title: Synthesis and antitumor activity of C-9 epimers of the tetrahydrofuran containing acetogenin 4-deoxyannoreticuin.
abstract: A highly convergent synthesis of mono-tetrahydrofuran (THF) containing acetogenins, that is based on the cross-metathesis of THF and butenolide alkene precursors, was developed. This methodology was applied to the epimers of the C-9 alcohol of 4-deoxyannoreticuin, in an attempt to assign the configuration at this position in the naturally occurring material. Unfortunately, identification of one or the other epimeric structures with the natural product was not possible because of the closeness of the physical data for all three compounds. Both C-9 epimeric analogues showed similar cytotoxicity in the low micromolar range, against two human tumor cell lines PC-3 (prostate) and Jurkat (T-cell leukemia). This result contrasts to previous studies on closely related THF acetogenins, wherein configurational variation at analogous carbinol centers resulted in a significant effect on antitumor activity.
authors.affiliation: Department of Chemistry, Hunter College, 695 Park Avenue, New York, NY 10065, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Akira
authors.initials: A
authors.lastname: Kawamura
authors.forename: David R
authors.initials: DR
authors.lastname: Mootoo
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000473:pathology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D054378:Acetogenins; D000970:Antineoplastic Agents; D005663:Furans; C018674:tetrahydrofuran
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