Chemical studies on the origin of secondary metabolites in selected marine invertebrates

• Main Author: Kubanek, Julia Marie
• Format: Others
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/10215

Precursor incorporation experiments with several widespread species of Northeastern Pacific Ocean dorid nudibranchs have led to the conclusion that each species studied is capable of de novo biosynthesis. Incorporation studies with [1,2- 1 3C2] acetate, [l,2-13C2,18Oi] acetate, and [2-13C] mevalonate were used to demonstrate the biosynthesis of the sesquiterpenoid albicanyl acetate (18), and the sesterterpenoids cadlinaldehyde (19) and luteone (20) by Cadlina luteomarginata. Quantitative analysis of C NMR data showed that only a small turnover of metabolite took place but that the newly formed molecules had extremely high levels of label incorporation. As a by-product of the examination of biosynthesized metabolites of C. luteomarginata, a novel diterpenoid metabolite, seco-spongian 22, was isolated and identified. [Chemical models not reproduced] A study of Californian specimens of C. luteomarginata indicated that the three biosynthesized metabolites are present across its geographic range. Examination of individual C. luteomarginata specimens from one B.C. population revealed significant variation in metabolite concentration between individuals and between tissues of each individual. Incorporation experiments with [1,2- 1 3C2] acetate were also used to demonstrate the de novo biosynthesis of acanthodoral (28) by Acanthodoris hudsoni, a metabolite previously known only from the related nudibranch A. nanaimoensis. Attempts to incorporate 180 labels into the aldehyde oxygen atoms of nanaimoal (24), isoacanthodoral (27), and 28 in these two species revealed that the aldehyde oxygens are not retained in the biosynthesis. [Chemical models not reproduced] De novo biosynthesis of the 3-hydroxybutyrate side chain of diaulusterol A (34) in Diaulula sandiegensis was proven by incorporation of [1,2- C2]acetate. None of [1,2- 13C2] acetate, [2-14C] mevalonate, and [4-14C]cholesterol was successfully incorporated in the steroid portion of 34. Synthesis of [2,l'-13C2]disodium 2-ethylmalonate and [2,3-13C2] sodium butyrate followed by injection into the nudibranch Triopha catalinae demonstrated that T. catalinae utilizes butyrate in the processive polyketide biosynthesis of triophamine (43). This represented the first proven use of butyrate in polyketide biosynthesis by a marine invertebrate. [Chemical model not reproduced] Investigation of the extracts of the North Sea flatworm Prostheceraeus vUlatus and its prey, the ascidian Clavelina lepadiformis, revealed the presence of one known and four novel secondary metabolites: the decahydroquinoline alkaloid lepadins A, B, and C and pyrrolidine alkaloid villatamines A and B.P. villatus concentrates the alkaloids from its diet, analogous to the relationship between many shell-less molluscs and their algal or sponge dietary organisms. === Science, Faculty of === Chemistry, Department of === Graduate