Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

An Efficient Chemical Synthesis of Lassomycin Enabled by an On-Resin Lactamisation–Off-Resin Methanolysis Strategy and Preparation of Chemical Variants

Paul W. R. Harris A B E , Gregory M. Cook B D , Ivanhoe K. H. Leung A and Margaret A. Brimble A B C
+ Author Affiliations
- Author Affiliations

A School of Biological Sciences, The University of Auckland, 3A Symonds Street, Auckland 1010, New Zealand.

B Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 3A Symonds Street, Auckland 1010, New Zealand.

C School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand.

D Department of Microbiology and Immunology, School of Medical Sciences, University of Otago, 720 Cumberland Street, Dunedin 9054, New Zealand.

E Corresponding author. Email: paul.harris@auckland.ac.nz

Australian Journal of Chemistry 70(2) 172-183 https://doi.org/10.1071/CH16499
Submitted: 7 September 2016  Accepted: 7 October 2016   Published: 28 October 2016

Abstract

An efficient synthesis of the naturally occurring cyclic peptide lassomycin that bears a unique Asp–Gly isopeptide bond and a C-terminal methyl ester is described. On-resin cyclisation between 1Gly and side chain 8Asp and a subsequent solution-phase transesterification reaction afforded synthetic lassomycin in high yield. Several analogues were also prepared using the optimised methodology. None of the cyclised peptides, including the synthetic natural product, exhibited any significant activity against Mycobacterium tuberculosis. Comparison of the spectroscopic data for synthetic lassomycin with naturally occurring lassomycin concluded they were otherwise identical.


References

[1]  A. Zumla, P. Nahid, S. T. Cole, Nat. Rev. Drug Discov. 2013, 12, 388.
         | CrossRef | 1:CAS:528:DC%2BC3sXms1Kmsrk%3D&md5=3dd48e707c080f0ae1ac0a6ab2e70234CAS | 23629506PubMed | open url image1

[2]  Global Tuberculosis Report 2012 (World Health Organization: Geneva).

[3]  (a) J. Cohen, Science 2013, 339, 130.
         | CrossRef | 1:CAS:528:DC%2BC3sXhtFCjt78%3D&md5=7e7a4dd4f6a10a49a3f9e418805ea2a5CAS | 23307714PubMed | open url image1
      (b) K. Andries, P. Verhasselt, J. Guillemont, H. W. H. Gohlmann, J. Neefs, H. Winkler, J. Gestel, P. Timmerman, M. Zhu, E. Lee, P. Williams, D. de Chaffoy, E. Huitric, S. Hoffner, E. Cambau, C. Truffot-Pernot, N. Lounis, V. Jarlier, Science 2005, 307, 223.
         | CrossRef | open url image1

[4]  E. Gavrish, C. S. Sit, S. Cao, O. Kandror, A. Spoering, A. Peoples, L. Ling, A. Fetterman, D. Hughes, A. Bissell, H. Torrey, T. Akopian, A. Mueller, S. Epstein, A. Goldberg, J. Clardy, K. Lewis, Chem. Biol. 2014, 21, 509.
         | CrossRef | 1:CAS:528:DC%2BC2cXltFeqtLc%3D&md5=a40502955d5a61c48d109738aa2c7c37CAS | 24684906PubMed | open url image1

[5]  (a) I. Kavianinia, L. Kunalingam, P. W. R. Harris, G. M. Cook, M. A. Brimble, Org. Lett. 2016, 18, 3878.
         | CrossRef | 1:CAS:528:DC%2BC28Xht1ekt77P&md5=362608d818e9a556864fb586e797b22cCAS | 27467118PubMed | open url image1
      (b) L. M. De Leon Rodriguez, H. Kaur, M. A. Brimble, Org. Biomol. Chem. 2016, 14, 1177.
         | CrossRef | open url image1

[6]  W. Weber, W. Fischli, E. Hochuli, E. Kupfer, E. K. Weibel, J. Antibiot. 1991, 44, 164.
         | CrossRef | 1:CAS:528:DyaK3MXitVehsL0%3D&md5=f83788645e4ab33ad685090f997e4915CAS | 1849131PubMed | open url image1

[7]  (a) M. O. Maksimov, S. J. Pan, A. J. Link, Nat. Prod. Rep. 2012, 29, 996.
         | CrossRef | 1:CAS:528:DC%2BC38XhtFKnsbnE&md5=2562ee9fa476d0364a41a0c1593fc7e4CAS | 22833149PubMed | open url image1
      (b) J. D. Hegemann, M. Zimmerman, X. Xie, M. A. Marahiel, Acc. Chem. Res. 2015, 48, 1909.
         | CrossRef | open url image1
      (c) N. Zhao, Y. Pan, Z. Cheng, H. Liu, Amino Acids 2016, 48, 1347.
         | CrossRef | open url image1

[8]  K. J. Rosengren, R. J. Clark, N. L. Daly, U. Gçransson, A. Jones, D. J. Craik, J. Am. Chem. Soc. 2003, 125, 12464.
         | CrossRef | 1:CAS:528:DC%2BD3sXntlyqt7o%3D&md5=d9b0ed94cdad852c3e8d06a801107e15CAS | 14531690PubMed | open url image1

[9]  (a) S. Duquesne, D. Destoumieux-Garzon, S. Zirah, C. Goulard, J. Peduzzi, S. Rebuffat, Chem. Biol. 2007, 14, 793.
         | CrossRef | 1:CAS:528:DC%2BD2sXotlSnu78%3D&md5=bfdfb063aa88f08baef103421590b9f8CAS | 17656316PubMed | open url image1
      (b) K. P. Yan, Y. Li, S. Zirah, S. Goulard, T. A. Knappe, M. A. Marahiel, S. Rebuffat, ChemBioChem 2012, 13, 1046.
         | CrossRef | open url image1

[10]  M. Amblard, J. Fehrentz, J. Martinez, G. Subra, Mol. Biotechnol. 2006, 33, 239.
         | CrossRef | 1:CAS:528:DC%2BD28XmvFygsb4%3D&md5=f40be585eb40650b82656819f1de153aCAS | 16946453PubMed | open url image1

[11]  E. Atherton, C. J. Logan, R. C. Sheppard, J. Chem. Soc., Perkin Trans. 1 1981, 538.
         | CrossRef | 1:CAS:528:DyaL3MXhslGmsLg%3D&md5=b562616b5b4bda16eae0e2782d259935CAS | open url image1

[12]  F. Albericio, G. Barany, Int. J. Pept. Protein Res. 1985, 26, 92.
         | CrossRef | 1:CAS:528:DyaL28XhsV2gurw%3D&md5=a2a1e0b5f97d3566ae5e6983acb99f8bCAS | 4055231PubMed | open url image1

[13]  H. Rink, Tetrahedron Lett. 1987, 28, 3787.
         | CrossRef | 1:CAS:528:DyaL1cXktlyhs7Y%3D&md5=4ecf32ad727744d1c2cdbb808c894299CAS | open url image1

[14]  S. Lear, T. Munshi, A. S. Hudson, C. Hatton, J. Clardy, J. A. Mosely, T. J. Bull, C. S. Sit, S. L. Cobb, Org. Biomol. Chem. 2016, 14, 4534.
         | CrossRef | 1:CAS:528:DC%2BC28XmsF2nsL8%3D&md5=b18fb128d72d64e3a11d993fe444bfa2CAS | 27101411PubMed | open url image1

[15]  C. Yue, J. Terry, P. Potier, Tetrahedron Lett. 1993, 34, 323.
         | CrossRef | 1:CAS:528:DyaK3sXitFenu7c%3D&md5=ee713dc0ee74b652bd6e1cc95b6f0678CAS | open url image1

[16]  P. W. R. Harris, S. H. Yang, M. A. Brimble, Tetrahedron Lett. 2011, 52, 6024.
         | CrossRef | 1:CAS:528:DC%2BC3MXht12qs7fM&md5=f0c739c91bf3c88bb1436be93cc550d8CAS | open url image1

[17]  (a) W. R. Abd-Elgaliel, F. Gallazzi, S. Z. Lever, J. Pept. Sci. 2007, 13, 487.
         | CrossRef | 1:CAS:528:DC%2BD2sXot1WlsLc%3D&md5=5ae16b95e88b804a4bfa14cc3c9ad97dCAS | 17559059PubMed | open url image1
      (b) J. Hansen, F. Diness, M. Meldal, Org. Biomol. Chem. 2016, 14, 3238.
         | CrossRef | open url image1

[18]  Available from Merck Millipore, cat. no. 852086.

[19]  R. Chen, T. J. Tolbert, J. Am. Chem. Soc. 2010, 132, 3211.
         | CrossRef | 1:CAS:528:DC%2BC3cXhvF2ks7g%3D&md5=b47004a1c36fea7b3be397b6868d1be6CAS | 20158247PubMed | open url image1

[20]  F. Albericio, J. M. Bofill, A. El-Faham, S. A. Kates, J. Org. Chem. 1998, 63, 9678.
         | CrossRef | 1:CAS:528:DyaK1cXns1ymtL8%3D&md5=4cf597e14171bb7ffb3b671ac2573ab5CAS | open url image1

[21]  (a) G. M. Williams, K. Lee, X. Li, G. J. S. Cooper, M. A. Brimble, Org. Biomol. Chem. 2015, 13, 4059.
         | CrossRef | 1:CAS:528:DC%2BC2MXjsFCqs7k%3D&md5=d915b0da04bbcb5a19a50bafb440dd26CAS | 25731597PubMed | open url image1
      (b) M. A. Hossain, A. Belgi, F. Lin, S. Zhang, F. Shabanpoor, L. Chan, C. Belyea, H. T. Truong, A. R. Blair, S. Andrikopoulos, G. W. Tregear, J. D. Wade, Bioconjug. Chem. 2009, 20, 1390.
         | CrossRef | open url image1

[22]  F. A. Robey, R. L. Fields, Anal. Biochem. 1989, 177, 373.
         | CrossRef | 1:CAS:528:DyaK3cXjs1Chug%3D%3D&md5=d1608d74defa56c5ba554a4ae8494ba8CAS | 2729557PubMed | open url image1

[23]  Available from Merck Millipore, cat. no. 531147.

[24]  R. Soudy, L. Wang, K. Kaur, Bioorg. Med. Chem. 2012, 20, 1794.
         | CrossRef | 1:CAS:528:DC%2BC38XhvFeis7k%3D&md5=4c09c21169cac250694f30f812d01a5cCAS | 22304849PubMed | open url image1



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