| Summary: | H. pylori is a bacteria that infects a significant proportion of the human population. It is the primary agent responsible for gastric and duodenal ulcers and has been further linked with gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Eradication of H. pylori can cure these diseases; however the current therapies used are far from ideal. (+)-Spirolaxine methyl ether (15) exhibits potent activity against H. pylori and is therefore a promising drug candidate. The first enantioselective total synthesis of spirolaxine methyl ether (15) was achieved by Robinson and Brimble. This thesis reports the successful synthesis of eight analogues of spirolaxine methyl ether (15), with the aim of producing antibiotics with more pronounced activity than the parent natural product Specifically the goal is to obtain analogues where the length of the polymethylene carbon chain which links the spiroacetal and phthalide moieties is varied (Compounds 335-336) and at the same time replace the phthalide heterocycle with an indole (Compounds 337-339) and an oxindole (Compounds 340-342) ring systems. This strategy provides three sets of three analogues: one set with a longer polymethylene chain than the natural product and three different heterocycles (Compounds 336, 339, 342), a second set of three analogues with the same polymethylene chain length as in the natural product and the three different heterocycles (Compounds 338, 341) and finally a set of three compounds with a shorter polymethylene chain length than the natural product (Compounds 335, 337, 340) (Scheme 69). The information from the biological evaluation of these analogues of spirolaxine methyl ether (15) will be of considerable value to programs aimed at improving the anti-H. pylori profile of these compounds.
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