Structures of the Didemnins (Antiviral, Antitumor, Compounds)
Gloer, James Benton
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Permalink
https://hdl.handle.net/2142/70229
Description
Title
Structures of the Didemnins (Antiviral, Antitumor, Compounds)
Author(s)
Gloer, James Benton
Issue Date
1983
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Abstract
The didemnins (shown below), promising new antiviral and antitumor depsipeptides, have been isolated from a Caribbean tunicate. Their amino acid compositions were ascertained by gas chromatography/mass spectrometry of the trifluoroacetyl n-butyl ester derivatives of the amino acids present in the total acid hydrolyzates. The identities of non-amino acyl components were revealed by ('1)H NMR spectroscopy and/or by their isolation. The connectivities of the didemnins were elucidated by high resolution field desorption mass spectrometry (HRFDMS) of partial hydrolyzates and by high resolution electron impact mass spectrometry (HREIMS) of the intact depsipeptides. Their structures were later confirmed by high resolution fast atom bombardment mass spectrometry (HRFABMS) of degradation products and of the intact depsipeptides. The sequences of didemnins D and E were determined by FABMS, supplemented by HRFABMS and by analogy to the structures of didemnins A-C. Didemnin A, the simplest of these closely related compounds, contains one mole each of N-methyl-D-leucine (MeLeu), L-threonine (Thr), 3S,4R-statine (Sta), L-leucine (Leu), L-proline (Pro), and N,O-dimethyl-L-tyrosine (Me(,2)Tyr), and a 2R,4R-hydroxyisovalerylpropionyl (Hip) group. Didemnins B-E differ from didemnin A by acylation of the methylamino group of MeLeu with the substitutents shown. Didemnin B is the most active of these compounds, possessing ID(,50) = 0.0022 (mu)g/mL vs. L1210 leukemic cells, T/C up to 199 vs. P388 leukemia, and T/C up to 160 vs. B16 melanoma.
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