Synthetic studies on the tetrahydrofuran containing acetogenins.
Item
-
Title
-
Synthetic studies on the tetrahydrofuran containing acetogenins.
-
Identifier
-
AAI9908356
-
identifier
-
9908356
-
Creator
-
Ruan, Zheming.
-
Contributor
-
Adviser: David R. Mootoo
-
Date
-
1998
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Chemistry, Organic | Chemistry, Pharmaceutical
-
Abstract
-
The tetrahydrofuran (THF) containing acetogenins have attracted interest because of their highly potent and diverse bioactivities. They are new candidates for anticancer agents, based on promising antitumor effects in in vitro as well as in vivo studies. They are C35-C39 compounds which generally contain one or more 2, 5-disubstituted THF's of variable stereochemistry and a {dollar}\alpha ,\beta{dollar}-unsaturated {dollar}\gamma{dollar}-lactone subunit. A number of different synthetic approaches have been published.;Two methods for the preparation of 2,5-disubstituted THF's were previously developed in our laboratory. The first was the synthesis of cis-2,5-disubstituted THF's via the haloetherification reaction of alkenylated monosaccharides. The second was the synthesis of trans-2,5-disubstituted THF's from 5,6-O-isopropylide alkenes.;Based on the first strategy, a highly convergent methodology for adjacently linked bis-THF's containing cis-2,5-disubstituted THF's was developed. Using bis-pyranoside alkenes, in which one of the monosaccharide fragment is equipped with an activated cis directing aglycone (trityl) and the other with a deactivating aglycone (trifluoroethyl), as precursor, 32/64 possible adjacent bis-THF containing acetogenins may be prepared with this methodology. This convergent strategy is especially well suited to polyether structures which do not have highly symmetrical substitution patterns, as found for example in Ionophore A204.;Based on the second strategy, a bi-directional approach to adjacently linked bis-THF's containing trans-2,5-disubstituted THF's was developed. Syntheses of the known trilobacin and asimicin bis-THF cores were accomplished. The use of relatively straightforward and inexpensive reactions should allow these compounds to be prepared on relatively large scales. 16 of the 64 possible bis hydroxymethyl bis-THF cores can be prepared via this strategy. Together both methodologies allows access to 40 of the 64 possible stereoisomers of the bis hydroxymethyl bis-THF cores.;Finally, application of the bidirectional strategy to more complex polycyclic ether structures was tested. The synthesis of a study of simple polyether analog of Kijimicin and monensin, was performed.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
