Synthetic and Structural Studies in the Natural Product Field

This thesis consists of six chapters, the first of which is a General Introduction dealing with (i) the nature of secondary metabolites and (ii) the terpenoids and aromatic constituents of the Hepaticae (liverworts). Chapter 2 describes the synthesis of conocephalenol, an unusual sesquiterpenoid constituent of the liverwort Conocephalum conicum. Michael addition of 5,5-dimethylcyclohexane-1,3-dione to methyl vinyl ketone afforded a triketone which on McMurry reduction using TiCl3/ZnCu, gave 1,6,6-trimethyl-2,3,4,5,6,7-hexahydro-4H-indene-4-one. Hydrogenation of this hydrindenone occurred stereoselectively and furnished the corresponding cis-hydrindanone. Reaction of this hydrindanone with alpha-lithio ethoxy vinyl ether afforded, after subsequent hydrolysis of the product in dilute HCl, a mixture of two diastereomeric alpha-hydroxy ketones. One of these, on dehydration with SOCl2 gave 4-acetyl-1,6,6-trimethyl 2,3,5,6,7,7a hexahydroindene which reacted with MeLi to give conocephalenol. The relative stereochemistry of 1-H and 7a-H in conocephalenol therefore must be trans. Chapter 3 is concerned with a synthetic approach to the bicyclic system of tamariscol, an unusual sesquiterpenoid alcohol from the liverwort Frullania tamarisci. Alkylation of cyclohexane-1,3-dione with methyl vinyl ketone afforded a triketone which was transferred into l-methyl-2,3,4,5,6,7-hexahydro-4H-inden-4-one using the McMurry reaction. Methylation followed by stereoselective hydrogenation yielded a mixture of dimethylhydrindanones, one of which proved to be identical with a degradation product of tamariscol. This confirmed the trans relative stereochemistry of 1-H and the adjacent bridgehead proton. Chapter 4 describes the structural elucidation of pakyonol, a new macrocyclic bisbibenzyl diether from the liverwort Mannia fragrans. The structure was assigned on the basis of detailed COSY, NOE and multiple selective irradiation experiments. Pakyonol represents a new bisbibenzyl substitution pattern, the first example to be isolated from the Hepaticae. The synthesis of 3,5-dimethoxy-4-(3-methyl-2-butenyl)-bibenzyl is described in Chapter 5. The demethoxy derivative occurs in several Radula species. A Wittig reaction of 3,5-dimethoxybenzaldehyde and benzylphosphonium chloride afforded a stilbene mixture which on hydrogenation gave 3,5-dimethoxybibenzyl. Alkylation of this with n-BuLi and isoprenyl bromide gave the desired product in good yield. Chapter 6 describes the structural elucidation of five partially-acetylated derivatives of 1-O-dodecanyl alpha-L-rhamnopyranosyl-(1→3)-alpha-L-rhamnopyranosyl-(1→3)-alpha-L-rhamnopyranosyl-(1→4)-alpha-L-rhamnopyranoside, isolated from the stem bark of Cleistopholis glauca (Annonaceae). Their structures were elucidated by a combination of COSY, delayed COSY and FAB Mass spectroscopy. The trisaccharide 1-O-dodecanyl alpha-L-2,3,4-triacetylrhamnopyranosyl-(1-K3)-alpha-L-4-acetylrhamnopyranosyl-(1→4)-alpha-L-rharanopyranoside was also isolated