Toward a commercial synthesis of (+)-discodermolide.

In this review some of the criteria required for a viable chemical (+)-discodermolide production process are discussed by critical evaluation of the available literature approaches. A further route involving the use of polyketide synthase to produce (+)-discodermolide fragments by fermentation is also described. Both approaches have advantages and disadvantages and require significant optimization in order to achieve commercialization of this important natural product.

Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide: preparation and biological activity.

A series of seven synthetic discodermolide analogues 2-8, which are minor side products generated during the final stages in the synthesis of (+)-discodermolide (1), have been purified and evaluated for in vitro cytotoxicity against A549, P388, MFC-7, NCI/ADR, PANC-1, and VERO cell lines. These synthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 hydroxy through C-17 hydroxy molecular fragment for potency. Specifically, these analogues suggested the relevance of the C-11 hydroxyl group, the C-13 double bond, and the C-16 (S) stereochemistry for the potency of (+)-discodermolide.

Ligands for expression cloning and isolation of GABA(B) receptors.

The scope of the plenary lecture at the occasion of the Xth Meeting on Heterocyclic Structures in Medicinal Chemistry, Palermo 2002, is considerably larger than that of the main lecture at the XVIth International Symposium on Medicinal Chemistry, Bologna 2000, described by Froestl et al. in Farmaco 56 (2001) 101. Additional information is presented, in particular, on the reaction conditions for the 31 step synthesis of the combined affinity chromatography and photoaffinity radioligand [125I]CGP84963 and on the recent developments of the molecular biology of GABA(B) receptors.