Please do not adjust margins
Page 5 of 6
Organic & Biomolecular Chemistry
Paper
Organic & Biomolecular Chemistry
A)
HCl•H2N-Gly-OMe (1.5 equiv)
EDC•HCl (1.5 equiv)
HOBt (1.5 equiv)
Mehta, Tetrahedron Lett. 2017, 58, 13D5O7–I:11307.1203. 9/C9OB00966C
(a) T. Iizuka, R. Fudou, Y. Jojima, S. Ogawa, S. Yamanaka,
Y. Inukai and M. Ojika, J. Antibiot. 2006, 59, 385–391; (b) L.
Karmann, K. Schulz, J. Herrmann, R. Müller and U.
Kazmaier, Angew. Chem. Int. Ed. 2015, 54, 4502–4507; (c) S.
Kappler, L. Karmann, C. Prudel, J. Herrmann, G. Caddeu, R.
Müller, A. M. Vollmar, S. Zahler and U. Kazmaier, Eur. J.
Org. Chem. 2018, 6952–6965.
O
H
N
OH
5
CbzN
Me
CbzN
Me
O
NMM (2.5 equiv)
DMF, 0 °C
rt, 16 h
O
O
6ab
8ab
(89%)
B)
NO2
NO2
HCl•H2N-Ala-OMe (1.4 equiv)
BOP(1.4 equiv)
O
O
H
N
OH
BocN
Me
BocN
Me
NMM (2.4 equiv)
O
DMF, 0 °C
rt, 16 h
O
6ad
8ad
(94%)
6
7
(a) J. Kobayashi, M. Sato, M. Ishibashi, H. Shigemori, T.
Nakamura and Y. Ohizumi, J. Chem. Soc., Perkin Trans. 1,
1991, 2609–2611; (b) H. Uemoto, Y. Yahiro, H. Shigemori,
M. Tsuda, T. Takao, Y. Shimonishi and J. Kobayashi,
Tetrahedron, 1998, 54, 6719 –6724; (c) L. Junk and U.
Kazmaier, Angew. Chem. Int. Ed., 2018, 57, 11432–11435.
(a) E. Biron, J. Chatterjee, O. Ovadia, D. Langenegger, J.
Brueggen, D. Hoyer, H. A. Schmid, R. Jelinek, C. Gilon, A.
Hoffman and H. Kessler, Angew. Chem. Int. Ed. 2008, 47,
2595–25; (b) J. Chatterjee, C. Gilon, A. Hoffman and H.
Kessler, Acc. Chem. Res., 2008, 41, 1331-1342; (c) M. Luisa,
D. Gioia, A. Leggio, F. Malagrinò, E. Romio, C. Siciliano
and A. Liguori, Mini-Rev. Med. Chem., 2016, 16, 683–690.
(a) U. Kazmaier and J. Deska, Curr. Org. Chem., 2008, 12,
355–385; (b) W. Wang, M. M. Lorion, J. Shah, A. R. Kapdi
and L. Ackermann, Angew. Chem., 2018, 130, 14912–14930,
(Angew. Chem. Int. Ed., 2018, 57, 14700–14717).
(a) A. R. Dick, K. L. Hull and M. S. Sanford, J. Am. Chem.
Soc., 2004, 126, 2300–2301; (b) D. Shabashov and O.
Daugulis, Org. Lett., 2005, 7, 3657–3659; (c) R. Giri, J.
Liang, J. Lei, J. Li, D. Wang, X. Chen, I. C. Naggar, C. Guo,
B. M. Foxman and J. Yu, Angew. Chem. Int. Ed., 2005, 44,
7420–7424; (d) S. Aspin, A. S. Goutierre, P. Larini, R. Jazzar
and O. Baudoin, Angew. Chem. Int. Ed., 2012, 51, 10808–
10811; (e) E. T. Nadres, G. I. F. Santos, D. Shabashov and O.
Daugulis, J. Org. Chem., 2013, 78, 9689–9714; (f) P.
Servatius, L. Junk and U. Kazmaier, Synlett, 2019, in press.
DOI: 10.1055/s-0037-1612417.
Scheme 6
Subsequent peptide coupling of unusual amino acids 6.
without the formation of side products. The protocol is also
suitable to introduce highly functionalised side chains to C-
terminal alanines of dipeptides. The MTA directing group can
easily be removed, providing the free carboxylic acids and
allowing subsequent incorporation in more complex structures.
Conflicts of interest
There are no conflicts to declare.
8
9
Acknowledgements
Financial support from Saarland University is gratefully
acknowledged.
Notes and references
1
(a) K. Soloshonok and V. A. Izawa, Asymmetric Synthesis
and Application of α-Amino Acids, ACS Books, Washington,
2009; (b) A. B. Hughes, Amino Acids, Peptides and Proteins
in Organic Chemistry: Volume 3 - Building Blocks, Catalysis
and Coupling Chemistry, WILEY-VCH, 2010; (c) A. T.
Krueger and B. Imperiali, ChemBioChem 2013, 14, 788–799;
(d) P. Singh, K. Samanta, S. K. Das and G. Panda, Org.
Biomol. Chem., 2014, 12, 6297–6339.
(a) G. M. Coppola and H. F. Schuster, Asymmetric Synthesis:
Construction of Chiral Molecules Using Amino Acids, Wiley:
New York, 1987; (b) C. Najera and J. M. Sansano, Chem.
Rev. 2007, 107, 4584–4671; (c) M. A. Blaskovich, Handbook
on Syntheses of Amino Acids: General Routes for the
Syntheses of Amino Acids, Oxford University Press: New
York, 1st ed., 2010; (d) S. Mondal and S. Chowdhury, Adv.
Synth. Catal. 2018, 360, 1884–1912.
(a) D. Häbich, B. Hinzen, M. Brands, F. von Nussbaum and
S. Weigand, Angew. Chem. Int. Ed., 2006, 45, 5072–5129; (b)
F. Albericio and H. G. Kruger, Future Med. Chem., 2012, 4,
1527–1531; (c) F. Desriac, C. Jégou, E. Balnois, B. Brillet, P.
Le Chevalier and Y. Fleury, Mar. Drugs, 2013, 11, 3632–
3660.
(a) G. K. Ackers and F. R. Smith, Ann. Rev. Biochem., 1985,
54, 597–629; (b) D. Qi, C. M. Tann, D. Haring and M. D.
Distefano, Chem. Rev., 2001, 101, 3081–3111; (c) J. M.
Chalker, G. J. L. Bernardes, Y. A. Lin and B. G. Davis,
10 Reviews: (a) J. Yamaguchi, A. D. Yamaguchi and K. Itami,
Angew. Chem. Int. Ed., 2012, 51, 8960–9009; (b) A. F. M.
Noisier and M. A. Brimble, Chem. Rev., 2014, 114, 8775–
8806; (c) X. Lu, B. Xiao, R. Shang and L. Liu, Chin. Chem.
Lett., 2016, 27, 305–311; (d) G. He, B. Wang, W. A. Nack
and G. Chen, Acc. Chem. Res., 2016, 49, 635–645; (e) J. He,
M. Wasa, K. S. L. Chan, Q. Shao and J. Yu, Chem. Rev.,
2017, 117, 8754–5786.
2
11 Y. Feng and G. Chen, Angew. Chem. Int. Ed., 2010, 49, 958–
961.
3
4
12 (a) B. V. S. Reddy, L. R. Reddy and E. J. Corey, Org. Lett.,
2006, 8, 3391–3394; (b) D. Shabashov and O. Daugulis, J.
Am. Chem. Soc., 2010, 3965–3972; (c) J. He, S. Li, Y. Deng,
H. Fu, B. N. Laforteza, J. E. Spangler, A. Homs and J.-Q. Yu,
Science, 2014, 343, 1216–1220.
13 B. Wang, C. Lu, S. Zhang, G. He, W. A. Nack and G. Chen,
Org. Lett., 2014, 16, 6260–6263.
14 (a) H. Fu, P.-X. Shen, J. He, F. Zhang, S. Li, P. Wang, T. Liu
and J.-Q. Yu, Angew. Chem., 2017, 129, 1899–1902, (Angew.
Chem. Int. Ed., 2017, 56, 1873–1879); (b) T. Liu, J. X. Qiao,
This journal is © The Royal Society of Chemistry 20xx
Organic & Biomolecular Chemistry, 2019, 00, 1-3 | 5
Please do not adjust margins