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Title: A synthetic approach to (+)-Acutiphycin
Author: Maczka, Maciej
ISNI:       0000 0004 6425 0316
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2017
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(+)-Acutiphycin appeared in the literature in 1984, when Moore and co-workers reported their discovery of this novel macrolide in extracts of the blue-green alga, Oscillatoria acutissima. Their biological evaluations of (+)-acutiphycin subsequently showed efficacy at combatting the growth of a human KB nasopharyngeal cancer cell line during in vitro screening. In addition, it demonstrated significant antineoplastic activity in vivo against murine Lewis lung carcinoma with a T/C of > 150, when administrated at doses of 50 mg/kg, which corresponds to a >50% life extension being conferred on these animals. Due to the significant pharmaceutical interest that exists in (+)-acutiphycin, and in an effort to provide a future clinical supply, there has been significant effort expended on developing a viable total synthesis of this molecule. In Chapter 1 of this thesis I will present synthetic approaches to (+)-acutiphycin published to date in the literature, while Chapter 2 will describe Hale’s approach to this complex molecule. Moreover, I will report the first successful application of O-directed double free radical hydrostannation reaction in the synthesis of natural products. Through an awareness of the highly complex mechanism of this reaction, and our introduction of a conformation-restraining acetal, to prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two trisubstituted alkenes present in the C(7)-C(22) region of (+)-acutiphycin were constructed concurrently with high stereocontrol.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available