Combinatorial Synthesis of Macrocycles by Multiple Multicomponent Macrocyclization Including Bifunctional Building Blocks (MiB)

Abstract

Small libraries of peptoid-based macro(multi)cycles were produced by applying combinatorial principles to the MiB methodology. This combinatorial approach features the incorporation of varied building blocks into the resulting macrocycles by mixing all the components in the same reaction pot. Both skeletal and appendage diversity could be generated in one shot due to the multicomponent nature of the system. HPLC and ESI-MS analyses showed a well-distributed composition of the libraries and revealed the presence of all possible macrocycles resulting from the different combinations of building blocks, especially of members with differentially substituted bridges not available by any other one-pot ­approach.

combinatorial synthesis - multicomponent reactions - Ugi reaction - macrocycles - cryptands

References

<A NAME="RG31406ST-1A">1a</A> Gibson SE. Lecci C. Angew. Chem. Int. Ed.  2006,  45:  1364 

<A NAME="RG31406ST-1B">1b</A> Wessjohann LA. Ruijter E. Rivera DG. Brandt W. Mol. Diversity  2005,  9:  171 

<A NAME="RG31406ST-1C">1c</A> Arico S. Chang T. Cantrill SJ. Khan SI. Stoddart JF. Chem. Eur. J.  2005,  11:  4655 

<A NAME="RG31406ST-1D">1d</A> Schalley CA. Wielandt T. Bruggeman J. Vögtle F. Top. Curr. Chem.  2004,  248:  141 

<A NAME="RG31406ST-1E">1e</A> Newman DJ. Cragg GM. Snader KM. Nat. Prod. Rep.  2000,  17:  215 

<A NAME="RG31406ST-2A">2a</A> Wessjohann LA. Ruijter E. Top. Curr. Chem.  2005,  243:  137 

<A NAME="RG31406ST-2B">2b</A> Blankenstein J. Zhu J. Eur. J. Org. Chem.  2005,  1949 

<A NAME="RG31406ST-2C">2c</A> Nicolaou KC. J. Org. Chem.  2005,  70:  7007 

<A NAME="RG31406ST-2D">2d</A> Schalley CA. Reckien W. Baytekin B. Vögtle F. Chem. Eur. J.  2004,  10:  4777 

<A NAME="RG31406ST-2E">2e</A> Lambert JN. Mitchell JP. Roberts KD. J. Chem. Soc., Perkin Trans. 1  2001,  471 

<A NAME="RG31406ST-2F">2f</A> de Greef M. Abeln S. Belkasmi K. Dömling A. Orru RVA. Wessjohann LA. Synthesis  2006,  3977 

<A NAME="RG31406ST-3A">3a</A> Boger DL. Desharnais J. Capps K. Angew. Chem. Int. Ed.  2003,  42:  4138 

<A NAME="RG31406ST-3B">3b</A> Combinatorial Chemistry: A Practical Approach   Fenniri H. Oxford University Press; New York: 2000. 

<A NAME="RG31406ST-4A">4a</A> Corbett PT. Leclaire J. Vial L. West KR. Wietor J.-L. Sanders JKM. Otto S. Chem. Rev.  2006,  106:  3652 

<A NAME="RG31406ST-4B">4b</A> Rowan SJ. Cantrill SJ. Cousin GRL. Sanders JKM. Stoddart JF. Angew. Chem. Int. Ed.  2002,  41:  898 

<A NAME="RG31406ST-5A">5a</A> Rivera DG. Wessjohann LA. J. Am. Chem. Soc.  2006,  128:  7122 

<A NAME="RG31406ST-5B">5b</A> Wessjohann LA. Voigt F. Rivera DG. Angew. Chem. Int. Ed.  2005,  44:  4785 

<A NAME="RG31406ST-5C">5c</A> Wessjohann LA. Ruijter E. Mol. Diversity  2005,  9:  159 

<A NAME="RG31406ST-5D">5d</A> Wessjohann LA. Rivera DG. Coll F. J. Org. Chem.  2006,  71:  7521 

<A NAME="RG31406ST-5E">5e</A> Michalik D. Schaks A. Wessjohann LA. Eur. J. Org. Chem.  2007,  149 

<A NAME="RG31406ST-6A">6a</A> Beck B. Larbig G. Mejat B. Magnin-Lachaux M. Picard A. Herdtweck E. Dömling A. Org. Lett.  2003,  5:  1047 

<A NAME="RG31406ST-6B">6b</A> Sello JK. Andreana PR. Lee D. Schreiber SL. Org. Lett.  2003,  5:  4125 

<A NAME="RG31406ST-6C">6c</A> Cristau P. Vors J.-P. Zhu J. Tetrahedron Lett.  2003,  44:  5575 

<A NAME="RG31406ST-6D">6d</A> Owens TD. Araldi GL. Nutt RF. Semple JE. Tetrahedron Lett.  2001,  42:  6271 

<A NAME="RG31406ST-6E">6e</A> Zhao G. Sun X. Bienaymé H. Zhu J. J. Am. Chem. Soc.  2001,  123:  6700 

<A NAME="RG31406ST-7A">7a</A> Dömling A. Chem. Rev.  2006,  106:  17 

<A NAME="RG31406ST-7B">7b</A> Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 

<A NAME="RG31406ST-8">8</A> Kessler H. Angew. Chem., Int. Ed. Engl.  1982,  21:  512 

<A NAME="RG31406ST-9">9</A> Brahmachary E. Ling FH. Svec F. Fréchet JMJ. J. Comb. Chem.  2003,  5:  441 ; and references therein

<A NAME="RG31406ST-10A">10a</A> Bowman-James K. Acc. Chem. Res.  2005,  38:  671 

<A NAME="RG31406ST-10B">10b</A> Llinares JM. Powell D. Bowman-James K. Coord. Chem. Rev.  2003,  240:  57 

<A NAME="RG31406ST-10C">10c</A> Amendola V. Fabbrizzi L. Mangano C. Pallavacini P. Poggi A. Taglietti A. Coord. Chem. Rev.  2001,  219-221:  821 

<A NAME="RG31406ST-10D">10d</A> Lehn J.-M. Supramolecular Chemistry: Concepts and Perspectives   Wiley-VCH; Weinheim: 1995. 

<A NAME="RG31406ST-10E">10e</A> Yoon SS. Still WC. J. Am. Chem. Soc.  1993,  115:  823