A Photolabile Carboxyl Protecting Group for Solid Phase Peptide Synthesis

Article abstract of DOI:10.1002/open.202000324

A new kind of photolabile protecting group (PLPG) for carboxyl moieties was designed and synthesized as the linker between resin and peptide. This group can be used for the protection of amino acid carboxyl groups. The peptide was synthesized on Nph (2-hy

Full text of DOI:10.1002/open.202000324

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A Photolabile Carboxyl Protecting Group for Solid Phase
Peptide Synthesis
Hongpeng Yang,[a, b] Tao Peng,[b] Xiaoxue Wen,[b] Tingting Chen,[b] Yunbo Sun,[b]
Shuchen Liu,[b] Gang Wang,*[b] Shouguo Zhang,*[b] and Lin Wang*[a, b]
A new kind of photolabile protecting group (PLPG) for carboxyl
moieties was designed and synthesized as the linker between
resin and peptide. This group can be used for the protection of
amino acid carboxyl groups. The peptide was synthesized on
Nph (2-hydroxy-3-(2-nitrophenyl)-heptanoic acid)-derivatized
resins and could be cleaved under UV exposure, thus avoiding
the necessity for harsh acid-mediated resin cleavage. The PLPG
has been successfully used for solid-phase synthesis of
peptides.
1. Introduction
nitro group.[8] In our early work,[9] 2-(2-nitrophenyl)propan1-ol
(NppÀ OH) (Figure 1) was successfully synthesized as a PLPG. It
can protect the carboxylic acid group of amino acids and be
quickly removed[10] after UV irradiation for 30 minutes. However,
there are still some disadvantages to this protecting group. Its
primary alcohol is unstable after being treated with strong
nucleophilic reagents, and it can have easy concurrent side
reactions with diketopiperazine. Thus, for the first time, we
designed and synthesized a novel carboxyl PLPG (Nph) (Fig-
ure 1) that can be applied in peptide solid-phase synthesis as a
linker between resin and amino acid. It was used as the linker
between the resin and the amino acid by protecting the
carboxyl group of the amino acid versus NppÀ OH. The linker is
stable in alkaline conditions and can also avoid the occurrence
of diketopiperazine reaction and be quickly removed with
light.[6,7,8,9,10]
Protecting groups are indispensable tools in organic
chemistry.[1] Photochemical reactions are very appealing from
both an economical and environmental perspective. Indeed,
light is a very cheap reagent, and it does not generate chemical
waste.[2] Photochemical methods are valuable alternatives to
conventional approaches that often employ acids, bases, or
reducing/oxidizing reagents.[3]
Photolabile protecting groups (PLPGs) are protecting groups
that can produce free radicals or isomerize molecules under
light of a certain wavelength. They can concurrently release
target molecules.[4] Compared to traditional protecting groups,
PLPGs avoid the use of strong acid[5] and strong bases
condition. They can release the protecting substrate only under
irradiation at a specific wavelength.
The past two decades have witnessed the continuous
emergence of new PLPGs and their creative applications, such
as o-nitrobenzyl groups, coumarin groups, arylcarbonylmethyl 2. Results and Discussion
groups, and arylmethyl groups.[6] The 2-nitrobenzyl derivatives
are the most commonly used PLPG.[7] The photochemical
cleavage mechanism of the (o-nitrobenzyl)oxy function is
triggered by the abstraction of a benzylic H-atom by the excited
Here, 2-fluoronitrobenzene was the starting material, and ethyl
acetoacetate was the substitute in DMSO (dimethyl sulfoxide); 2
°
was obtained after heating in 80 C. The initial strategy for
synthesis of 4 was to get 3 by inserting the side chain ethyl
bromobutyrate directly to 2, and 3 was then decarboxylated to
obtain 4 to avoid the double substituted side chain products.
However, the subsequent decarboxylation of 3 did not occur.
Therefore, in the alternative strategy, 2 was decarboxylated to
3’, and then the side chain was inserted to get 4.[11]
Intermediate 5 was obtained via reduction of 4 with sodium
borohydride in an ice bath in methanol. Finally, target product
[a] H. Yang, Prof. L. Wang
Faculty of Environment & Life
Beijing University of Technology
Beijing 100124 (China)
E-mail: 18211168112@163.com
[b] H. Yang, Prof. T. Peng, Prof. X. Wen, T. Chen, Prof. Y. Sun, Prof. S. Liu,
G. Wang, Prof. S. Zhang, Prof. L. Wang
Beijing Institute of Radiation Medicine
27 Taiping Road, Haidian District
Beijing 100850 (China)
E-mail: wanglin@bmi.ac.cn
zhangshouguo1409@sina.com
wgang85@126.com
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/open.202000324
© 2021 The Authors. Published by Wiley-VCH GmbH. This is an open access
article under the terms of the Creative Commons Attribution Non-Com-
mercial NoDerivs License, which permits use and distribution in any med-
ium, provided the original work is properly cited, the use is non-commercial
and no modifications or adaptations are made.
Figure 1. Structure of NppÀ OH and Nph.
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Scheme 1. Synthesis of Nph.
Scheme 2. Synthesis of fully protected CP-9 and deprotected CP-9 with Nph.
Nph (6) was obtained from 5 after hydrolysis and acidification.
sis of CP-9 is very important, and we have studied its synthesis
in which the amino acids of CP-9 were loaded with Nph as the
PLPG.[12]
Their structures were verified by NMR/MS (Scheme 1).[11]
A
series of tests involving amino acid loading rate,
photolysis time, photolysis efficiency, acid, and alkali resistance
on Nph were performed to prove that it could protect the
carboxyl group for peptide chain assembly as the linker of
amino acid and aminomethyl resin. This step involved the anti-
radiation peptide CBLB612 (CP-9) (Figure 2) with Nph.
Nph was connected to amino resin (7) with HCTU (N,N,N’,N’-
tetramethyl-O- (6-chloro-1H-benzotriazol-1-yl) uraniumhexa-
fluorophosphate) and NMM (4-methylmorpholine) in DMF.
When connected completely, the amino acid lysine was loaded
in DCM-DMAP (4-(N,N-dimethylamino) pyridine) condition to
obtain 9. The loading of other amino acids followed the method
of solid-phase synthesis to get 10, which was photolyzed to
obtain fully protected CP-9. This was then deprotected and
then photolyzed to obtain deprotected CP-9 (Scheme 2). In the
synthesis of CP-9, the loading ratios of amino acids were tested.
The general procedure was that the resin with one amino acid
was washed, dried, and weighed. The loading ratio was
calculated as follows: loading ratio (%)=(M2-m)/M1*100% (M2:
total weight of resin and amino acid, m: weight of resin, M1:
theoretical weight gain of amino acids). The loading ratios of
CBLB612 is an anti-radiation peptide with the peptide chain
Val-Gln-Gly-Glu-Glu-Ser– Asn-Asp-Lys-OH (CP-9).[12] The synthe-
Figure 2. Structure of CBLB612.
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Table 1. Loading ratio of Nph to amino acid.
Entry
Amino acid
Loading ratio (%)
1
2
3
4
5
6
7
8
Lys
Asp
Asn
Ser
Glu
Gly
Gln
Val
96.5
95.2
97.2
95.3
91.7
94.4
93.2
95.7
Figure 4. HPLC of deprotected CP-9 under different photolysis times.
Figure 3. HPLC of fully protected CP-9 under different photolysis times.
lysine (Lys), aspartic acid (Asp), asparagine (Asn), serine (Ser),
glutamic acid (Glu), glycine (Gly), glutamine (Gln), and valine
(Val) were calculated by the same method (Table 1).
The photolysis efficiency was evaluated by 10. Here, 0.1 g
10 in 5 mL THF was exposed to a 365 nm ultraviolet lamp for 5,
10, 15, or 20 min. A 400 μL of the irradiation solution was
aliquoted and analyzed by HPLC. The eluent was 90% aqueous
acetonitrile. The HPLC results showed that the peak strength of
peptide did not increase any more at 15 min (Figure 3),
indicating that the peptide was almost completely photolyzed
at 15 min.[13] After purification, the purified fully protected CP-9
was obtained.[13]
Figure 5. HPLC of Fmoc-Gly-OH in trifluoroacetic acid for different times.
Scheme 3. Synthesis of Peptide 2 from Peptide 1.
Next, 0.2 g of 10 was put into a 10 mL peptide synthetic
tube, and 20% piperidine-DMF was used to remove the Fmoc
protective group and cleavage solution (1.8 mL trifluoroacetic
acid, 0.1 mL water, and 0.1 mL triisopropylsilane) to remove
other protective groups. After 5 mL THF was added, the
samples (400 μL) were collected after light exposure for 5, 10,
15, 20, 25, or 30 min. The mobile phase was 3% acetonitrile-
water solution. The spectra showed that the peptide content
does not increase further after 25 minutes of light exposure
(Figure 4). Thus, we concluded that the peptide release was
complete after 20 minutes of illumination. The pure product of
deprotected CP-9 was obtained after purification.
Additional experiments verified the stability of the protect-
ing group under acidic and alkaline conditions. Fmoc-Gly-OH
was selected because it had no other protective groups, which
minimized adverse influence on the results. Here, 0.1 g of the
peptide resin was taken into an EP tube with 1 ml TFA. After
standing, 100 μL samples were collected at 2, 4, 6, and 12 h and
then dried with argon and dissolved with 0.5 mL 50%
acetonitrile water solution for liquid phase analysis. The liquid
phase was 50% acetonitrile-water solution. The data of the
peak area showed that the protective group could tolerate 6 h
under acidic conditions (Figure 5).
The side effects of diketopiperazine occur under alkaline
conditions when the first amino acid or the second amino acid
is Gly or Pro. Therefore, the two peptides (Peptide 1 (Gly-Pro-
NHFmoc) and Peptide 2 (Gly-Pro-Lys-NHFmoc) (Scheme 3)) that
meet these conditions were selected as the research objects,
and solid-phase synthesis was performed with Nph as the linker
to investigate the tolerance in alkaline conditions.
Peptide 1 and 2 were successively synthesized, and the
absorbance of Fmoc from their deprotection solution was
measured under UV. These consistent absorbance values
indicated that no diketopiperazine side reaction occurred.
Variable absorbance values indicated that the diketopiperazine
side reaction occurred.
After Peptide 1 was synthesized, 5 mL of 20% piperidine
DMF solution was added into the peptide synthesis vessel for
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deprotection. This was then shaken for 1 h at room temperature
and allowed to stand for for 5 min. Next, 100 μL of deprotection
solution was aspirated to 10 mL, and the absorbance was
measured by UV.
After extruding the deprotection solution, the resin was
cleaned with DMF and loaded with amino acid Lys. After
detection with ninhydrin, the 5 mL of 20% piperidine DMF
solution was added into the peptide synthesis vessel for
deprotection. The resin was shaken at room temperature for 1 h
and then allowed to stand for 5 min. Next, 100 μL of
deprotection solution was absorbed and diluted to 10 mL and
then measured for UV absorbance.
results suggested that the linker has high protection/depro-
tection efficiencies and remarkable stability. Both the protection
and deprotection reactions of Nph can be carried out in a
neutral environment. Furthermore, Nph is tolerant of both acid
and alkali conditions; it can be applied to the solid-phase
synthesis of peptides without other chemical reagents. The
deprotected peptide and whole protected peptide were
connected to the resin by Nph and could be removed rapidly at
365 nm, thus avoiding cutting the peptide and removing other
protective groups under acid conditions. Thus, Nph has broad
application prospects for carboxyl protection in solid-phase
peptide synthesis.[14]
The UV spectra of the two deprotection solutions showed
that the Fmoc absorption values of the two deprotection
solutions were almost the same (Figure 6 Figure 7). This Experimental Section
indicates that the concentrations of Fmoc in the two samples
are the same. This result indicated that there was no side
reaction of diketopiperazine, which proved that Nph had good
tolerance to alkaline environments.
General
All chemicals and solvents were of analytical grade and used
without further purifications. All organic solutions were concen-
trated by rotary evaporation under reduced pressure. Flash column
chromatography was performed with 230–400 mesh silica gel. The
reaction progress was monitored by silica gel thin layer chromatog-
raphy (TLC) plates. UV-visible spectra were obtained using a
Shimadzu UV-2501PC UV-visible Recording spectrophotometer with
a sample concentration of 8.56*10À 5 M. The 1H and 13C NMR spectra
were recorded on a Varian INOVA 600 spectrometer and Bruker 400
NMR spectrometer; chemical shifts are expressed in parts per
million (δ scale) downfield from tetramethylsilane and are refer-
enced to the residual protium in the NMR solvent (DMSO-d6: 2.50).
Data are presented as follows: chemical shift, multiplicity (s=
singlet, d=doublet, t=triplet, q=quartet, m=multiplet and/or
multiple resonances), and integration of coupling constant in hertz
(Hz). Photolysis used a 250 W UV lamp (365 nm).
3. Conclusion
The use of 2-fluoronitrobenzene as a starting material to design
and synthesize PLPG Nph as a linker between the resin and
peptide has been evaluated. It can protect the carboxyl group
of amino acids. The linker was synthesized from commercially
available inexpensive materials with high yield.[14] A loading
ratio experiment used eight amino acids and photolysis. The
1-(2-Nitrophenyl) Propan-2-one (3’)
Ethyl acetoacetate 7.05 g (50.0 mmol) was dissolved in 60 mL
DMSO. Anhydrous potassium carbonate 20.7 g (150.0 mmol) and 2-
fluoronitrobenzene 113.0 g (100.0 mmol) were added and heated
°
at 80 C. The reaction was monitored completely by TLC. After the
reaction, the reaction solution was cooled to room temperature
and poured into ice water. The reaction was neutralized to pH 5–6
with 1 M hydrochloric acid and then extracted with ethyl acetate
(50 mL×3). The organic phase combined and dried with anhydrous
sodium sulfate. It was filtered and concentrated to get crude
product 2, which was directly placed in the next reaction without
purification.
Figure 6. UV absorbance at different Wavelengths of Peptide 1.
Next, 2 was dissolved in 40 mL DMSO with 10 mL saturated sodium
°
chloride solution. The solution was heated at 120 C; 50 mL water
was added to dilute the reaction solution when complete. The
solution was extracted with DCM (30 mL×3) and washed with
saturated brine twice. Drying of the collected organic layer over
Na2SO4 was followed by concentration of the product. Product 3’
was purified by flash chromatography (petroleum ether: ethyl
acetate=10/1). 7.75 g (86.6%); yellow oil Rf=0.2 (petroleum ether/
1
ethyl acetate=6/1); H NMR (400 MHz, DMSO) δ 8.07 (dd, J=8.4,
1.4 Hz, 1H), 7.71 (td, J=7.56, 1.4 Hz, 1 H), 7.55 (td, J=8.4, 1.68 Hz, 1
H), 7.45 (dd, J=7.56, 1.12 Hz, 1 H), 4.24 (s, 2 H), 2.22 (s, 3H). 13C NMR
(100 MHz, DMSO) δ 149.12, 134.26, 134.13, 130.94, 128.92, 125.12,
48.02, 40.59, 40.39, 40.18, 39.97, 39.76, 39.55, 39.34. HRMS (ESI): m/z
calcd for C9H9NO3 +H: 180.06, found 180.0656.
Figure 7. UV absorbance at different Wavelengths of Peptide 2.
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Deprotection: The resin was shaken in 5 mL of 20% piperidine-DMF
solution for 15 min at room temperature and then washed with
DMF three times.
2-Carbonyl-3-(2-Nitrophenyl)-Ethyl Heptanoate (4)
1.8 g (10.0 mmol) 3’ was dissolved in 50 mL of anhydrous
acetonitrile; 11.6 g (85.0 mmol) of anhydrous potassium carbonate
and 15 mg of 18-crown-6 were added to the solution. Ethyl
bromobutyrate in 5.0 mL of acetonitrile was dropped into the
solution slowly and then refluxed. The reaction was monitored
completely by TLC (for about 16 h). When the reaction was
complete, the solvent was evaporated to dryness, and citric acid
water was added and extracted with ethyl acetate (50 mL×3). The
combined organic phase was washed with saturated sodium
chloride solution and dried with the anhydrous sodium sulfate.
Product 4 was purified by flash chromatography (petroleum ether:
ethyl acetate=10/1) 2.45 g (83.6%) yellow oil Rf=0.3 (petroleum
ether/ethyl acetate=10/1) 1H NMR (400 MHz, DMSO) δ 7.97 (dd, J=
8.16, 1.12 Hz, 1 H), 7.73 (td, J=7.56, 1.4 Hz, 1 H), 7.56 (td, J=8.12,
1.4 Hz, 1 H), 7.47 (dd, J=7.6, 1.12 Hz, 1 H), 4.13 (dd, J=9.0, 5.6 Hz, 1
H),4.01 (dd, J=14.32, 7.0 Hz, 2 H), 2.27 (td, J=7.56, 2.52 Hz, 2 H),
2.09 (s, 3H), 2.07–1.99 (m, 1 H), 1.73–1.64 (m, 1 H), 1.46–1.39 (m, 1
H), 1.31–1.28 (m, 1 H), 1.15 (t, J=18.76 Hz, 3 H). 13C NMR (100 MHz,
DMSO) δ 206.35, 172.98, 150.18, 133.86, 132.94, 130.81, 129.01,
124.94, 60.19, 53.52, 40.61, 40.40, 40.19, 39.98, 39.77, 39.56, 39.36,
33.60, 30.26, 29.28, 22.92, 14.54. HRMS (ESI): m/z calcd. for
C15H19NO5 +Na+: 316.13 [M+Na]+, found 316.1153.
Loading with other amino acids: The resin was shaken in the DMF
solution containing Fmoc-AA-OH (0.5 mmol), HCTU (0.5 mmol) and
NMM (0.5 mmol) for 2 h at room temperature. The reaction was
°
monitored by ninhydrin at 100 C for 5 min.
Fully Protected CP-9and Deprotected CP-9from 10
10 (0.1 g) was dissolved into THF (5 mL) and exposed to a 365 nm
ultraviolet lamp for 5, 10, 15, or 20 min; 400 μL of the irradiated
solution was removed and detected by HPLC. The liquid phase was
90% acetonitrile-water solution. After purification, the fully pro-
tected CP-9 was obtained (photolysis rate was 74.6%) and
identified by mass spectrometry. TOF-MS: m/z calculated for
2058.0311[M+Na]+ found 2058.8354.
10 (0.2 g) was added to 20% piperidine-DMF (6 mL) to remove
Fmoc protection and allow cleavage (1.8 mL trifluoroacetic acid,
0.1 mL water and 0.1 mL triisopropylsilane) to remove other
protective groups. The resin after treatment was put into 5 mL THF
and exposed to a 365 nm ultraviolet lamp for 5, 10, 15, 20, or
25 min; 400 μL of the irradiated solution was removed and studied
by HPLC at each time point. The liquid phase was 3% acetonitrile-
water solution. After purification, the deprotected CP-9 was
obtained (photolysis rate was 67.0%) and identified by mass
spectrometry. TOF-MS: m/z calculated for 1005.4411[M+H]+, found
1005.4479.
2-Hydroxy-3-(2-Nitrophenyl)-Heptanoic acid (Nph): Here, 4 was
dissolved in 50 mL of methanol, and 0.38 g of sodium borohydride
were added slowly in an ice bath and stirred. The reaction was
monitored and completed after 30 min, as shown by TLC. The
reaction solution was evaporated to dryness to obtain the crude
product of 5 (2.53 g).
Supporting Information: Further detailed experimental procedures
5 was dissolved in the mixed solvent (5:1) of EtOH and water with
0.4 g NaOH. It was stirred at room temperature for 12 h. The
reaction was monitored completely by TLC. The solvent was then
evaporated when the reaction was complete. The crude product
was washed with hydrochloric acid solution to pH 1 and extracted
with DCM. Drying collected the organic layer over Na2SO4, followed
by concentration. The product Nph was purified by flash
chromatography (dichloromethane/ methanol=25/1) as light yel-
low solid; 1.91 g (85.6%) light yellow solid Rf=0.6 (dichloro-
methane/ methanol=20/1) 1H NMR (400 MHz, DMSO) δ 11.95
(s,1H), 7.68 (dd, J=7.84, 0.84 Hz, 1H), 7.63-7.55 (m, 2 H), 7.38 (td, J=
7.0, 1.68 Hz, 1 H), 4.64 (d, J=3.08 Hz, 1 H), 3.73 (d, J=1.68 Hz, 1 H),
2.87 (dd, J=13.72, 7.0 Hz, 1 H), 2.13 (dd, J=13.16, 6.72 Hz, 2 H),
1.69 (dd, J=15.68, 7.84 Hz, 2H), 1.39-1.28 (m, 1 H), 1.25-1.16 (m, 1
H), 0.89 (d, J=6.44 Hz, 3 H). 13C NMR (100 MHz, DMSO) δ 174.15,
152.53, 136.21, 132.29, 130.02, 127.47, 123.33, 69.21, 46.09, 34.07,
31.22, 23.01, 22.05. HRMS (ESI): m/z calcd. for C13H17NO5-H,
266.11[MÀ H]À , found 266.1034.
1
and copies of H and 13C NMR spectra as well as other chromato-
grams disseminated are available as supporting information.
Acknowledgements
The authors are grateful to the National Natural Science
Foundation of China (Grant No. 81273431, 21102176 and
21272273) for its financial support for this project.
Conflict of Interest
The authors declare no conflict of interest.
The resin loading of fully protected CP-9 (10): The linker (Nph) was
placed on the amino resin: 0.1 mmol (0.217 g) of amino resin in
DCM for swelling for 20 min with Nph (0.5 mmol), HCTU (0.5 mmol),
and NMM (0.5 mmol). These were dissolved in 6 ml DMF and
shaken at room temperature for 2 h. The reaction was monitored
Keywords: linker molecules · peptides · protecting groups ·
photolabile compounds · solid-phase synthesis
°
by ninhydrin at 100 C for 5 min. Loading the first amino acid:
[1] P. Wang, J. Photochem. Photobiol. A 2017, 335, 300–310.
[2] C. G. Bochet, Tetrahedron Lett. 2000, 41, 6341–6346.
[3] T. W. Greene, P. G. M. Wuts, Wiley&Sons, GREENE’S PROTECTIVE GROUPS
IN ORGANIC SYNTHESIS. New York, 2006.
[4] a) C. Ma, Y. Zhang, H. Zhang, J. Li, Y. Nishiyama, H. Tanimoto, T.
Morimoto, K. Kakiuchi, Synlett. 2016: s-0036–1588915; b) M. Lu, O. D.
Fedoryak, B. R. Moister, T. M. Dore, Org. Lett. 2003, 12, 2119–2122.
[5] A. Colombo, D. L. F. Natalia, J. C. Fernàndez, D. Fernández-Forner, F.
Albericio, P. Forns, Org. Lett. 2007, 21, 4319–4322.
Fmoc-Lys-OH (0.5 mmol) and DMAP (0.0122 g, 0.10 mmol) were
dissolved in 5 mL DCM (0.5 mL DMF for solubilization). Diisopro-
pylcarbodiimide (0.06 g, 0.5 mmol) was slowly dropped into the
reaction solution. The solution was shaken at room temperature for
6 h and then fed again.
Sealing: The resin was shaken in 5 mL (1 mL acetic anhydride, 1 mL
pyridine, 3 mL DMF) and mixed for 1 h after washing with DMF
three times at room temperature.
[6] Y. Zhang, H. Zhang, M. Chi, J. Li, K. Kakiuchi, Tetrahedron Lett. 2016, 57,
5179–5184.
[7] M. M. Mahmoodi, D. Abate-Pella, T. J. Pundsack, C. C. Palsuledesai, P. C
Goff, D. A. Blank, M. D. Distefano, J. Am. Chem. Soc. 2016, 138, 5848–
5859.
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[8] H. Morrison, B. H. Migdalof, J. Org. Chem. 2002, 30, 3996.
[9] G. Wang, T. Peng, S. Zhang, J. Wang, X. Wen, H. Yan, L. Hu, L. Wang, RSC
Adv. 2015, 5, 28344–28348.
[13] D. Ramesh, R. Wieboldt, L. Niu, Barry. K. Carpenter, George. P. Hess, Sci.
Ind. 1993, 23, 11074–11078.
[14] P. Wang, H. Hu, Y. Wang, Org. Lett. 2007, 8, 1533–1535.
[10] P. Wang, Y. Wang, H. Hu, C. Spencer, X. Liang, L. Pan, J. Org. Chem.
2008, 16, 6152–6157.
[11] R. A. Bunce, D. M. Herron, L. B. Johnson, S. V. Kotturi, J. Org. Chem. 2001,
8, 2822–2827.
[12] V. K. Singh, E. J. Ducey, D. S. Brown, M. H. Whitnall, Int. J. Radiat. Biol.
2012, 88, 296–310.
Manuscript received: November 9, 2022
Revised manuscript received: February 18, 2021
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