Approaches to the synthesis of guanidine containing natural products

• Main Author: Buck, Matthew
• Other Authors: Murphy, Patrick
• Published: Bangor University 2017
• Subjects: 540
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.731744

The thesis is divided into three parts: A: synthetic approach to the LHS of cylindrospermopsin: An intermediate (3R,4S)-6-(benzyloxy)-4-((tert-butyl dimethyl silyl)oxy)-3-methyl hexane-1,2-diol (I)(Figure I) for the synthesis of the alkaloid cylindrospermopsin was prepared in 6 steps from propane-1,3-diol. However, the key step in the synthesis the Sharpless asymmetric dihydroxylation of an alkene using AD-mix ß gave very poor diastereoselectivity. An intermediate Brown crotylation step gave a 93:7 selectivity as shown by the formation of mandelate esters and their NMR analysis. B: The total synthesis of Tiruchanduramine: Tiruchanduramine (II) was prepared in a convergent manner over 8 steps in 4.5% overall yield from the known ßcarboline carboxylic acid (III) and the cyclic guanidine (IV), which was prepared in 7 steps from 3-amino-1-propanol. The two fragments were coupled using CDI in THF/DMF. C: Approaches to the synthesis of nitensidine E: The intermediate thiourea (V) was prepared in 5-steps from cis-1,4-butene diol in an attempt to investigate the Pd0 mediated cyclisation of N-Methoxyguanidines.