Project Details
Projekt
Total Synthesis of Antitumour Dithiodioxopiperazine Type Natural Products
Applicant
Dr. Tilman Lechel
Subject Area
Organic Molecular Chemistry - Synthesis and Characterisation
Term
from 2009 to 2011
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 161593460
The project objective is the total synthesis of the macrocycle MCP1001B(1). This naturally occuring compound shows potent antitumour activity against a human prostate cancer cell line. The total synthesis of MCP1001B might be accessible via three fragments. A retrosynthetic approach to the initial target 1 is shown in Scheme 1. The first disconnections are the disulfide bridge, the ester and biaryl linkages to give the acid fragment 2a or 2b and the dioxopiperidine-dihydrooxepin 3. In a forward sense, the ester linkage could be formed first and the macrocycle could be obtained by an intramolecular biaryl ether formation by transition metal catalysed cross coupling or a facile nucleophilic aromatic substitution reaction between the phenolate 3 and the ortho-nitrofluoride 2b. The second approach would require conversion of the nitro group into a methyl ether by diazotization, hydroxide diplacement and methylation. The synthesis of the piperidine fragment 3 would involve a peptide coupling between acid 4 and the amine 5 hopefully, without protection of the secondary amine in 3. The dipeptide product should then undergo cyclisation to the dioxopiperazine. The acid fragment 3 could be obtained by a biosynthesis inspired approach while the synthesis of amine 4 relies on a salen catalysed asymmetric aldol reaction protocol.
DFG Programme
Research Fellowships
International Connection
Australia
