Author: Nasim EsmatiPublisher:
ISBN:
Category : Bioactive compounds
Languages : en
Pages : 164
Book Description
Generating molecular complexity and molecular diversity in a simple and rapid process has become one of the most challenging yet increasingly popular concepts in organic chemistry over the past few years. Taking this into consideration, the design of various types of chemical building blocks to prepare a small library of natural products or biological active molecules has become a significant objective. To fulfill these objectives, one can take advantage of multi component reactions (MCRs), in which three or more starting materials react to form a single product, where basically all or most of the atoms contribute to the newly formed product. MCRs have the ability of combining commercially available or readily accessible multiple starting materials with a variety of functionalities in one-step and then invoking post modification steps, like various kinds of ring formations and rearrangements. The experimental simplicity of one-pot procedures can give access to a diverse library of compounds rapidly, which makes the procedure more advantageous over multistep syntheses. All these important factors provide the opportunity to work on combinatorial chemistry which counts as a fundamental phenomenon in finding novel molecules for medicinal chemistry. The development and application of multicomponent reactions have attracted much attention in recent years since they are very useful synthetic tools for synthesize of potential pharmaceutically bioactive scaffolds. Post modified transformation of MCRs have great importance for accessing the synthetic building blocks for complex natural products and their analogues to investigate their possibility in treating various diseases. In the first project, we attempted the synthesis and biological study of Derivatives of the herbicide thaxtomin, through Ugi/keto-amide cyclization and Ugi/Dess-Martin/keto-amide cyclization sequences. The Ugi reaction was utilized with 3-nitrobenzaldehyde, indole-3-carboxaldehydes, phenyl lactic acid, methylamine, and methyl isocyanide to prepare dipeptides which then underwent oxidation to a- ketoamide intermediates followed by subsequent alkaline mediated keto-amide cyclization to syn and anti hemiaminal DKPs. In the second project, we reported a one-pot, two-step, total synthesis of naturally occurring Xenortides A, B, C and D, (Xens A-D) isolated from the bacterium Xenorhabdus nematophila, and an entire complimentary set of stereoisomers. The syntheses were accomplished utilizing an isocyanide-based Ugi 4-CR followed by facile N-Boc deprotection. The reaction sequence takes advantage of the chiral pool of N-Boc protected amino acids (L-Leu/Val and D-Leu/Val) with aryl isocyanides, phenyl acetaldehyde and methylamine giving the desired Xens A-D and all subsequent stereoisomers. Moreover, this focused library of naturally occurring Xens A-D and their subsequent stereoisomers were screened for cytotoxicity against a panel of epithelial cancer cell lines as well as normal cell lines.
