John F. Kozlowski

Muricatacin: A simple biologically active acetogenin derivative from the seeds of annona muricata (annonaceae)

A biologically active constituent, bearing similarities to the annonacin group of Annonaceous acetogenins, has been isolated from the seeds of Annona muricata. The absolute configuration about the tetrahydrofuran ring of annonacin, which was also isolated, is proposed.

Gonioheptolides A and B: Novel eight-membered-ring lactones from Goniothalamus giganteus (Annonaceae)

Two novel eight-membered-ring lactones, gonioheptolides A (1 and B (3), have been isolated from the bark of Goniothalamus giganteus. The structures were elucidated by IR, MS, 1H and 13C NMR, COSY, HMQC, HMBC, and NOESY spectra. 1 and 3 showed marginal cytotoxicities to certain human solid tumor cells in culture. A biogenetic pathway of the 14 styryllactones found in G. giganteus is proposed.

The absolute configuration of trilobacin and trilobin, a novel highly potent acetogenin from the stem bark of Asimina triloba (Annonaceae)

Abstract Trilobacin ( 1 ) is the only previously reported Annonaceous acetogenin with the erythro relative configuration between the adjacent bis-tetrahydrofuran (THF) rings. The relative configuration in the adjacent bis-THF moiety of 1 was corrected to threo/trans/erythro/cis/threo from C-15 to C-24, and the absolute configuration was determined as 4 R , 15 R , 16 R , 19 R , 20 S , 23 R , 24 R and 36 S by advanced Mosher ester methodology and the COSY and NOESY spectral analyses of its 4,24-diacetate ( 1a ). Further investigation of the EtOH extract of the stem bark of the paw paw tree, Asimina triloba , monitoring for bioactivity by brine shrimp lethality, led to a novel acetogenin, trilobin ( 2 ). Spectral and chemical methods identified 2 as a 4-deoxy-10-hydroxy isomer of 1 . The absolute configuration of 2 was determined as 10 R , 15 R , 16 R , 19 R , 20 S , 23 R , 24 R , and 36 S by analyses of its Mosher ester derivatives. 2 was selectively cytotoxic among three human solid tumor cell lines with over a billion times the potency of adriamycin.

Reticulatacin: A new bioactive acetogenin from Annona reticulata (Annonaceae)

Abstract A new bioactive monotetrahydrofuran acetogenin, reticulatacin, containing 37 carbons, has been isolated from a 95% EtOH extract of the bark of A. reticulata by directing the fractionation with brine shrimp lethality. Another previously reported highly potent antitumor, adjacent ring bistetrahydrofuran acetogenin, bullatacin, has also been isolated in large quantity. Two known diterpenes, (−)-kau-16-en-19-oic acid and methyl 16β,17-dihydro-(−)-kauran-19-oate and a known alkaloid, liriodenine, have also been isolated. Some of these compounds showed selective cytotoxic activities for certain human tumor cell lines.

Novel cytotoxic annonaceous acetogenins: (2,4-cis and trans)-bulladecinones from annona bullata (annonaceae)

Abstract A mixture of two novel cytotoxic adjacent bis-tetrahydrofuran (THF) ketolactone acetogenins, (2,4- cis and trans )-bulladecinones ( 1 and 2 ), was isolated from the bark of Annona bullata Rich. (Annonaceae). Adjacent bis-THF rings, located at C-12 and C-16 and having only one adjacent hydroxyl group, and the presence of an erythro vicinal diol in 1 and 2 are new features for the Annonaceous acetogenins.

Novel 6,7-seco-6,11-cyclolabdane diterpenes from cluytia richardiana

Abstract Two novel 6,7-seco-6,11-cyclolabdane diterpenoids, richardianidin-1 and 2, were isolated from the leaves of Cluytia richardiana L. The structure and stereochemistry of 1 and 2 were established to be 6- (acetyloxy)-15,16-epoxy-2,12-dihydroxy-6,7-seco-6,11-cyclolabda-8,13(16),14-triene-7,18-dioic acid γ-lactone δ-lactone and 6-(acetyloxy)-15,16-epoxy-1,12-dihydroxy-6,7-seco-6,11-cyclolabda-8,13(16),14-triene-7,18-dioic acid di-δ-lactone based on spectroscopy and X-ray data.