Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin.

Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Research Abstract Details 

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Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Abstract Text:

Tonika Chatterji,Murat Kizil,Kripa Keerthi,Goutam Chowdhury, ,Kent S Gates,

Reaction of the antitumor agent leinamycin with cellular thiols results in conversion of the natural product to a DNA-alkylating episulfonium alkylating agent via an intriguing sequence of chemical reactions. To establish whether the chemistry first seen in leinamycin represents a general motif that can function in various molecular frameworks, construction of greatly simplified analogues containing only the "core" funcional groups anticipated to be necessary for thiol-triggered generation of an alkylating agent was undertaken. For this purpose, the "stripped-down" leinamycin analogue 7-(3-methyl-but-2-enyl)-1-oxo-1H-lambda4-benzo[1,2]dithiol-3-one (4) was synthesized. Treatment of 4 with thiol under several different conditions results in efficient conversion of the compound to cyclized 2,3-dihydro-benzo[b]thiophene-7-carboxylic acid products (13) that are envisioned to arise from Markovnikov addition of solvent to an intermediate episulfonium ion (14). Thus, the relatively simple molecule 4 is able to mimic the thiol-triggered alkylating properties displayed by the natural product leinamycin. This work helps define why the core functional groups required thiol-accelerated generation of an alkylating intermediate from leinamycin and indicates that substantially altered analogues of the natural product may retain alkylating properties. In a broader context, the results provide evidence that the unique cascade of chemical reactions first seen in the context of leinamycin represents a general motif that can operate in a variety of molecular frameworks.

Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Publishing Authors By Initials

T Chatterji,M Kizil,K Keerthi,G Chowdhury,T ,KS Gates,

For similar thiones research abstracts see: thiones research

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Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 125

Page Numbers: 4996-7

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 30

MONTH: Apr

YEAR: 2003

Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Keywords Mesh Terms:

KEYWORDS: Thiones

MESH TERMS: chemistry

Chemical & Substance for Abstract: Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin. Information

Substance Name: leinamycin

Registry Number: 120500-15-4

Grant and Affiliation Information for Small molecules that mimic the thiol-triggered alkylating properties seen in the natural product leinamycin.

AFFILIATION: Department of Chemistry, University of Missouri, Columbia, Missouri 65211, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA83925

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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