I. Total synthesis and application of fluorophore-labeled didemnin and tamandarin analogues. II. Synthetic approaches to pondaplin and analogues. III. Yohimbanones: Formation and reaction via novel rearrangements

The didemnins are a class of macrocyclic depsipeptides that were isolated from a Caribbean tunicate of the family Didemnidae. Recently, the isolation and characterization of tamandarin A from an unclassified didemnid was reported. While the chemical structure and cellular activity of tamandarin A is comparable to that of didemnin B, the two metabolites have not yet been shown to exhibit a common biochemical and ecological function. The research described herein makes use of fluorescent probes to gain insight into the biological activity of these depsipeptides. Fluorescent didemnin and tamandarin analogs were prepared and were employed in an ecological study to determine the effect of these metabolite analogs on established predator-prey relationships. Pondaplin is a novel cyclic prenylated phenylpropanoid isolated from Annona glabra, which is commonly referred to as pond apple. Research described herein is aimed at developing efficient approaches to structures of this type, which garner interest due to the strain inherent in these molecular architectures. The results of a variety of synthetic strategies are discussed. Additionally, the properties of the pondaplin dimer and trimer are investigated. The yohimbines, members of the Rauwolfia alkaloid family, have attracted a great deal of synthetic interest over the years due to the interesting structures and diverse biological activities of these alkaloids. For some time, it has been known that tryptophan and ninhydrin can be condensed to provide a pentacyclic indole heterocycle bearing a carbon skeleton reminiscent of yohimbane. However, the details of this transformation, including the mechanism, have remained unclear. A simple structural modification has allowed the isolation of a reaction intermediate. This intermediate may be independently converted to the yohimbanone product. We propose a mechanism for this novel rearrangement that is in accord with the known reactivity of ninhydrin. The yohimbanone skeleton has been converted via an oxidative ring opening to a 1-aroyl-β-carboline-3-carboxylate. Compounds of this type have been shown to be antagonists of benzodiazepines in vivo