Synthesis and determination of the absolute configuration of Armatol A through a polyepoxide cyclization cascade : revision of the proposed structures of Armatols A-F

Cyclization Cascades Leading to the Tricyclic Fragment of Armatol A The synthesis of the fused 6,7,7-tricycle of armatol A was investigated. Fragments containing both a ketone and an aldehyde for subsequent fragment coupling were generated via a triepoxide cascade. Elimination of the secondary alcohol in the oxepane ring proved challenging; however, employing the Shapiro reaction successfully provided the desired oxepene. Ketone and aldehyde tricycles were synthesized in 11 and 7 steps, respectively, and both enantiomers of aldehyde fragment were synthesized. These short routes enable the preparation of sufficient quantities of these tricycles for fragment coupling studies. Fragment Coupling, Synthesis, and Determination of the Absolute Configuration of Armatol A A stereoselective synthesis of a bromooxepane ring via a bromonium-initiated epoxide-opening cyclization was explored. Functionalization of the primary alcohol formed from this cascade allowed for a variety of coupling strategies to be explored to form the carbon framework of armatol A. Difficulties reducing a cis alkene adjacent to a tertiary alcohol forced a strategic revision; an analogous trans alkene was easily reduced to form the acyclic alkyl chain connecting the ring-containing fragments of armatol A. Stereoselective installation of the tertiary alcohol allowed for a detailed investigation of the absolute structure of armatol A. At the outset, four diastereomers were consistent with the published data for the natural product. After determining that this tertiary alcohol must be syn to the adjacent THP ring stereocenter, the syntheses of the two remaining possible diastereomers of armatol A were completed. Of the four diastereomers shown in the figure, diastereomer B was confirmed by synthesis to be the correct structure of armatol A. Using this information, structural revisions of the entire family of armatols were proposed, as was a new biogenesis of these natural products. Four possible diastereomers of armatol A based on reported data...

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2011

Author dc:creator

• Underwood, Brian Saxton

Advisor dc:contributor.advisor

• Timothy F. Jamison.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/62729

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/62729