Novel macrocyclic systems in asymmetric phase-transfer catalysis

2014 - 2015In the great realm of organic synthesis, phase-transfer catalysis (PTC) is a well recognized methodology which plays a key role both in industry and academia research. This process involves reactions that take place between reagents which are located in different phases, for example an inorganic water-soluble reagent and a substrate soluble in the organic phase. Considering the well-defined advantages of asymmetric phase-transfer catalysis as a powerful method for organic synthesis, the aim of this research project is to introduce novel macrocycle systems as new and efficient catalysts in this field. First of all, considering the advantages of the easy synthetic process for the preparation of cyclopeptoids, their well-explored complexation properties and the preliminary study on the application as phase-transfer catalysts, the idea is to deeply investigate their use in PTC. The advantages of the solid phase synthesis, such as the easy purification of the intermediates and the modular nature of the products, make cyclopeptoids ideal candidates for the discovery of new catalytic systems, as it is possible to incorporate a wide variety of functionalities inside the backbone of the macrocycle in an expeditious way. As a consequence, a library of peptoid-based chiral macrocycles of different size, decorated with alternating residues of L-Proline and different aromatic side chains, will be prepared and used for enantioselective alkylation reactions. The scope of this project extends also to the investigation of novel chiral calixarenes. However, in this case, the idea is to exploit the ability of calixarenes to form host-guest complexes with alkali cations. The study is also devoted to further explore the potential of crown ethers in new catalytic processes. The second chapter focus first on the synthesis of novel chiral cyclopeptoids and then on their application in asymmetric phase-transfer alkylations, in particular for the enantioselective synthesis of α-amino acids. Afterwards the application of new designed calixarenes for the same alkylation reaction is described. Finally the application of cyclopeptoidic systems in the enantioselective alkylation of 2-aryl-oxazoline-4 carboxylic acid esters is discussed. The third chapter describes the application of crown ethers in phase-transfer processes. For this purpose a diasteroselective methodology for the synthesis of γ-substituted butenolides by a direct vinylogous Mukayama-Michael reaction has been developed. [edited by author]L’attività di ricerca svolta dalla Dr.ssa Schettini Rosaria ha riguardato la sintesi e l’applicazione di nuovi sistemi macrociclici nella catalisi asimmetrica a trasferimento di fase. In particolare, il progetto di dottorato è stato incentrato sulla sintesi di nuovi sistemi chirali di natura ciclopeptoidica impiegati come catalizzatori nel campo asimmetrico. Nel corso del dottorato nuovi sistemi calixarenici chirali sono stati impiegati nel medesimo campo. L’ultima parte del progetto ha riguardato l’impiego di catalizzatori facilmente reperibili in commercio, gli eteri corna. Essi sono stati impiegati con successo in una reazione altamente diastereoselettiva. Durante il corso di dottorato, la dott.ssa Schettini Rosara ha seguito costantemente le attività didattiche previste nel progetto. [a cura dell'autore]XIV n.s

Synthesis and properties of linear and cyclic peptoids

2010 - 2011Le strutture e le attività metaboliche di tutte le cellule si basano su una vasta gamma di molecole comprendenti: amminoacidi, carboidrati, lipidi e nucleotidi, insieme alle forme polimeriche di questi composti. Ognuna di queste molecole presenta una caratteristica struttura chimica, una determinata capacità di interagire con altre molecole e una specifica funzione fisiologica. È stato visto che la struttura chimica e le attività fisiologiche sono strettamente correlate tra loro, a tal punto che senza una giusta conformazione le suddette attività possono venir meno. Pertanto, negli ultimi anni si sta investigando su composti che possano mimare le molecole biologiche in tutte le loro funzioni e allo stesso tempo avere le proprietà di un biopolimero non naturale. Una di queste classi di molecole biologiche è quella dei nucleotidi, i quali prendono parte attiva in molti aspetti della vita cellulare, infatti partecipano a reazioni di biosintesi e di ossidoriduzione, al trasferimento di energia, svolgono una serie di funzioni strutturali e catalitiche. Un ruolo ancora più importante rivestono i loro polimeri, gli acidi nucleici, ovvero DNA ed RNA. In accordo con il dogma centrale della biologia molecolare, infatti, la natura ha scelto questi due composti per l’immagazzinamento (DNA) e il trasferimento (RNA) dell’informazione genetica nelle cellule viventi... [abstract a cura dell'autore]X n.s

New insights into peptoids' chemistry: synthesis, characterization and properties

2014 - 2015My PhD research activity aimed to enrich the realm of peptoids1 with novel compounds and new insights into their behavior and properties, investigating their potential applications. A new class of cyclic “arylopeptoids” was synthesized by the insertion of an aromatic ring and a methylene unit into the peptoidic backbone (Chapter 2). Tested as ion transporters of alkali metal cations, protons, and a series of anions through a phospholipid membrane, they highlighted the strong influence of the size of the macrocycle on the ion transport activity. Exploiting the ion complexation properties of cyclic peptoids, two cyclic hexamers were synthesized with three carboxyethyl side chains each, to promote the formation of Gd3+-complex as MRI-probes (Chapter 3). When carboxyethyl side chains were alternated with methoxyethyl side chains, the cyclic peptoid coordinated Gd3+ and displayed good relaxometric properties, as revealed by 1H-relaxometric investigations.2 The versatility of peptoids enabled us to explore the field of glycoscience as well. A library of cyclic peptoids, ranging from 4-mer to 16-mer, with appended propargyl groups was synthesized and underwent click chemistry with DNJ azido-derivatives (Chapter 4). This is the first example of cyclopeptoid-based iminosugar click-clusters that showed activity towards α-mannosidases inhibition and the highest multivalent effect in the correspondence of the 36-valent ligand.3 This impressive outcome is the result of the modular synthetic approach of peptoids that enables for the insertion of an unlimited numbers and types of side chains.4 Taking advantage of such feature, we synthesized a library of cyclic hexapeptoids with methoxyethyl and propargyl side chains, varying in the relative content and positions (Chapter 5). Studying their role in the solid-state assembly of cyclic hexapeptoids, they showed to promote a columnar arrangement in which the propargyl groups are the pillars and the methoxyethyl chains provide intercolumnar interactions and side-by-side contacts.5 [edited by author]XIV n.s

Cyclic α,β-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference

The presence of at least one <i>N</i>-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The <i>ctct</i> amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid <b>8</b> is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs)

Cyclic alpha,Beta-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference.

International audienceThe presence of at least one N-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The ctct amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid 8 is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs)

Cyclic α,β-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference

The presence of at least one <i>N</i>-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The <i>ctct</i> amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid <b>8</b> is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs)