1. A formal total synthesis of dysiherbaine. 2. Asymmetric total synthesis of ceratopicanol = 1. 디시허베인의 전합성에 관한 연구. 2. 쎄라토피카놀의 입체 선택적 전합성에 관한 연구

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Dysiherbaine and Neodysiherbaine are a novel neurotoxic amino acid isolated from marine sponge Dysidea herbacea by Sasaki in 1997. Pharmacologically, Dysiherbaine is considerably valuable since it was found to be an agonist for glutamate receptors and more potent than domoic acid or kainic acid, so this could be one of major medicinal candidate for epilepsy, Huntington’s disease, and Alzheimer’s diseases. Dysiherbaine / Neodysiherbaine has unique skeletal structure of cis-fused hexahydrofuraopyran ring substituted with alanine amino side chain. By now 6 groups have been researched for synthesis of these compounds and showed difficulties for construction of congested stereocenters at C-4, 6, and 7 position. We designed a new strategy in view of the efficiency for setup these stereocenters utilizing diene metathesis pathway. Exploring the model compound we disclosed this could be the straightforward route, wherein the meta-substituted allyloxy oxabicyclo[2,2,1]heptene was transformed to cis-fused hexahydrofuraopyran structure through Grubb’s ROCM (ring opening-cross metathesis) route. With this satisfactory result we undertook the asymmetric formal synthesis of Dysiherbaine. The enantiopure allyloxy oxabicyclo[2,2,1]heptene structure was synthesized from Diels-Alder reaction between substituted furan and 1,2-trans-bis(phenylsulfonyl) ethylene, and followed by resolution of those diastereomers from O-acetyl-L-mandelic acid. The chirally pure meta-substituted allyloxy oxabicyclo[2,2,1]heptene was subjected to domino metathesis with vinyl acetate and Hoveyda-Grubb’s II catalyst to produce stereocontrolled hexahydrofuropyran core structure of Dysiherbaine and Neodysiherbaine. Side chain manipulation of vinyl acetate and double bond afforded Sasaki’s intermediate for 16 steps, 2.3% overall yield. In 1988, Hanssen and Abraham reported the isolation of a novel triquinane sesquiterpene (+)-Ceratopicanol in agar cultures of the Ascomycete Ceratosystis piceae Ha 4/82, and...
Advisors
Lee, Hee-Yoonresearcher이희윤
Description
한국과학기술원 : 화학과,
Publisher
한국과학기술원
Issue Date
2012
Identifier
512047/325007  / 020085304
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 화학과, 2012.8, [ iv, 154 p ]

Keywords

Metathesis; Dysiherbaine; Diels-Alder; Ceratopicanol; Triquinane; 디시허베인; 메타티시스반응; 딜스알더반응; 쎄라토피카놀; 트리메틸렌메탄; TMM

URI
http://hdl.handle.net/10203/180293
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=512047&flag=dissertation
Appears in Collection
CH-Theses_Ph.D.(박사논문)
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