Studies towards the total synthesis and structural elucidation of leiodolide A

Polyketides;Natural products--Synthesis;Lactones;Chemistry, Organic

Aldred, Gregory ; Florence, Gordon John ; Florence, Gordon John

University:University of St Andrews

Department:Chemistry (School of)

关键词: Polyketides;    Natural products--Synthesis;    Lactones;    Chemistry, Organic;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/6657/GregoryAldred_PhDThesis.pdf?sequence=6&isAllowed=y

来源: DR-NTU

【 摘 要 】

In 2006, the secondary metabolite leiodolide A was isolated from a newly discovered deep-sea sponge of the genus Leiodermatium. The 19-membered macrolide represented a new class of mixed polyketide, nonribosomal, peptide synthetase natural products. A total synthesis of leiodolide A is yet to be achieved and is of specific interest, not only for its complex structure and undefined stereochemistry, but also the potent cytotoxic properties it possesses, particularly towards leukaemia, non-small cell lung and ovarian cancers.A synthetic strategy for leiodolide A must be flexible to overcome the currently unresolved stereochemistry and a convergent route towards the synthesis of the molecule required three subunits. Following the earlier synthesis of the C21-C25 vinyl stannane fragment, this work describes the synthesis of the C1-C10 subunit in the both possible diastereomeric forms. The synthesis of the two required C13 epimers of the C11-C20 subunit is also detailed accompanied by an investigation into potential fragment coupling, in preparation for total synthesis.