Synthesis of small molecules with specific function: I. Peptidocalix[4]arenes as molecular receptors. II. Towards the total synthesis of (-)-dihydroguaiaretic acid.

摘要

Part I. The association of organic molecules through noncovalent interactions is becoming increasingly important for the development of novel structures for information storage, molecular transport, sensing, and the assembly of supramolecular structures. In particular, the extensive research on the use of calix[n]arenes as synthetic receptors and hosts and the relative ease of synthesis and functionalization of these compounds makes them very attractive scaffolds. The goal is to synthesize peptidocalix[4]arenes in order to study their ability to form dimers and to catalyze reactions in various solvent systems and under variable conditions. This information will be used to design peptidocalix[4]arenes for use as catalysts for organic reactions and as capsules for molecular transport of compounds either across cell membranes or between solvent phases.; It is therefore desirable to prepare systems that will bind guests or under polar conditions, in order to develop hosts and capsules that will be compatible with a biological environment. Screening of a solid phase library of tetrasubstituted tripeptidocalix[4]arenes resulted in six compounds capable of catalyzing the hydrolysis of p-nitrophenyl acetate to p-nitrophenol. Additionally, disubstituted and tetrasubstituted alaninocalix[4]arenes have been found to associate through ionic interactions to form capsules in polar, protic solvents. These results are a very exciting first step towards the synthesis of peptidocalix[4]arene capsules for drug delivery or phase transfer catalysis.; Part II. The lignoid metabolite (-)-dihydroguaiaretic acid (DHGA), which was isolated from Saururus cernuus, was shown to deter crayfish feeding, indicating its potential use as a pesticide. Additionally, many lignans of similar structure to DHGA have been shown to possess a significant biological activity, and DHGA itself has shown the ability to inhibit the growth of Streptococcus species, Staphylococcus aureus, and Bacillus subtilis 9, making this a very appealing target for total synthesis. The total synthesis of DHGA will provide enough material to understand its ecological role and its biological activity.; The total synthesis of DHGA is currently underway and relies on an asymmetric oxidative homocoupling using an oxazolidinone as the auxiliary. Preliminary work has focused on the synthesis of the structurally more simple 1,4-bis-(3-methoxy-4-hydroxyhenyl)butane. These syntheses will also facilitate the synthesis of structural analogs.