Efforts towards the Total Synthesis of Azaspiracid-3

Azaspiracid, a structurally complex marine toxin isolated from the mussel Mytilus edulis in Killary Harbor, Ireland, represents a new class of marine metabolites unrelated to any previous known agent of diarrhetic shellfish posioning. As such, the natural product has spurred considerable interest among organic community. The thesis details the study towards the total synthesis of azaspiracid-3.The C1-C21 domain and C22-C40 domain have been synthesized, which aims to assemble the molecule through Yamaguchi esterification. The ABCD domain involved an efficient NHK coupling reaction between C1-C12 segment and C13-C22 segment. The trioxadispiroketal skeleton was constructed under the influence of acid catalysis. The EFGHI domain highlighted a chelate controlled Mukaiyama aldol reaction to produce C22-C40 linear precursor, and a DIHMA process to assemble the bridged ketal. With the recognition of bridged ketal and spiroaminal functionality in the FGHI domain, the gold-catalysis to achieve these moieties has been proposed. A novel gold-catalyzed spiroaminal formation has been systemically developed. The gold-catalyzed ketallization was then successfully implemented to construct the bridged ketal, while an inevitable elimination could not deliver the desired spiroaminal under gold conditions. A NHK reaction to couple the C1-C21 and C22-C40 domains has also been proposed. The revised C22-C40 domain was achieved with a similar synthetic route.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Zhang, Zhigao

Contributors dc:contributor

• Forsyth, Craig

• Chemistry

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1366108671

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1366108671