Total synthesis of the marine alkaloid halichlorine: development and use of a general route to chiral piperidines.

The total synthesis of the marine alkaloid halichlorine is described, based on an approach that involves constructing the fully substituted asymmetric center at an early stage. The five-membered ring is formed by 5-exo-trig radical cyclization and the unsaturated six-membered ring by a process that formally represents a sequential combination of conjugate addition and S(N)2' displacement-a method that is general for making bicyclic compounds with nitrogen at a ring fusion position. A formal synthesis of (+)-halichlorine is also reported, based on the development of a general method for preparing optically pure piperidines.

Synthesis of the potent anticancer agents ottelione A and ottelione B in both racemic and natural optically pure forms.

The powerful antitumor agents ottelione A and B were synthesized in racemic form by a method that relies on selective ring closing metathesis. Optically pure natural (+)-ottelione A was then made from d-ribose, via an alpha-keto cyclopropane. A key feature of the route is that the cyclopropyl group controls the stereochemistry in the attachment of the ArCH2 unit and is then converted by the action of SmI2 into a vinyl group, so that the substituents on the resulting five-membered ring have the required trans relationship.

Effect of para-substituents on alkaline earth metal ion extraction by proton di-ionizable calix[4]arene-crown-6 ligands in cone, partial-cone and 1,3-alternate conformations.

Two carboxylic acid or N-(X)sulfonyl carboxamide groups were incorporated into calix[4]arene-crown-6 compounds to afford di-ionizable ligands for use in divalent metal ion separations. Acidities of the N-(X)sulfonyl carboxamide groups were tuned by variation of the electron-withdrawing properties of X. Cone, partial-cone and 1,3-alternate conformations were obtained by different synthetic strategies and their structures verified by NMR spectroscopy.

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 compounds in the cone conformation: synthesis and alkaline earth metal cation extraction.

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 ethers in the cone conformation were prepared and their conformations and regioselectivities were verified by NMR spectroscopy. The metal ion-complexing properties of these ligands were evaluated by competitive solvent extractions of alkaline earth metal cations from water into chloroform. The ligands were found to be efficient extractants with selectivity for Ba(2+).

Formal radical cyclization onto benzene rings: a general method and its use in the synthesis of ent-nocardione A.

An indirect method is described for effecting radical cyclization onto a benzene ring. Cross-conjugated dienones 6, which are readily prepared from phenols, undergo radical cyclization (6 --> 7 --> 8), and the products (8) are easily aromatized. The method has been applied to the synthesis of ent-nocardione A (21).