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| Research Domain： |
natural products total synthesis, synthetic methods development, and the design and application of new transition metal catalyzed reactions |
| Keyword： |
McIntosh Research Group |
| Research Production： |
Our research group is involved in natural products total synthesis, synthetic methods development, and the design and application of new transition metal catalyzed reactions. The details of some ongoing research research projects are given below. Please see our publications page for details of this work.
Synthetic Approaches to the Eunicellin Diterpenes
The eunicellin diterpenes are a large family of biologically active natural products which have in common a bicyclo[8.4.0]tetradecane ring system, but which differ in stereochemistry and in the degree and pattern of oxidation. Eleutherobin, for example, has been found to have potent anti-cancer activity against a variety of tumor cell lines. It stabilizes microtubules and thus suppresses cell division, a mechanism of action it shares with taxol. Sclerophytin-A exhibits cytotoxicity at 1 ng/ml in the L1210 leukemia cell line. Astrogorgin inhibits cell division in fertilized starfish eggs. Other eunicellin diterpenes such as massileunicellin-I have not been assayed for biological activity. We have embarked on a long term study directed toward the synthesis of several members of the eunicellin diterpene family. The goal is to develop strategies and methods that will result in general and flexible approaches to these targets as well as to simplified analogs. We are exploring two general approaches to the eunicellin diterpenes: the Ireland-Claisen rearrangement and the cycloaldol reaction.
Our research group is involved in natural products total synthesis, synthetic methods development, and the design and application of new transition metal catalyzed reactions. The details of some ongoing research research projects are given below. Please see our publications page for details of this work.
Synthetic Approaches to the Eunicellin Diterpenes
The eunicellin diterpenes are a large family of biologically active natural products which have in common a bicyclo[8.4.0]tetradecane ring system, but which differ in stereochemistry and in the degree and pattern of oxidation. Eleutherobin, for example, has been found to have potent anti-cancer activity against a variety of tumor cell lines. It stabilizes microtubules and thus suppresses cell division, a mechanism of action it shares with taxol. Sclerophytin-A exhibits cytotoxicity at 1 ng/ml in the L1210 leukemia cell line. Astrogorgin inhibits cell division in fertilized starfish eggs. Other eunicellin diterpenes such as massileunicellin-I have not been assayed for biological activity. We have embarked on a long term study directed toward the synthesis of several members of the eunicellin diterpene family. The goal is to develop strategies and methods that will result in general and flexible approaches to these targets as well as to simplified analogs. We are exploring two general approaches to the eunicellin diterpenes: the Ireland-Claisen rearrangement and the cycloaldol reaction.
Most of the eunicellin diterpenes possess a hydroisobenzofuran core with a bridging oxonane ring at C2 and C9. We have found that a novel cycloaldol reaction enables the rapid assembly of the isobenzofuran bicycle with excellent diastereoselectivity. An initial intermolecular aldol reaction between (S)-carvone and methacrolein establishes the desired stereochemistry at C1, C2 and C14. Etherification and cycloaldolization affords the isobenzofuran. The C9 stereocenter is formed with complete diastereoselectivity. Thus four of the stereocenters present in the natural products can be installed in only 3 steps from (S)-carvone. We are employing the cycloaldol reaction in the synthesis of the highly oxidized massileunicellins as well as simplified bicyclic analogs for use in high throughput synthesis. |
| Remarks： |
Matt McIntosh
Associate Professor
101 Chemistry Bldg.,
University of Arkansas,
Fayetteville, AR 72701;
(479) 575-4692 (ph)
(479) 575-4049 (fax)
Website:http://www.uark.edu/campus-resources/mcintosh/mcmgroup.html |
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Promulgator Detail |
| Full name: |
administrator |
| Country: |
CN |
| City: |
Dalian |
| Company Name: |
teloon Soft Strategy Co.,LTD |
| Homepage: |
http://www.hichem.com |
| E-mail: |
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| Phone: |
86-411-82811662 |
| Fax: |
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| Company Address: |
26 Renmin Road ,Dalian China |
| Zip/Postal Code: |
116001 |
| Introduction: |
As a professional E-information service platform with authoritative news and reports in chemical industry of chinese export and import market.Hichem has been received universally and praised highly since its established in 2001.In 2003,by joint effort of teloon chemicals and teloon soft strategy company(TSSC),Hichem team endeavored to recomposition the site ascribed to market requirement as well as offering our better service.Hichem focused on business to biusiness of new chemicals,fine chemicals,high chemicals and special chemicals.So naturally it is the very one-stop website for chemical information.Our sellers worldwide and build global on-line trade in the chemical industry. |
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