Natural The Product Microsclerodermins, And Macrocidin A Synthesis Of Research

Cyclopeptides exist broadly in nature, especially in marine sponges. Many cyclopeptides with unique structures have been recently isolated. These compounds showed a wide range of biological activities which included antitumor, cytotoxicity, and antimicrobial actions. Microsclerdermins have been isolated from the sponge of Microscleroderma sp by Faulkner and co-workers, which displayed potent antifungal activities against Candida albicans.In the first Chapter of this thesis, we demonstrated our synthesis of AMMTD, a complex component of Microsclerdermin A/B. Started from gluconolactone, we set up five consecutive stereogenic centers of AMMTD by using Sharpless epoxidation, ring opening selectively with lithium dimethylcuprate, and S_N2 reaction to introduce the 3-amino group as key steps. After elaborated the trans C-C double bond via Kocienski-Julia reaction, the desired AMMTD unit was obtained via ordinary transformations. The overall yield was 5.4% for 23 linear steps. In addition, we also synthesized APTO, a complex component of Microsclerdermin C/D using the same strategy. Furthermore, during the above synthetic studies, we also found sodium amalgam was a useful agent for reducing azide to amine, which was applicable for various alkyl and aryl azides bearing different functional groups.Tetramic acids are important heterocyclic compounds that have recently attracted a great deal of interest because many of compounds exhibited important biological activities. Macrocidin A is a macrocyclic tetramic acid with herbicidal activity that isolated from the culture of Phoma macrostoma.In the second chapter of this thesis, our synthetic studies to macrocidin A were discussed. Started from D-tyrosine, we obtained the tetramic acid 96 using Jouin reaction. The assembly of the second fragment 109 was stared from 1,4-butandiol,using asymmetric alkylation reaction developed by Oppolzer as a key step. Coupling of the tetramic acid 96 with 109 provided the key intermediate 110 according to Yoshii's procedure. After remove protective group and Sharpless epoxidation, we obtained the key intermediate 113. Its macrocyclization to form the final product is in progress.