TA and TB toxins are host-specific phytotoxins produced by the fungus Alternaria alternata f. sp. Iycopersici, the causative agent of Alternaria stem canker disease in tomato. Both compounds are isolated as an equilibrium mixture of the esters formed by either the C(13) or C(14) hydroxy groups with the Re prochiral carboxy group of tricarballylic acid. The design and execution of syntheses for these toxins is necessary in order to study structure-function relationships for T A and TB toxins and their application as natural herbicides. The aim of the synthetic study presented in this thesis is to develop and implement a methodology for the synthesis of the C(1)-C(9) unit of the C17 amino¬pentol backbone of the TA and TB toxins with the required functional groups and appropriate stereochemistry using a chiral sulfoxide as an auxiliary to control the stereochemistry in key steps of the synthetic route. (2R,4S,5R,6R)-2,6-Dimethyloctane-1 ,4,5-triol, synthon B, and (2S,4R,5R)-1-aminononane-2,4,5,9-tetrol, synthon A were identified by retrosynthetic analysis of the C17 aminopentol backbone of TA toxin as key intermediates for a proposed synthesis. Further analysis of synthon B identified a C5 synthon that can be obtained from (2S)-malic acid by functional group transformations, chiral sulfoxide methodo¬logy and an appropriate protective group strategy. The work presented in the thesis shows that a protected intermediate corresponding to the abovementioned C5 synthon, (2S,4S)-2,4,5-trihydroxy:-pentanal can be prepared from (2S)-malic acid, but that using either Sharpless methodology or chiral sulfoxide methodology for the introduction of the third stereogenic centre and chain extension to a C9 unit, failed as a result of the steric crowding caused by the acetonide protecting group. As a result a different synthetic route is proposed. The results obtained in the work on TA toxin were applied to the synthesis of the C(1)-C(9) aminotetrol unit of the backbone of TB toxin. / Dissertation (MSc (Chemistry))--University of Pretoria, 2007. / Chemistry / unrestricted

TA and TB toxins are host-specific phytotoxins produced by the fungus Altemaria altemata f. sp. Iycopersici, the causative agent of stem canker disease in tomato. The two toxins are similar in structure: TB lacks the C(5) hydroxy group present in TA toxin. Both compounds are isolated as an equilibrium mixture of the two esters formed by either the C(13) or C(14) hydroxy groups of the (2S,4R,5R,11R,13S,14R,15R)-1-amino-11,15¬dimethylhepta-decane-2,4,5, 13, 14-pentol backbone with the Re prochiral carboxy group of tricarballylic acid. The synthesis for these toxins is necessary in order to study their structure-activity relationships. The aim of the synthetic study outlined in this dissertation is the development and implementation of methodology for the synthesis of the C(1)-C(9) unit of the C17 aminopentol backbone of TA toxin with the appropriate stereochemistry. Retrosynthetic analysis of the C17 aminopentol backbone of TA toxin identifies (2R,4S,-5R,6R)-2,6-dimethyloctane-1.4,5-triol, synthon B, and (2S,4R,5R)-1-amino¬nonane-2,4,5,9-tetrol, synthon A as key intermediates for the proposed synthesis. Further analysis of synthon A identifies the C9 synthon (2S,4R,5R)-nonane-1,2,4,5,9-pentol, as the target molecule which can be derived from the C7 synthon (2S,3R)-1,2-epoxyheptane-3,7¬diol. The work presented in this dissertation shows that the protected intermediate corresponding to the abovementioned C7 synthon, can be prepared from 1,5-pentanediol by a number of functional group trans-formations using appropriate protecting group strategy (O-TBS, O-TBDPS and O-benzyl groups) and introduction of the two stereogenic centres by using Sharpless epoxidation/kinetic resolution methodology. Nucleophilic opening of the terminal epoxide using cyanide was successful but using chiral sulfoxide methodology for the introduction of the third stereogenic centre and the concomitant one¬-carbon chain extension, failed: in the case of both an acetonide and a dibenzyl protected C8 intermediate a rearrangement occurred. Alternative methods for nucleophilic opening of the terminal epoxide ring and concomitant or subsequent chain extension were investigated and as a result a different synthetic route is proposed. / Dissertation (MSc (Chemistry))--University of Pretoria, 2006. / Chemistry / unrestricted