Cooperative ratiometric chemosensors: pinwheel receptors with an integrated fluorescence system.

The synthesis and fluorescent properties of a second generation cooperative chemical sensor are described. The sensor has two interacting binding pockets for cooperative recognition of two analytes. Cooperative binding activates a ratiometric fluorescent response via formation of an excimer. Binding was characterized by NMR, absorption, and fluorescence spectroscopy. The advantages of separating the recognition elements from the fluorescent response elements are discussed.

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.

Naphthalene-based calixarenes: unusual regiochemistry of a Friedel-Crafts alkylation.

[reaction: see text] In the pursuit of naphthalene-based calixarenes, a Friedel-Crafts alkylation with unusual regiochemistry was observed. Treatment of carbinol 14 with catalytic triflic acid was expected to produce calixarenes of the class represented by 16. Instead, the major product was cyclic trimer 15, in which alkylation of each naphthalene ring occurred at the electronically deactivated position. The structure of compound 15 was assigned by 2-D NMR studies.

Bioactive compounds from Combretum erythrophyllum.

A methanol extract of Combretum erythrophyllum showed inhibitory bioactivities in a yeast-based microtiter assay for DNA-damaging agents. Bioassay-guided fractionation of this extract yielded two known bioactive compounds, combretastatin A-1 and (-)-combretastatin, and two new bioactive glucosides, combretastatin A-1 2'-beta-D-glucoside (1) and combretastatin B-1 2'-beta-D-glucoside (2). The structures of the new compounds were assigned by (1)H and (13)C NMR, DEPT, HMQC, and HMBC spectra.

Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest.

The preservation of tropical rainforests is an important goal both for the intrinsic value of their cultural and biological diversity as well as for the well-being of the peoples who make these forests their home. In addition, tropical forests are potential sources of new pharmaceutical products that can only be found by chemical prospecting in Nature's genetically encoded combinatorial library. As part of an effort to integrate biodiversity conservation and drug discovery with economic development, we have initiated a collaborative program to discover potential pharmaceuticals in the rainforest of Suriname. The plant Renealmia alpinia (Zingiberaceae) was selected for investigation based on its ethnomedical use as a febrifuge, but testing in the yeast Sc-7 assay gave a positive response, indicative of cytotoxic activity. Using this bioassay, the two new labdane diterpense, 11-hydroxy-8(17),12(E)-labdadien-15,-16-dial 11,15-hemiacetal (1) and 16-oxo-8(17),12(E)-labdadien-15-oic acid (2), and the known diterpene, 8(17),12(E)-labdadien-15,16-dial (3), have been isolated. Their structures were elucidated by 1D and 2D NMR techniques (DEPT, COSY, HETCOR, HMBC, and NOESY) and IR, UV, and MS spectra, and the absolute stereochemistry of 1 was established by CD spectroscopy and by the formation and NMR analysis of alpha-methoxyphenylacetyl esters. The hemiacetal 1 was cytotoxic to M109 cells, with an IC50 value of 2.6 micrograms/mL.

New norcucurbitacin and heptanorcucurbitacin glucosides from Fevillea trilobata.

From the MeOH extract of the seeds of Fevillea trilobata (Cucurbitaceae) were isolated fevicordin A glucoside [1], cayaponoside B [2], cayaponoside D [3], a new norcucurbitacin glucoside, and a new heptanorcucurbitacin glucoside. The structure of the new norcucurbitacin glucoside, andirobicin A glucoside, was established as 29-nor-1,2,3,4,5,10-dehydro-25-methoxy-2-O-beta-D-glucopyranosyl- 3,16 alpha,20R,22 xi-tetrahydroxy-11-oxocucurbit-23-ene [4], and that of the novel heptanorcucurbitacin glucoside, andirobicin B glucoside, as 22,23,24,25,26,27,29-heptanor-1,2,3,4,5,10-dehydro-2-O-beta-D-g luc opyranosyl-3,16 alpha-dihydroxycucurbita-11,20-dione [5].

Bioactive furanonaphthoquinones from Crescentia cujete.

Bioassay-directed fractionation of the MeCOEt extract of Crescentia cujete (Bignonaceae) resulted in the isolation of (2S,3S)-3-hydroxy-5,6-dimethoxydehydroiso-alpha-lapachone [1], (2R)-5,6-dimethoxydehydroiso-alpha-lapachone [2], (2R)-5-methoxydehydroiso-alpha-lapachone [3], 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [4], 5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [5], 2-isopropenylnaphtho[2,3-b]furan-4,9-dione [6], and 5-hydroxydehydroiso-alpha-lapachone [7]. Compounds 1-3 are new, and all compounds are bioactive, showing selective activity towards DNA-repair-deficient yeast mutants. The isolation, structure elucidation, and biological activities of these compounds are reported.

Bioactive and other sesquiterpenoids from Porella cordeana.

Bioassay-directed fractionation of the MeCOEt extract of Porella cordeana yielded drimenin [1] and aristolone [4], which were moderately toxic towards DNA-repair-deficient mutants of Saccharomyces cerevisiae. Three inactive sesquiterpenes, 7-ketoisodrimenin [2], 7-ketoisodrimenin-5-ene [3], and norpinguisanolide, were also obtained. Compounds 2 and 3 are new.