The work presented in this thesis describes the synthesis of labd-13-en-8ß, 15-diol (46) a stable reduced derivative of an unstable marine natural product aldehyde [8ß-hydroxylabd-13E-en-15-al (6)] isolated by Cimino, et al. from the skin of a Notaspidean mollusc Pleurobranchaea meckelii. The rationale for the synthesis was to provide sufficient 46 for eventual mild oxidation to 6 and investigation of the biological activity of this latter compound. (-)-Sclareol (32), a common diterpene synthetic precursor, was the starting point for the ten step synthesis of 46 described in this thesis. A search of the literature revealed that only one non stereospecific synthesis of 46 had been previously reported. To provide the necessary background to the synthetic component of this thesis, both the occurrence of labdane and ent-labdane in the marine environment and the use of sclareol in the synthesis of marine natural products, was reviewed. The initial step in the synthesis of 46 was the potassium permanganate oxidation of sclareol to give a bisnorlabdane ketone. Reduction of this ketone with lithium aluminium hydride produced a mixture of diols which, through t-butyldimethysilyl triflate protection, afforded a quantitative route to protecting the C-13 ketone in an effort to prevent unwanted intramolecular cyclization reactions. Dehydration of the tertiary alcohol moiety at C-8 with phosphorous oxychloride yielded the Δ⁸·¹⁵ exocyclic alkene required for the next oxidation step. Ozonolysis succeeded in producing the desired C-8 ketone after much deliberation and research into alternative oxidation strategies. Methyl lithium methylation quantitatively afforded the desired a-methyl substitution at C-8, identified at the onset as the key step in the synthesis. Tetra-butylarnmonium fluoride deprotection yielded the 8ß,13-dihydoxylated product, which was in turn subjected to a Swern oxidition to give the desired 8ß-hydroxy-bisnorlabda-13-one. A modified Horner-Wadsworth-Emmons reaction allowed for elaboration at C-13 to yield a to Δ¹³ olefin with a terminal C-15 ethyl ester. Diisobutylaluminium hydride reduction of the ester produced the desired labd-13-en-8ß, 15-diol (46) in a low overall yield of 3.4%. Although opportunities for optimization of at least three steps in the synthesis exist, time constraints prevented both optimization of these steps and an investigation of the oxidation of 46 to 6. / KMBT_363 / Adobe Acrobat 9.54 Paper Capture Plug-in

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Dong, Jiaqiang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 169-186). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

*Please refer to dissertation for diagrams. / Chapter 2 is concerned with the aim of our research work, retrosynthetic analysis and strategy. Herein, we report the synthesis of the pivotal precursor aldehyde (112) by a Grob fragmentation procedure. In addition, model studies of the key biomimetic aldol cyclization are also discussed. We completed the total synthesis of the two novel diterpenes (+/-)-( 1) and (+/-)-(2) via intramolecular Michael reaction and alpha-ethylidenation starting from (+/-)-Wieland-Miescher ketone. / In Chapter 1, an overview of the isolation, structure elucidation and bioactivities of pallavicinin (1) and neopallavicinin ( 2) are presented. In addition, various synthetic approaches toward the analogous skeletons of the two novel diterpenes are reviewed. / In Chapter 3, a brief conclusion is provided.* / Two novel diterpenes, named pallavicinin (1)and neopallavicinin (2)were first isolated from liverwort Pallavicinia subciliata by Wu16 and their coworkers in 1994. These compounds show potential bioactivities, such as antipyretic properties, muscle regeneration and detoxification.17,18 The diverse structural features of these novel diterpenes in conjunction with their potential bioactivities have stimulated our considerable interest in the quest for their total synthesis. / Peng Xiahshui. / "April 2006." / Adviser: Henry N. C. Wong. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6412. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 186-200).

Thesis (M.S.)--Villanova University, 2009. / Chemistry Dept. Includes bibliographical references.

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