Annojahnin from Annona jahnii: a possible precursor of mono-tetrahydrofuran acetogenins.
A new cytotoxic Annonaceous acetogenin, annojahnin (1), was isolated from the twigs of Annona jahnii (Annonaceae) by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C-37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings, bearing a keto group at C-10, and possessing a double bond located two methylenes away from a vicinal diol. The structure and absolute configuration of 1 were elucidated by 1H and 13C NMR, COSY, and single-relayed COSY and from chemical derivatives. 4-Deoxy-18/21-trans-annomontacin 10-one (4) and 4-deoxy-18/21-cis-annomontacin-10-one (5), two semisynthetic mono-THF acetogenins, were prepared from 1 by reactions that mimic the biogenetic pathways. These acetogenins showed selective cytotoxicities, comparable or superior to adriamycin, among six human solid tumor cell lines. Reduction of the 10-keto of 1, to the racemic 10-OH derivative (3), retained the bioactivities as did the conversion of 1 to 4 and 5.
Colman-Saizarbitoria
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Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela.
Johnson
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Alali
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Hopp
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Rogers
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McLaughlin
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JL
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005663:Furans / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods; D010944:Plants / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D005233:Fatty Alcohols; D005663:Furans; D007783:Lactones; C116552:annojahnin; C112079:isomurisolenin; D015107:4-Butyrolactone