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Isolation, structure determination, and biosynthetic studies of secondary metabolites from Dorid Nudibranchs

University of British Columbia

Investigations of the skin extracts from a number of dorid nudibranchs have led to the isolation of two novel compounds, lovenone (2) and limaciamine (8). Lovenone (2), isolated from the North Sea dorid Adalaria loveni, represents the first triterpenoid isolated from a nudibranch, and is only the second triterpenoid ever isolated from a marine mollusc. The structure of lovenone (2) was solved using a number of two-dimensional NMR techniques. Similarly, the isolation of limaciamine (8) from the North Sea dorid Limacia clavigera, represents the only naturally occurring analogue reported to date of triophamine (9). Triophamine (9) was originally isolated from the British Columbia dorids, Triopha catalinae and Polycera tricolor. [Model omitted] The isolation and structure determination of these novel compounds led directly to an investigation into the biosynthesis of secondary metabolites by dorid nudibranchs. By taking advantage of the unique biology of dorid nudibranchs, a protocol has been developed whereby multiple injections over time of [1,2-¹³C₂] acetate has afforded irrefutable proof for de novo biosynthesis in a number of dorid nudibranchs. Terpenoic acid glycerides have been isolated from skin extracts of a number of dorid nudibranchs collected worldwide. Herein is reported the first unambiguous proof for the de novo synthesis of terpenoic acid glycerides 28 and 29, isolated from Archidoris odhneri and A. montereyensis, respectively, by NMR analysis of ¹³C-¹³C coupling arising from incorporation of intact doubly labeled acetate. [Model omitted] Stable isotope incorporation studies with [1,2-¹³C₂] acetate have been used to investigate the biosynthesis of the sesquiterpenoids nanaimoal (38), acanthodoral (39), and isoacanthodoral (40) by the dorid nudibranch Acanthodoris nanaimoensis. The results have shown that: i) the sesquiterpenoids are synthesized de novo by A. nanaimoensis and ii) that a previously proposed biogenetic pathway to the isoacanthodoral skeleton was not tenable and required modification. [Model omitted] The use of stable isotope methodology has been extended to probe polyketide biosynthesis by the dorid nudibranch, Triopha catalinae. Incorporation of [1,2-¹³C₂]acetate into triophamine (9) has clearly shown the biogenesis of (9) from two units of butyrate and one unit of acetate. This work represents the first experimental evidence for de novo polyketide biosynthesis by a dorid nudibranch; moreover, the use of doubly-labeled [1,2-¹³C₂] acetate has provided clear evidence in support of one pathway where a number of biosynthetic pathways were possible.

Thesis/Dissertation

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2009-03-16

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http://hdl.handle.net/2429/6090

Chemistry

University of British Columbia

UBCV

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