Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

Article abstract of DOI:10.3762/bjoc.15.72

A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the macrolactamization of the resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diversity of synthetic or natural biaryl bicyclic peptides.

Full text of DOI:10.3762/bjoc.15.72

Solid-phase synthesis of biaryl bicyclic peptides containing a
3-aryltyrosine or a 4-arylphenylalanine moiety
Iteng Ng-Choi, Àngel Oliveras, Lidia Feliu*§ and Marta Planas*¶
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 761–768.
LIPPSO, Departament de Química, University of Girona, Maria
Aurèlia Capmany 69, Girona 17003, Spain
doi:10.3762/bjoc.15.72
Received: 15 January 2019
Accepted: 09 March 2019
Published: 22 March 2019
Email:
Lidia Feliu* - lidia.feliu@udg.edu; Marta Planas* -
marta.planas@udg.edu
Associate Editor: N. Sewald
* Corresponding author
§ Tel.: +34-972418959
¶ Tel.: +34-972418274
© 2019 Ng-Choi et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
borylation; cross-coupling; cyclization; macrocycles; solid-phase
synthesis
Abstract
A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr motif has
been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the
corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the
macrolactamization of the resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic
peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diver-
sity of synthetic or natural biaryl bicyclic peptides.
Introduction
Monocyclic and bicyclic peptides are acquiring a relevant and the cyclization involving the side chain of two amino acids.
interest in current drug discovery. They display improved bio- The latter is considered more convenient, because it does not
logical properties over their acyclic counterparts and, at the interfere on hydrogen bonding between the N- and C-terminal
same time, they are suitable to modulate protein–protein inter- groups of the peptide and their putative target. This method has
actions [1-9]. These advantageous attributes rise from the been used for the macrocyclization of peptides through, for ex-
rigidity of their conformational structure and from the low ample, copper-catalyzed azide–alkyne cycloadditions [14], ring-
susceptibility to protease degradation of the cyclic backbone. closing olefin metathesis [13] or the formation of an aryl–aryl
bond between the side chain of two aromatic amino acids [11].
There is a wide range of methods for the macrocyclization of
linear peptides [1,2,10-14]. The most frequently used are the Cyclic peptides containing biaryl linkages constitute attractive
formation of an amide bond between the N- and the C-terminus targets. On the one hand, a wide range of biaryl natural prod-
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ucts have been reported to display interesting biological proper- solid-supported chemistry, such as the avoidance of tedious
ties, such as biphenomycins, arylomycins and glycopeptide work-up procedures, and the facile elimination by filtration of
antibiotics [4]. On the other hand, the cyclization of linear reagents and byproducts generated during the reactions. There-
peptides through aryl–aryl bond formation confers a relative fore, this work would constitute the first synthetic approach on
conformational constraint on the peptide scaffold. Moreover, solid support of biaryl bicyclic peptides. Moreover, it would
the resulting biaryl motif is able to participate in π–π interac- allow the access to a wide variety of sequences in a flexible
tions with aromatic and hydrophobic residues, and also in manner.
π-cation interactions with positively charged groups. Due to
these structural properties, biaryl cyclic peptides have a great To set up our strategy the biaryl bicyclic octapeptides 1–3 were
potential to meet the ever-increasing expectations of new drugs. chosen as model substrates (Figure 1). They contain commer-
However, their synthesis is viewed as very challenging.
cially available L-amino acids and a different biaryl bond, in
particular, a Phe-Phe, a Phe-Tyr or a Tyr-Tyr linkage.
The formation of biaryl bonds in peptides has been performed
through a Suzuki–Miyaura cross-coupling reaction [15-19] or
Results and Discussion
via a Pd-catalyzed C–H activation reaction [20,21]. We have Synthesis of the biaryl bicyclic peptide 1
used the former reaction for the solid-phase preparation of We first planned the synthesis of the biaryl bicyclic peptide 1
biaryl cyclic peptides bearing a Phe-Phe, a Phe-Tyr or a Tyr- incorporating a Phe-Phe linkage based on the retrosynthetic
Tyr linkage [22,23]. Our approach involved the synthesis of the analysis depicted in Scheme 1. According to this analysis, the
linear peptidyl resin precursor containing the required boronate key steps are the macrolactamization and the intramolecular
and halogenated amino acid derivatives followed by its cycliza- Suzuki–Miyaura cross coupling. Another crucial issue is the
tion through the formation of an aryl–aryl bond between these selection of the anchoring point to the solid support. The gluta-
two amino acids via a Suzuky–Miyaura reaction. It is worth- mine residue placed at the southern hemisphere of 1 was chosen
while to mention that both the borylation and the cross-cou- for this purpose. Thus, the synthesis of 1 would involve the
pling steps were performed on the solid support.
preparation of the linear peptidyl resin 4 bearing a 4-iodo- and a
4-boronophenylalanine residue. The latter would be incorporat-
In this context, herein our aim was to extend our expertise in the ed at the N-terminus of the peptide sequence which would avoid
formation of biaryl linkages to the solid-phase synthesis of the decomposition of the boronic ester during the coupling steps
biaryl bicyclic peptides. To the best of our knowledge, there is [26]. The intramolecular Suzuki–Miyaura cross coupling of 4
only one example on the preparation of this type of compounds followed by macrolactamization of the resulting biaryl mono-
on solid support, even though the final cyclization was per- cyclic peptidyl resin 5 would afford 1.
formed in solution [24,25]. In contrast, in the present study we
envisaged a synthetic strategy for the preparation of biaryl Based on the above, the protected linear peptidyl resin Boc-
bicyclic peptides in which all the steps would be carried out on Phe(4-BPin)-Ala-Gln(Tmob)-Leu-Gln(Tmob)-Phe(4-I)-βAla-
solid phase. It would benefit from the advantages intrinsic to the Glu(Rink-MBHA)-OpNB (4, pNB is p-nitrobenzyl) was assem-
Figure 1: Structure of biaryl bicyclic peptides 1–3.
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Beilstein J. Org. Chem. 2019, 15, 761–768.
Scheme 1: Retrosynthetic analysis for the biaryl bicyclic peptide 1.
bled starting from an Fmoc-Rink-MBHA resin using the stan- biaryl cyclic peptides [22], 4 was treated with Pd2(dba)3
dard 9-fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (t-Bu) (0.2 equiv), P(o-tolyl)3 (0.4 equiv) and KF (4 equiv) in
strategy (Scheme 2). The non-commercially available amino degassed 1,2-dimethoxyethane (DME)/EtOH/H2O (9:9:2) under
acids Boc-Phe(4-BPin)-OH, Fmoc-Phe(4-I)-OH and Fmoc-Glu- microwave irradiation at 120 °C for 30 min (Scheme 2). An
OpNB were prepared in solution. Boc-Phe(4-BPin)-OH was ob- aliquot of the resulting resin 5 was cleaved, and HPLC and
tained from Boc-Phe(4-I)-OH [27] through esterification, mass spectrometry analysis of the crude reaction mixture
Miyaura borylation and hydrolysis of the ester. Fmoc-Phe(4-I)- revealed the formation of the biaryl cyclic peptide 6 in 18%
OH was prepared by treating H-Phe(4-I)-OH [27] with Fmoc- purity. Mass spectrometry analysis showed that the pNB
OSu in dioxane. Fmoc-Glu-OpNB was synthesized from Fmoc- group was removed under the Suzuki–Miyaura reaction condi-
Glu(Ot-Bu)-OH through pNB ester formation and subsequent tions.
removal of the t-Bu group [28,29]. The peptide chain was elon-
gated through sequential Fmoc group removal and coupling To obtain the biaryl bicyclic peptide 1, the Boc group of cyclic
steps. The Fmoc group was removed using piperidine/DMF peptidyl resin 5 was then removed under mild conditions using
(3:7). The coupling of amino acids was mediated by N,N’-diiso- trimethylsilyl triflate (TMSOTf) in presence of 2,6-lutidine in
propylcarbodiimide (DIPCDI) and ethyl 2-cyano-2-(hydroxy- CH2Cl2 (Scheme 2) [30]. Subsequent macrolactamization
imino)acetate (Oxyma) in DMF, except for Fmoc-Glu-OpNB was performed using O-(((1-cyano-2-ethoxy-2-oxoethyl-
and Fmoc-Phe(4-I)-OH, which were coupled using 1-[(1-cyano- idene)amino)oxy)trispyrrilidin-1-yl)phosphonium hexafluoro-
2-ethoxy-2-oxoethylidineaminooxy)dimethylamino- phosphate (PyOxim), Oxyma and DIPEA in N-methyl-2-
morpholino]uronium hexafluorophosphate (COMU), Oxyma pyrrolidone (NMP) for 24 h. The resulting resin was acidolyti-
and N,N’-diisopropylethylamine (DIPEA) in DMF overnight. cally cleaved and the crude reaction mixture was analyzed by
After peptide elongation, an aliquot of the resulting resin 4 was HPLC and characterized by mass spectrometry. The latter
treated with trifluoroacetic acid (TFA)/triisopropylsilane (TIS)/ revealed the formation of the expected biaryl bicyclic peptide 1
H2O (95:2.5:2.5) for 2 h affording the linear boronopeptide together with a less intense signal at [M − 18 + H]+, which was
H-Phe(4-B(OH)2)-Ala-Gln-Leu-Gln-Phe(4-I)-βAla-Gln-OpNB attributed to peptide fragmentation during the analysis, as con-
in >99% purity, which was characterized by mass spectrometry. firmed by tandem mass spectrometry.
The boronic acid function resulted from hydrolysis of the
boronic ester during HPLC analysis as shown by mass spec- Synthesis of the biaryl bicyclic peptide 2
trometry.
The synthesis of the biaryl bicyclic peptide 2, which incorpo-
rates a Phe-Tyr linkage, was then investigated (Scheme 3).
With the linear peptidyl resin 4 in hand, we investigated its Similarly to 1, the synthesis of 2 involved the preparation
cyclization by means of an intramolecular Suzuki–Miyaura of the linear peptidyl resin Boc-Tyr(3-B(OH)2,Me)-Ala-
reaction. Thus, based on our previous results on the synthesis of Gln(Tmob)-Gly-Gln(Tmob)-Phe(4-I)-βAla-Glu(Rink-MBHA)-
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Beilstein J. Org. Chem. 2019, 15, 761–768.
Scheme 2: Synthesis of the biaryl bicyclic peptide 1 incorporating a Phe-Phe linkage. Reagents and conditions: (i) Piperidine/DMF (3:7). (ii) Fmoc-
βAla-OH, DIPCDI, Oxyma, DMF. (iii) Fmoc-Phe(4-I)-OH, COMU, Oxyma, DIPEA, DMF, overnight. (iv) Fmoc-Gln(Tmob)-OH, DIPCDI, Oxyma, DMF.
(v) Fmoc-Leu-OH, DIPCDI, Oxyma, DMF. (vi) Fmoc-Ala-OH, DIPCDI, Oxyma, DMF. (vii) Boc-Phe(4-BPin)-OH, DIPCDI, Oxyma, DMF, 3 h.
(viii) Pd2(dba)3, P(o-tolyl)3, KF, DME/EtOH/H2O (9:9:2), MW, 120 °C, 30 min. (ix) TFA/H2O/TIS (95:2.5:2.5), 2 h. (x) TMSOTf, 2,6-lutidine, CH2Cl2.
(xi) PyOxim, Oxyma, DIPEA, NMP, 24 h.
OpNB (7), followed by microwave-assisted intramolecular [31], followed by hydrolysis of the pinacolate and saponifica-
Suzuki–Miyaura reaction, Boc group removal, and final macro- tion of the methyl ester. Boc-Tyr(3-B(OH)2,Me)-OH was
lactamization. Boc-Tyr(3-B(OH)2,Me)-OH was prepared in coupled using DIPCDI and Oxyma in DMF for 3 h. An aliquot
solution through Miyaura borylation of Boc-Tyr(3-I,Me)-OMe of the linear resin 7 was cleaved to provide H-Tyr(3-
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Beilstein J. Org. Chem. 2019, 15, 761–768.
Scheme 3: Synthesis of the biaryl bicyclic peptide 2 incorporating a Phe-Tyr linkage. Reagents and conditions: (i) Piperidine/DMF (3:7). (ii) Fmoc-
βAla-OH, DIPCDI, Oxyma, DMF. (iii) Fmoc-Phe(4-I)-OH, COMU, Oxyma, DIPEA, DMF, overnight. (iv) Fmoc-Gln(Tmob)-OH, DIPCDI, Oxyma, DMF.
(v) Fmoc-Gly-OH, DIPCDI, Oxyma, DMF. (vi) Fmoc-Ala-OH, DIPCDI, Oxyma, DMF. (vii) Boc-Tyr(3-B(OH)2,Me)-OH, DIPCDI, Oxyma, DMF, 3 h.
(viii) Pd2(dba)3, SPhos, KF, DME/EtOH/H2O (9:9:2), MW, 120 °C, 30 min. (ix) TFA/H2O/TIS (95:2.5:2.5), 2 h. (x) TMSOTf, 2,6-lutidine, CH2Cl2.
(xi) PyOxim, Oxyma, DIPEA, NMP, 24 h.
B(OH)2,Me)-Ala-Gln-Gly-Gln-Phe(4-I)-βAla-Gln-OpNB in spectrometry analysis of the crude reaction mixture from the
57% purity, which was characterized by mass spectrometry. cleavage of an aliquot of the resulting resin 8 revealed the for-
Resin 7 was then subjected to an intramolecular mation of the expected biaryl monocyclic peptide 9 (36%
Suzuki–Miyaura reaction using Pd2(dba)3 (0.2 equiv), SPhos purity) together with the oxidized and dehalogenated byproduct
(0.4 equiv) and KF (4 equiv) in degassed DME/EtOH/H2O H-Tyr(3-OH,Me)-Ala-Gln-Gly-Gln-Phe-βAla-Gln-OH, which
(9:9:2) under microwave irradiation at 120 ºC for 30 min. Mass is usually formed in Suzuki–Miyaura reactions [32]. Finally,
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Beilstein J. Org. Chem. 2019, 15, 761–768.
resin 8 was subjected to Boc removal, macrolactamization and Synthesis of the biaryl bicyclic peptide 3
acidolytic cleavage. Mass spectrometry analysis of the crude Similarly to 1 and 2, the biaryl bicyclic peptide 3 bearing a
reaction mixture showed a signal at m/z corresponding to Tyr-Tyr linkage was obtained from the linear peptidyl resin
[M – 18 + H]+, which resulted from the fragmentation of the Boc-Tyr(3-B(OH)2,Me)-Ala-Gln(Tmob)-Leu-Gln(Tmob)-
biaryl bicyclic peptide 2 during mass spectrometry analysis.
Tyr(3-I,Me)-βAla-Glu(Rink-MBHA)-OpNB (10) (Scheme 4).
Scheme 4: Synthesis of the biaryl bicyclic peptide 3 incorporating a Tyr-Tyr linkage. Reagents and conditions: (i) Piperidine/DMF (3:7). (ii) Fmoc-
βAla-OH, DIPCDI, Oxyma, DMF. (iii) Fmoc-Tyr(3-I,Me)-OH, COMU, Oxyma, DIPEA, DMF, overnight. (iv) Fmoc-Gln(Tmob)-OH, DIPCDI, Oxyma,
DMF. (v) Fmoc-Leu-OH, DIPCDI, Oxyma, DMF. (vi) Fmoc-Ala-OH, DIPCDI, Oxyma, DMF. (vii) Boc-Tyr(3-B(OH)2,Me)-OH, DIPCDI, Oxyma, DMF,
3 h. (viii) Pd2(dba)3, SPhos, KF, DME/EtOH/H2O (9:9:2), MW, 120 °C, 30 min. (ix) TFA/H2O/TIS (95:2.5:2.5), 2 h. (x) TMSOTf, 2,6-lutidine, CH2Cl2.
(xi) PyOxim, Oxyma, DIPEA, NMP, 24 h.
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Beilstein J. Org. Chem. 2019, 15, 761–768.
ORCID® iDs
Fmoc-Tyr(3-I,Me)-OH was prepared in solution from
Boc-Tyr(3-I,Me)-OMe [31] through Boc group removal
followed by methyl ester hydrolysis and Fmoc protection
of the Nα-amino group. Fmoc-Tyr(3-I,Me)-OH was coupled
using COMU, Oxyma and DIPEA in DMF overnight. An
aliquot of resin 10 was cleaved providing the expected
linear peptide in 98% purity. Microwave-assisted intra-
molecular Suzuki–Miyaura reaction of 10 was carried out
using the same conditions for the macrocyclization of
resin 7. Mass spectrometry analysis of the crude reaction
mixture from cleavage of an aliquot of the resulting 11 revealed
the formation of the expected biaryl cyclic peptide 12 in
21% HPLC purity. Selective Boc group removal, macrolac-
tamization and final cleavage yielded the biaryl bicyclic peptide
3. Mass spectra showed a signal at [M + H]+ together with a
major one at [M − 18 + H]+ attributed to the fragmentation
of 3 during the analysis, as confirmed by tandem mass spec-
trometry.
Lidia Feliu - https://orcid.org/0000-0001-9792-6106
Marta Planas - https://orcid.org/0000-0003-4988-4970
References
1. Martí-Centelles, V.; Pandey, M. D.; Burguete, M. I.; Luis, S. V.
Chem. Rev. 2015, 115, 8736–8834. doi:10.1021/acs.chemrev.5b00056
2. Marsault, E.; Peterson, M. L. J. Med. Chem. 2011, 54, 1961–2004.
doi:10.1021/jm1012374
3. Yudin, A. K. Chem. Sci. 2015, 6, 30–49. doi:10.1039/c4sc03089c
4. Feliu, L.; Planas, M. Int. J. Pept. Res. Ther. 2005, 11, 53–97.
doi:10.1007/s10989-004-1723-1
5. Rhodes, C. A.; Pei, D. Chem. – Eur. J. 2017, 23, 12690–12703.
doi:10.1002/chem.201702117
6. Watson, G. M.; Kulkarni, K.; Sang, J.; Ma, X.; Gunzburg, M. J.;
Perlmutter, P.; Wilce, M. C. J.; Wilce, J. A. J. Med. Chem. 2017, 60,
9349–9359. doi:10.1021/acs.jmedchem.7b01320
7. Teufel, D. P.; Bennett, G.; Harrison, H.; van Rietschoten, K.; Pavan, S.;
Stace, C.; Le Floch, F.; Van Bergen, T.; Vermassen, E.; Barbeaux, P.;
Hu, T.-T.; Feyen, J. H. M.; Vanhove, M. J. Med. Chem. 2018, 61,
2823–2836. doi:10.1021/acs.jmedchem.7b01625
8. Lian, W.; Jiang, B.; Qian, Z.; Pei, D. J. Am. Chem. Soc. 2014, 136,
9830–9833. doi:10.1021/ja503710n
Conclusion
A methodology for the solid-phase synthesis of biaryl bicyclic
peptides bearing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr linkage is
described. The synthesis includes the preparation of a biaryl
monocyclic peptidyl resin through an intramolecular micro-
wave-assisted Suzuki–Miyaura cross coupling which is fol-
lowed by a final macrolactamization step. This work consti-
tutes the first solid-phase synthetic approach to biaryl bicyclic
peptides. The method described is general and allows access to
a diversity of novel Phe- and Tyr-containing biaryl bicyclic
peptides.
9. Bartoloni, M.; Jin, X.; Marcaida, M. J.; Banha, J.; Dibonaventura, I.;
Bongoni, S.; Bartho, K.; Gräbner, O.; Sefkow, M.; Darbre, T.;
Reymond, J.-L. Chem. Sci. 2015, 6, 5473–5490.
doi:10.1039/c5sc01699a
10.White, C. J.; Yudin, A. K. Nat. Chem. 2011, 3, 509–524.
doi:10.1038/nchem.1062
11.Willemse, T.; Schepens, W.; van Vlijmen, H. W. T.; Maes, B. U. W.;
Ballet, S. Catalysts 2017, 7, 74. doi:10.3390/catal7030074
12.Lau, Y. H.; de Andrade, P.; Wu, Y.; Spring, D. R. Chem. Soc. Rev.
2015, 44, 91–102. doi:10.1039/c4cs00246f
13.Gleeson, E. C.; Jackson, W. R.; Robinson, A. J. Tetrahedron Lett.
2016, 57, 4325–4333. doi:10.1016/j.tetlet.2016.08.032
14.Ahmad Fuaad, A. A. H.; Azmi, F.; Skwarczynski, M.; Toth, I. Molecules
2013, 18, 13148–13174. doi:10.3390/molecules181113148
15.Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
doi:10.1021/cr00039a007
Supporting Information
Supporting Information File 1
Experimental, synthesis, and characterization of all the
compounds.
16.Suzuki, A. Angew. Chem., Int. Ed. 2011, 50, 6722–6737.
doi:10.1002/anie.201101379
17.Bois-Choussy, M.; Cristau, P.; Zhu, J. Angew. Chem., Int. Ed. 2003,
42, 4238–4241. doi:10.1002/anie.200351996
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-72-S1.pdf]
18.Carbonnelle, A.-C.; Zhu, J. Org. Lett. 2000, 2, 3477–3480.
doi:10.1021/ol006520g
19.Yoburn, J. C.; Van Vranken, D. L. Org. Lett. 2003, 5, 2817–2820.
doi:10.1021/ol034801t
Acknowledgements
20.Mendive-Tapia, L.; Preciado, S.; García, J.; Ramón, R.; Kielland, N.;
Albericio, F.; Lavilla, R. Nat. Commun. 2015, 6, 7160.
doi:10.1038/ncomms8160
Parts of this manuscript are adapted from the Ph. D. disserta-
tion of Iteng Ng-Choi, Universitat de Girona, 2015: Solid-Phase
Synthesis of 5-Arylhistidine-Containing Peptides: from Linear
Antimicrobial Peptides to Cyclic Peptides Derived from
Arylomycins and Aciculitins. The authors acknowledge the
Serveis Tècnics de Recerca of the University of Girona for the
MS analysis. This work was supported by the Ministerio de
Economía y Competitividad (MINECO) [grant numbers
AGL2009-13255-C02-02/AGR, AGL2012-39880-C02-02 and
AGL2015-69876-C2-2-R].
21.Mendive-Tapia, L.; Bertran, A.; García, J.; Acosta, G.; Albericio, F.;
Lavilla, R. Chem. – Eur. J. 2016, 22, 13114–13119.
doi:10.1002/chem.201601832
22.Afonso, A.; Feliu, L.; Planas, M. Tetrahedron 2011, 67, 2238–2245.
doi:10.1016/j.tet.2011.01.084
23.Afonso, A.; Cussó, O.; Feliu, L.; Planas, M. Eur. J. Org. Chem. 2012,
6204–6211. doi:10.1002/ejoc.201200832
24.García-Pindado, J.; Royo, S.; Teixidó, M.; Giralt, E. J. Pept. Sci. 2017,
23, 294–302. doi:10.1002/psc.2993
767

Beilstein J. Org. Chem. 2019, 15, 761–768.
25.García-Pindado, J.; Willemse, T.; Goss, R.; Maes, B. U. W.; Giralt, E.;
Ballet, S.; Teixidó, M. Biopolymers 2018, 109, e23112.
doi:10.1002/bip.23112
26.Afonso, A.; Rosés, C.; Planas, M.; Feliu, L. Eur. J. Org. Chem. 2010,
1461–1468. doi:10.1002/ejoc.200901350
27.Lei, H.; Stoakes, M. S.; Herath, K. P. B.; Lee, J.; Schwabacher, A. W.
J. Org. Chem. 1994, 59, 4206–4210. doi:10.1021/jo00094a036
28.Isidro-Llobet, A.; Álvarez, M.; Albericio, F. Tetrahedron Lett. 2005, 46,
7733–7736. doi:10.1016/j.tetlet.2005.09.043
29.Isidro-Llobet, A.; Guasch-Camell, J.; Álvarez, M.; Albericio, F.
Eur. J. Org. Chem. 2005, 3031–3039. doi:10.1002/ejoc.200500167
30.Zhang, A. J.; Russell, D. H.; Zhu, J.; Burgess, K. Tetrahedron Lett.
1998, 39, 7439–7442. doi:10.1016/s0040-4039(98)01631-1
31.Cerezo, V.; Amblard, M.; Martinez, J.; Verdié, P.; Planas, M.; Feliu, L.
Tetrahedron 2008, 64, 10538–10545. doi:10.1016/j.tet.2008.08.077
32.Lennox, A. J. J.; Lloyd-Jones, G. C. Chem. Soc. Rev. 2014, 43,
412–443. doi:10.1039/c3cs60197h
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