Synthesis of 2-ene-1,4-diols by a new cascade-opening of 1,3-diepoxides: towards an efficient synthesis of dihydroxytaxoid derivatives.

Taxing taxanes: A new method for the preparation of alk-2-ene-1,4-diols from 1,3-dienes, especially for geometrical constrained derivatives, via dioxirane derivative formation followed by Ti(III)-induced oxirane ring opening, is described. The strategy has been very efficiently implemented to the construction of the 11-ene-10,13-diol moiety present in taxol derivatives.

cis-Platinum Complex Encapsulated in Self-Assembling Cyclic Peptide Dimers.

A new cyclic peptide dimer that encapsulates cisplatin complexes in its internal cavity is described. The resulting complex showed cytotoxic activity at A2780 ovarian cancer cell lines independent of acquired platinum resistance.

Sequence-specific peptide synthesis by an artificial small-molecule machine.

The ribosome builds proteins by joining together amino acids in an order determined by messenger RNA. Here, we report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence-specific manner. The chemical structure is based on a rotaxane, a molecular ring threaded onto a molecular axle. The ring carries a thiolate group that iteratively removes amino acids in order from the strand and transfers them to a peptide-elongation site through native chemical ligation. The synthesis is demonstrated with ~10(18) molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry.

Toward an efficient synthesis of taxane analogs by dienyne ring-closing metathesis.

An efficient tandem ring-closing dienyne metathesis of dienynes derived from cyclohex-2-enone affords the [5.3.1] carbon framework characteristic of taxanes in a single-step process. Further stereoselective functionalizations of the resulting [5.3.1] carbon framework lead to an advanced intermediate in a novel synthetic strategy for taxane analogs.

Dienyne ring-closing metathesis approach for the construction of taxosteroids.

A cascade dienyne ring-closing metathesis approach has been applied to the synthesis of the tetracyclic carbon framework of a new class of hybrid compounds-the taxosteroids-possessing carbon frameworks incorporating moieties characteristic of both taxanes (such as AB rings) and steroids (i.e., CD system and side chain). This tandem cyclization is highly stereoselective, allowing the one-step formation of the bicyclo[5.3.1]undecene system characteristic of taxol. In this work we describe the scope and limitations of such cyclizations.