
biological evaluation of cytotoxic activity of novel anthracene L-
rhamnopyranosides. Bioorg. Med. Chem. 2010, 18, 5183−5193.
(32) Tietze, L. F.; Gericke, K. M.; Guntner, C. First total synthesis of
̈
the bioactive anthraquinone Kwanzoquinone C and related natural
products by a Diels−Alder approach. Eur. J. Org. Chem. 2006, 4910−
4915.
(33) Lönn, H. Synthesis of a tri- and a hepta-saccharide which
contain α-L-fucopyranosyl groups and are part of the complex type of
carbohydrate moiety of glycoproteins. Carbohydr. Res. 1985, 139,
105−113.
(34) Yang, Y.; Li, Y.; Yu, B. Total synthesis and structural revision of
TMG-chitotriomycin, a specific inhibitor of insect and fungal β-N-
acetylglucosaminidases. J. Am. Chem. Soc. 2009, 131, 12076−12077.
(35) Kumar, V. S.; Aubele, D. L.; Floreancig, P. E. Electron transfer
initiated heterogenerative cascade cyclizations: polyether synthesis
under nonacidic conditions. Org. Lett. 2002, 4, 2489−2492.
(36) Crawford, C.; Oscarson, S. Optimized conditions for the
palladium-catalyzed hydrogenolysis of benzyl and naphthylmethyl
ethers: preventing saturation of aromatic protecting groups. Eur. J.
Org. Chem. 2020, 3332−3337.
(18) Thayumanavan, S.; Basu, A.; Beak, P. Two different pathways
of stereoinformation transfer: asymmetric substitutions in the
(−)-sparteine mediated reactions of laterally lithiated N,N-diisoprop-
yl-o-ethylbenzamide and N-pivaloyl-o-ethylaniline. J. Am. Chem. Soc.
1997, 119, 8209−8216.
(19) Anderson, B. A.; Hansen, M. M.; Harkness, A. R.; Henry, C. L.;
Vicenzi, J. T.; Zmijewski, M. J. Application of a practical biocatalytic
reduction to an enantioselective synthesis of the 5H-2,3-benzodiaze-
pine LY300164. J. Am. Chem. Soc. 1995, 117, 12358−12359.
(20) Hodgetts, K. J.; Wallace, T. W. Cleavage or acetyl-de-alkylation
of 4-methoxybenzyl (MPM) ethers using acetic acid. Synth. Commun.
1994, 24, 1151−1155.
(21) Townsend, C. A.; Christensen, S. B.; Davis, S. G. Synthesis of
averufin and its role in aflatoxin B1 biosynthesis. J. Chem. Soc., Perkin
Trans. 1 1988, 839−861.
(22) Pratt, D. A.; de Heer, M. I.; Mulder, P.; Ingold, K. U. Oxygen-
carbon bond dissociation enthalpies of benzyl phenyl ethers and
anisoles. An example of temperature dependent substituent effects. J.
Am. Chem. Soc. 2001, 123, 5518−5526.
(23) Sagrera, G.; Seoane, G. Acidic rearrangement of (benzyloxy)-
chalcones: a short synthesis of Ahamanetin. Synthesis 2009, 4190−
4202.
(24) Luzzio, F. A.; Chen, J. Synthetically useful Brønsted acid-
promoted arylbenzyl ether → o-benzylphenol rearrangements. J. Org.
Chem. 2009, 74, 5629−5632.
(25) Kraus, G. A.; Chaudhary, D. Conversion of substituted benzyl
ethers to diarylmethanes. A direct synthesis of diarylbenzofurans.
Tetrahedron Lett. 2012, 53, 7072−7074.
(26) Gaunt, M. J.; Yu, J.; Spencer, J. B. Rational design of benzyl-
type protecting groups allows sequential deprotection of hydroxyl
groups by catalytic hydrogenolysis. J. Org. Chem. 1998, 63, 4172−
4173.
(27) Hain, J.; Rollin, P.; Klaffke, W.; Lindhorst, T. K. Anomeric
modification of carbohydrates using the Mitsunobu reaction. Beilstein
J. Org. Chem. 2018, 14, 1619−1636.
(28) Yu, B. Gold(I)-catalyzed glycosylation with glycosyl o-
alkynylbenzoates as donors. Acc. Chem. Res. 2018, 51, 507−516.
(29) Liao, J.-X.; Fan, N.-L.; Liu, H.; Tu, Y.-H.; Sun, J.-S. Highly
efficient synthesis of flavonol 5-O-glycosides with glycosyl ortho-
alkynylbenzoates as donors. Org. Biomol. Chem. 2016, 14, 1221−1225.
(30) Liu, X.; Wen, G.-E.; Liu, J.-C.; Liao, J.-X.; Sun, J.-S. Total
synthesis of scutellarin and apigenin 7-O-β-D-glucuronide. Carbohydr.
Res. 2019, 475, 69−73.
E
https://doi.org/10.1021/acs.orglett.1c02244
Org. Lett. XXXX, XXX, XXX−XXX