A NaI/H2O2-Mediated Sulfenylation and Selenylation of Unprotected Uracil and Its Derivatives

Article abstract of DOI:10.1021/acs.orglett.9b02183

An efficient iodide-catalyzed/hydrogen peroxide mediated sulfenylation and selenylation of unprotected uracil and its derivatives with simple thiols and diselenides was established. This coupling tolerates a broad variety of functional groups to provide d

Full text of DOI:10.1021/acs.orglett.9b02183

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
A NaI/H2O2‑Mediated Sulfenylation and Selenylation of Unprotected
Uracil and Its Derivatives
Xue-Dong Li,†,§ Yu-Ting Gao,†,‡,§ Ying-Jie Sun,†,‡ Xiao-Yang Jin,†,‡ Dong Wang,† Li Liu,†,‡
and Liang Cheng*,†,‡
†Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS
Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing
100190, China
‡University of Chinese Academy of Sciences, Beijing 100049, China
S
* Supporting Information
ABSTRACT: An efficient iodide-catalyzed/hydrogen peroxide mediated
sulfenylation and selenylation of unprotected uracil and its derivatives with
simple thiols and diselenides was established. This coupling tolerates a broad
variety of functional groups to provide diverse 5-sulfur/selenium-substituted
uracil derivatives in good to excellent yields (up to 93%).
C-5 substituted nucleobases and nucleosides consist of an
important class of compounds that are valuable nucleotide-
derived tools in molecular genetics and have played very
important roles in many therapeutic areas.1 In particular, 5-
sulfur/selenium-substituted uracil bases and nucleosides have a
wide range of applications as part of antivirals and anticancer
agents and as biological probes in phototherapy and photo-
cross-linking applications (Figure 1).2 For example, 5-phenyl-
Scheme 1. Previous Protocols for the Generation of 5-
Sulfur/Selenium-Substituted Uracil Derivatives (a, b) and
Our Approach (c)
Figure 1. Selected examples of biologically active 5-sulfur/selenium-
substituted uracil derivatives.
thiouracil (NSC210778) was identified as an effective inhibitor
for FUDR phosphorylase, mammalian thymidine phosphor-
ylase, DHUDase, and UrdPase,3 while its analogue 5-
(phenylthio)acyclouridine (AC1NA056) has been designed
to improve oral uridine bioavailability with excellent
pharmacokinetic properties for the treatment of cancer and
AIDS.4 Furthermore, selenocyanic acid with the selenide
functional group at the C5-position of pyrimidine has been
recognized as a potential hypoxic radiosensitizer and genomic
DNA label in vitro.5
In the literature, a substantial number of useful C−S/Se
bond formation methods have been described through base-
promoted coupling reactions of thiols,6 disulfides,7 Bunte
salts,8 selenols,9 or diselenides10 with prefunctionalized uracil
these methods are useful, most of them suffer from several
limitations. For example, protection groups at the N-1 and N-3
positions of uracil were required in the prefunctionalization
strategy; thus, unprotected uracil targets, like 5-phenyl-
thiouracil in Figure 1, were not rapidly prepared through this
approach.12 In addition, most of these methods involved toxic
̈
(eq (a), Scheme 1). Apart from this, Bronsted acid promoted
cross coupling of uracil with sulfenyl chloride is another
Received: June 25, 2019
pathway for the C−S bond construction (eq (b)).11 Although
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02183
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
basic/acidic reagents and harsh reaction or inert atmosphere
conditions. We were determined to improve current protocols
by delivering a C−S/Se bond construction transformation for
the facile preparation of 5-sulfur/selenium-substituted uracil
derivatives with environmentally benign starting materials and
reagents. Herein, we report our progress in the development of
an efficient oxidative dehydrogenative C−S/Se coupling with
uracil. It is worth noting that environmentally benign hydrogen
peroxide was used as the oxidant. Both thiols and diselenides
were effectively coupled with unprotected uracil and its
derivatives to afford the desired products in good to excellent
yields (eq (c)).
of this procedure were explored (Scheme 2). A variety of
substituted arylthiols 2a−i, fused aryl thiol 2j, and hetero-
Scheme 2. Substrate Scope of Thiols and Uracil Derivatives
in the Sulfenylation
Inspired by our previous work on iodide-catalyzed C−C/C−
N bond formation and chemical modulation of nucleic acids,13
we initiated an investigation with the coupling between uracil
1a with 4-methylphenylthiol 2a (Table 1). To our delight, the
Table 1. Optimization of the C−S Coupling Reaction
a
Conditions
entry
[I] (equiv)
oxidant (equiv)
temp (°C)
yield (%)
1
2
3
4
5
6
7
8
NaI (3)
KI (3)
TBHP (3)
TBHP (3)
TBHP (3)
DTBP (3)
O2 (1 atm)
H2O2 (3)
H2O2 (6)
H2O2 (9)
H2O2 (9)
H2O2 (9)
H2O2 (9)
100
100
100
100
100
100
50
100
100
100
100
100
100
81
51
66
32
NR
75
83
92
89
80
21
TBAI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (1)
NaI (0.5)
NaI (0.1)
NaI (0.5)
b
9
10
11
12
13
trace
trace
H2O2 (9)
a
Reaction conditions: uracil 1a (0.2 mmol, 22.4 mg, 1 equiv), 4-
methylphenylthiol 2a (0.3 mmol, 37.5 mg, 1.5 equiv), iodide source,
oxidant in DMSO (3 mL) at the designated temperature under open
b
air for 15 h. Isolated yields of 3a are given. NR: no reaction.
initial attempt with 3 equiv of NaI and TBHP as the oxidant
afforded the desired product 5-p-tolylthiouracil 3a in an
isolation yield of 81% (entry 1), indicating that this iodide-
catalyzed C−S bond formation was indeed applicable.
Switching the iodide source or oxidant led to inferior results
(entries 2−5). However, when hydrogen peroxide was used as
the oxidant, the coupling product 3a was obtained in a good
yield (75%) (entry 6). Contrary to other commonly employed
chemical oxidants, hydrogen peroxide does not produce
residues or gases and is an ideal oxidant for large-scale
production. Thus, we became determined to improve this
process, and further optimization led to the isolation of 3a in
80% yield upon performing the reaction with 50% of NaI
(entry 10). However, further decreasing the loading of NaI
impeded the coupling (entry 11). By comparison, the identical
reaction without iodide source or hydrogen peroxide resulted
in trace product (entries 12 and 13), indicating that both were
essential for this coupling reaction.
arylthiol 2k were treated with simple uracil 1a. The desired 5-
sulfururacils 3a−k were efficiently obtained through this
coupling reaction in good to excellent yields, although
electron-withdrawing groups (F/Cl/Br, 3g−i) did result in
moderate yields. X-ray crystal structure of the product 3e
confirmed the C−S construction (see the Supporting
Information for details). Notably, the 6-substituted products
were not detected in all cases. Additionally, this protocol was
applicable not only to natural uracil but also to its substituted
derivatives. For example, good yields of the 5-sulfur-substituted
products 3l−p were obtained with the N1/3- and/or C6-
substituted uracil. However, when 4-nitro- or trifluoromethyl-
substituted phenylthiols 2q−r or pyridinyl thiol 2s were used,
trace products were observed. Alkyl thiols 2t−u were also not
applicable for this transformation.
With this useful sulfenylation protocol of uracil in hand, we
further investigated the possibility of C−Se bond formation
with diselenides. It turned out that the NaI/H2O2 system could
After the establishment of the C−S coupling reaction
conditions, the substrate scope and functional group tolerance
B
DOI: 10.1021/acs.orglett.9b02183
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
also successfully install selenium groups at the C5 position
(Scheme 3). With a catalytic loading of NaI (10%), aryl (4a−
Scheme 4. Scale-up Experiments and Post-Functionalization
of Sulfenyl and Selenyl Uracil Products
Scheme 3. Substrate Scope of Diselenides and Uracil
Derivatives in the Selenylation
For the elucidation of the reaction mechanism, some
preliminary controlled experiments were performed (Scheme
5). When the sulfenylation was proceeded with 1,2-
Scheme 5. Control Experiments
j), fused aryl (4k), and alkyl (4l−m) diselenides were
efficiently coupled with natural uracil 1a and diverse
substituted uracil derivatives 1b−e, generating the correspond-
ing products 5a−s in excellent yields. Notably, the electronic
effects of the functional groups on the phenyl ring did not have
a significant impact to the yields. Gratifyingly, C6-substituted
uracils 1e−g upon reacting with diphenyl diselenide 4a
furnished the corresponding selenide derivatives 5q−r in
excellent yields. Significantly, this selective functionalization
could also be applied to sugar-substituted uracil, from which
the selenylation product 5s was obtained in an isolated yield of
72%.
The scale-up experiments were later conducted. To our
delight, the reaction afforded the products 3a and 5a in
moderate to good yield (Scheme 4, eqs (a, b)). Furthermore,
treatment of the compound 5o with magnesium monoperox-
yphthalate (MMPP) gave the selenone product 6 in high yield
(eq (c)).14
diphenyldisulfane 7 under standard conditions, a comparable
yield of 3a was obtained (eq (a)), which implied that the
sulfenylation and selenylation may undergo a similar
mechanism. A slight decrease of 5a was isolated in the
presence of TEMPO (eq (b)), indicating that a nonradical
pathway might be involved in the reaction. We also conducted
the standard selenylation in the presence of iodine and the
product 5a was isolated in a comparable yield, which suggested
that the generation of iodine may be involved in this
transformation (eq (c)).
While the exact mechanism awaits further elucidation, on
the basis of previous research and preceding experiments, a
plausible mechanism using diselenide as example is outlined in
Scheme 6. It is considered that the iodide was first oxidized by
H2O2 to iodine, which then activated the thiol or diselenide to
C
DOI: 10.1021/acs.orglett.9b02183
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Notes
Scheme 6. Proposed Reaction Mechanism
The authors declare the following competing financial
interest(s): Institute of Chemistry, Chinese Academy of
Sciences (ICCAS) has filed a patent on the discovery and
development of this method that are described in the paper
presented on January 29, 2019, at the National Intellectual
Property Administration (Chinese provisional patent applica-
tion no. 2019100843077).
ACKNOWLEDGMENTS
■
This work was supported by the National Key R&D Program
of China (2017YFA0208100 and 2016YFA0602900), National
Natural Science Foundation of China (91853124, 21778057,
and 21420102003), and Chinese Academy of Sciences.
REFERENCES
■
(1) Ahmadian, M.; Bergstrom, D. E. 5- Substituted Nucleosides in
Biochemistry and Biotechnology. In Modified Nucleosides: in
Biochemistry, Biotechnology and Medicine; Herdewijn, P., Eds.; Wiley-
VCH, 2008.
afford the highly electrophilic sulfonium or selenium cation
intermediate I.15 An electrophilic addition of uracil to these
cationoid reagents resulted in relatively unstable seleranium
cation II and/or iminium ion intermediate III,16 followed by
elimination of hydrogen iodide HI to afford the C-5-
substituted uridine products. It is reasonable to expect that
C-5 would be more nucleophilic than C-6 so that the
substitution afforded the C-5-substituted product exclusively.17
In conclusion, we have established a direct iodide/hydrogen
peroxide mediated sulfenylation/selenylation of natural uracil
and its derivatives. This operationally simple and scalable
approach showed excellent substrate scope and tolerance of a
diverse of functional groups and produced the corresponding
5-sulfur/selenium-substituted uracil derivatives in good to
excellent yields. Mechanistic studies have suggested that an
electrophilic substitution pathway may be involved in this
process.
́
́
(2) (a) Pollum, M.; Martínez-Fernandez, L.; Crespo-Hernandez, C.
E. Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-
Analogues in Solution. In Photoinduced Phenomena in Nucleic Acids I;
Barbatti, M., Borin, A. C., Ullrich, S., Eds.; Topics in Current
Chemistry; Springer: Cham, 2015; Vol. 355, p 245. (b) Pridgeon, S.
W.; Heer, R.; Taylor, G. A.; Newell, D. R.; O’Toole, K.; Robinson,
M.; Xu, Y.-Z.; Karran, P.; Boddy, A. V. Thiothymidine combined with
UVA as a potential novel therapy for bladder cancer. Br. J. Cancer
2011, 104, 1869. (c) Favre, A. In Bioorganic Photochemistry, Vol. 1:
Photochemistry and the Nucleic Acids; Morrison, H., Eds.; Wiley-
Interscience: New York, 1990; p 379.
(3) (a) Baker, B. R.; Kelley, J. L. Irreversible enzyme inhibitors.
CLXXI. Inhibition of FUDR [5-fluoro-2’-deoxyuridine] phosphor-
ylase from Walker 256 rat tumor by 5-substituted uracils. J. Med.
Chem. 1970, 13, 461. (b) Baker, B. R.; Kelley, J. L. Irreversible
enzyme inhibitors. 188. Inhibition of mammalian thymidine
phosphorylase. J. Med. Chem. 1971, 14, 812. (c) Yoshimoto, M.;
Hansch, C. Correlation analysis of Baker’s studies on enzyme
inhibition. 2. Chymotrypsin, trypsin, thymidine phosphorylase,
uridine phosphorylase, thymidilate synthetase, cytosine nucleoside
deaminase, dihydrofolate reductase, malate, glutamate, lactate, and
glyceraldehyde-phosphate dehydrogenase. J. Med. Chem. 1976, 19, 71.
(d) Woodman, P. W.; Sarrif, A. M. Inhibition of nucleoside
phosphorylase cleavage of 5-fluoro-2’-deoxyuridine by 2,4-pyrimidi-
nedione derivatives. Biochem. Pharmacol. 1980, 29, 1059. (e) Abdul-
Ahad, P. G. The use of quantum chemical indices in the interpretation
of biological activity of some substituted uracils. J. Mol. Struct.:
THEOCHEM 1994, 306, 321.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02183.
Complete experimental details, characterization data for
the prepared compounds (PDF)
(4) Al Safarjalani, O. N.; Zhou, X.-J.; Rais, R. H.; Shi, J.; Schinazi, R.
F.; Naguib, F. N. M.; el Kouni, M. H. 5-(Phenylthio)acyclouridine: a
powerful enhancer of oral uridine bioavailability: relevance to
chemotherapy with 5-fluorouracil and other uridine rescue regimens.
Cancer Chemother. Pharmacol. 2005, 55, 541.
(5) Sosnowska, M.; Makurat, S.; Zdrowowicz, M.; Rak, J. 5-
Selenocyanatouracil: A Potential Hypoxic Radiosensitizer. Electron
Attachment Induced Formation of Selenium Centered Radical. J.
Phys. Chem. B 2017, 121, 6139.
Accession Codes
CCDC 1934844 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(6) (a) Fang, W.-P.; Cheng, Y.-T.; Cheng, Y.-R.; Cherng, Y.-J.
Synthesis of substituted uracils by the reactions of halouracils with
selenium, sulfur, oxygen and nitrogen nucleophiles under focused
microwave irradiation. Tetrahedron 2005, 61, 3107. (b) Akkilagunta,
V. K.; Reddy, V. P.; Rao, K. R. Recyclable Iron/Graphite Catalyst for
C-S Cross Coupling of Thiols with Aryl Halides under Ligand-Free
Conditions. Synlett 2010, 1260. (c) Amareshwar, V. Facile Route for
the Synthesis of Nucleobase Analogs. Synth. Commun. 2008, 39, 342.
(d) Dexheimer, T. S.; Rosenthal, A. S.; Luci, D. K.; Liang, Q.;
Villamil, M. A.; Chen, J.-J.; Sun, H.-M.; Kerns, E. H.; Simeonov, A.;
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: chengl@iccas.ac.cn.
ORCID
Liang Cheng: 0000-0001-7427-2939
Author Contributions
§X.-D.L. and Y.-T.G. contributed equally to this work.
D
DOI: 10.1021/acs.orglett.9b02183
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Jadhav, A.; Zhuang, Z.-H.; Maloney, D. J. Synthesis and Structure-
Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine
Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with
Anticancer Activity against Nonsmall Cell Lung Cancer. J. Med. Chem.
2014, 57, 8099. (e) Shrestha, L.; Patel, H. J.; Kang, Y.-L.; Sharma, S.;
Chiosis, G.; Taldone, T. Copper mediated coupling of 2-(piperazine)-
pyrimidine iodides with aryl thiols using Cu(I)thiophene-2-carbox-
ylate. Tetrahedron Lett. 2017, 58, 4525. (f) Borjesson, K.; Preus, S.; El-
Sagheer, A. H.; Brown, T.; Albinsson, B.; Wilhelmsson, L. M. Nucleic
Acid Base Analog FRET-Pair Facilitating Detailed Structural
Measurements in Nucleic Acid Containing Systems. J. Am. Chem.
Soc. 2009, 131, 4288. (g) Burns, D. D.; Teppang, K. L.; Lee, R. W.;
Lokensgard, M. E. Fluorescence Turn-On Sensing of DNA Duplex
Formation by a Tricyclic Cytidine Analogue. J. Am. Chem. Soc. 2017,
139, 1372. (h) Lee, J. Y.; Lee, P. H. Palladium-Catalyzed Carbon-
Sulfur Cross-Coupling Reactions with Indium Tri(organothiolate)
and Its Application to Sequential One-Pot Processes. J. Org. Chem.
2008, 73, 7413. (i) Zeng, Y.; Cao, H.-C.; Wang, Y.-S. Facile
Photocyclization Chemistry of 5-Phenylthio-2’-deoxyuridine in
Duplex DNA. Org. Lett. 2006, 8, 2527.
5028. (f) Xie, L.-J.; Wang, R.-L.; Wang, D.; Liu, L.; Cheng, L. Visible-
Light-Mediated Oxidative Demethylation of N6-Methyl Adenines.
Chem. Commun. 2017, 53, 10734.
(14) Norris, P.; Shechter, H. Development of Reactions of 6- and 5-
Substituted 1,3-Dimethyluracils with Dimethylsulfoxonium Methyl-
ide. J. Org. Chem. 1999, 64, 7290.
(15) (a) Aycock, D. F.; Jurch, G. R. Synthesis of alkyl
trithioperesters (alkyl thiocarbonyl disulfides). J. Org. Chem. 1979,
44, 569. (b) Barnes, N. A.; Godfrey, S. M.; Hughes, J.; Khan, R. Z.;
Mushtaq, I.; Ollerenshaw, R. T. A.; Pritchard, R. G.; Sarwar, S. The
reactions of para-halo diaryl diselenides with halogens. A structural
investigation of the CT compound (p-FC6H4)2Se2I2, and the first
reported “RSeI3” compound, (p-ClC6H4)SeI·I2, which contains a
covalent Se−I bond. Dalton Trans 2013, 42, 2735.
(16) Lee, C. H.; Kim, Y. H. Direct regioselective arylsulfenylation
and arylselenenylation at 5-position of uracils mediated by silver
reagents. Tetrahedron Lett. 1991, 32, 2401.
(17) Bradshaw, T. K.; Hutchinson, D. W. 5-Substituted pyrimidine
nucleosides and nucleotides. Chem. Soc. Rev. 1977, 6, 43.
(7) (a) Bergstrom, D.; Beal, P.; Husain, A.; Lind, R.; Jenson, J.
Palladium-mediated coupling between organic disulfides and nucleic
acid constituents. J. Am. Chem. Soc. 1989, 111, 374. (b) Bergstrom,
D.; Beal, P.; Jenson, J.; Lin, X.-P. Palladium-mediated synthesis of C-5
pyrimidine nucleoside thioethers from disulfides and mercurinucleo-
sides. J. Org. Chem. 1991, 56, 5598.
(8) Kopp, F.; Knochel, P. Functionalization of Unprotected Uracil
Derivatives Using the Halogen-Magnesium Exchange. Org. Lett. 2007,
9, 1639.
(9) Jana, A.; Panday, A. K.; Mishra, R.; Parvin, T.; Choudhury, L. H.
Synthesis of Thio and Selenoethers of Cyclic β-Hydroxy Carbonyls
and Amino Uracils: A Metal-Free Regioselective I2/DMSO Mediated
Reaction. ChemistrySelect 2017, 2, 9420.
(10) (a) Lee, D. H.; Kim, Y. H. Regioselective Phenylselenenylation
at the 5-Position of Pyrimidine Nucleosides Mediated by Manganese-
(III) Acetate. Synlett 1995, 1995, 349. (b) Anzai, K. Alkyl- and
arylthiation of uracil and indole. J. Heterocycl. Chem. 1979, 16, 567.
(11) (a) Anzai, K. Alkyl- and arylthiation of uracil and indole. J.
Heterocycl. Chem. 1979, 16, 567. (b) Anzai, K. Synthesis of 5-
(methylthio)-, 5-(methanesulfinyl)-, and 5-(methanesulfonyl)uracil
and reaction of the methyl hypobromite adduct of 5-bromouracil with
carbonylmethylene compounds. J. Org. Chem. 1979, 44, 1737.
(c) Zdrowowicz, M.; Chomicz, L.; Zyndul, M.; Wityk, P.; Rak, J.;
Wiegand, T. J.; Hanson, C. G.; Adhikary, A.; Sevilla, M. D. 5-
Thiocyanato-2’-deoxyuridine as a possible radiosensitizer: electron-
induced formation of uracil-C5-thiyl radical and its dimerization. Phys.
Chem. Chem. Phys. 2015, 17, 16907. (d) Peach, M. E. Sulfur Lett.
1986, 5, 23.
(12) Hae Kim, Y.; Rok Roh, K.; Kyung Chang, H. Efficient
Phenylsulfenylation and Phenylselenenylation at the 5-Position of
Uracil Nucleosides with Disulfide and Diselenide Mediated by
[Bis(trifluoroacetoxy)-iodo]benzene. Heterocycles 1998, 48, 437.
(13) (a) Gao, Y.-T.; Jin, X.-Y.; Liu, Q.; Liu, A.-D.; Cheng, L.; Wang,
D.; Liu, L. Iodide/H2O2 Catalyzed Intramolecular Oxidative
Amination for the Synthesis of 3,2’-Pyrrolidinyl Spirooxindoles.
Molecules 2018, 23, 2265. (b) Wei, F.; Cheng, L.; Huang, H.-Y.;
Liu, J.-J.; Wang, D.; Liu, L. Intermolecular Dearomative Oxidative
Coupling of Indoles with Ketones and Sulfonylhydrazines Catalyzed
by I2 for the Synthesis of [2,3]-Fused Indoline Tetrahydropyridazines.
Sci. China: Chem. 2016, 59, 1311. (c) Huang, H.-Y.; Wu, H.-R.; Wei,
F.; Wang, D.; Liu, L. Iodine-Catalyzed Direct Olefination of 2-
Oxindoles and Alkenes via Cross-Dehydrogenative Coupling (CDC)
in Air. Org. Lett. 2015, 17, 3702. (d) Jin, X.-Y.; Wang, R.-L.; Xie, L.-J.;
Kong, D.-L.; Liu, L.; Cheng, L. A chemical Photo-oxidation of 5-
Methyl Cytidines. Adv. Synth. Catal. 2019, DOI: 10.1002/
adsc.201900811. (e) Xie, L.-J.; Yang, X.-T.; Wang, R.-L.; Cheng,
H.-P.; Li, Z.-Y.; Liu, L.; Mao, L. Q.; Wang, M.; Cheng, L.
Identification of Flavin Mononucleotide as Cell-Active Artificial N6-
Methyladenosine RNA Demethylase. Angew. Chem., Int. Ed. 2019, 58,
E
DOI: 10.1021/acs.orglett.9b02183
Org. Lett. XXXX, XXX, XXX−XXX