Multiple multicomponent

Abstract How to access efficiently the macrocyclic structure remained to be a challenging synthetic topic. Although many elegant approaches/reactions have been developed, construction of diverse collection of macrocycles is stiU elusive. This chapter summarized the recently emerged research area dealing with multi-component synthesis of macrocycles, with particular emphasis on the approach named multiple multicomponent reaction using two bifunctional building blocks . 

Multiple Multicomponent Macrocyclization Using Two Bifunctional Building Blocks... 

Scheme 17 Synthesis of macrocycles by multiple multicomponent reactions including bifunctional building blocks (MiBs)...

O. Pando, S. Stark, A. Denkert, A. Porzel, R. Preusentanz, L. A. Wessjohann, J. Am. Chem. Soc. 2011, 133, 7692-7695. The multiple multicomponent approach to natural product mimics tubugis, N-substituted anticancer peptides with pico-molar activity. 

For recent examples of the synthesis of peptides and peptoids by the Ugi 4-CR, see (a) O. E. VerciUo, C. K. Z. Andrade, L. A. Wessjohann, Org. I tt. 2008, 10, 205-208. Design and synthesis of cychc RGD pentapeptoids by consecutive Ugi reactions, (b) O. Pando, S. Stark, A. Denkert, A. Porzel, R. Preusentanz, L. A. Wessjohann, J. Am. Chem. Soc. 2011, 133, 7692-7695. The multiple multicomponent approach to natural product mimics tubugis, V-substituted anticancer peptides with picomolar activity, (c) A. Fatima, S. Barreto, O. E. Vercillo, M. A. Birkett, J. C. Caulfield, L. A. Wessjohann, C. K. Z. Andrade, Org. Biomol. Chem. 2011, 9,5024-5027. Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions, (d) M. Abbas, L. A. Wessjohann, Org. Biomol. Chem. 2012, 10, 9330-9333. Direct synthesis of sensitive selenocysteine peptides by the Ugi reaction. For an application to peptide-peptoid podands by threefold Ugi-4CRs, see (e) D. G. Rivera, F. Leon, O. Concepcidn,... 

F. E. Morales, L. A. Wessjohann, Chem.-Eur. J. 2013, 19, 6417-6428. A multiple multicomponent approach to chimeric peptide-peptoid podands. 

G. Rivera, O. E. Vercillo, Chem. Rev. 2009, 109, 796-814. Multiple multicomponent macrocyclizations (MiBs) a strategic development toward macrocycle diversity, and references cited therein. 

For selected examples, see (a) G. Zhao, X. Sun, H. Bienayme, J. Zhu, J. Am. Chem. Soc. 2001, 123, 6700-6701. Activation of a terminal carboxylic acid by an internal oxazole a novel synthesis of macrocyclodepsipeptide. (b) P. Janvier, M. Bois-Choussy, H. Bienayme, J. Zhu, Angew. Chem. Int. Ed. 2003, 42, 811-814. A one-pot four-component (ABC ) synthesis of macrocycles, (c) L. A. Wessjohann, E. Ruijter, Mol. Divers 2005, 9, 159-169. Macrocycles rapidly produced by multiple multicomponent reactions including bifunctional building blocks (MiBs). (d) C. Bughin, G. Zhao, H. Bienayme, J. Zhu, Chem.-Eur. J. 2006, 12, 1174-1184. 5-Aminooxazole as an internal traceless activator of C-terminal carboxylic acid rapid access to diversely functionalized cyclodepsipeptides. (e) T. Pirali, G. C. Iron, J. Zhu, Org. Lett. 2006,8,4145 148. One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3 +2] cycloaddition. 

F. Leon, D. G. Rivera, L. A. Wessjohann, J. Org. Chem. 2008, 73, 1762-1767. Multiple multicomponent macrocychzations including bifunctional building blocks (MiBs) based on Staudinger and Passerini three-component reactions. 

Wessjoharai LA, Neves Filho RAW, Rivera DG (2012) Multiple multicomponent reactions with isocyanides. In Isocyanide chemistry. Wiley-VCH, Weinheim, pp 233-262... 

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