Recent biomimetic and organocatalytic syntheses of α-tocopherol

We report here on our efforts to develop new strategies for the synthesis of α-tocopherol, the biologically most significant member of the vitamin E family. This review comprises five new methods to generate the chiral chromane of α-tocopherol with overall up to 29% yield from commercially available material and up to 94% de

Biomimetic chromanol cyclisation : a common route to to α-Tocotrienol and α-Tocopherol

A common synthetic route to alpha-tocotrienol and alpha-tocopherol has been accomplished by a biomimetic cyclization that yields the chromanol ring.  The chirality at C2 of the chromanol was induced by a covalently attached chiral dipeptide.  Its terminal Asp participates in the enantioface-selective protonation of the double bond of the alpha-tocotrienol precursor I.  alpha-Tocotrienol was diastereoselectively hydrogenated to alpha-tocopherol

A short route to alpha -tocopherol

A simple and practical route to alpha-tocopherol (I) is described.  The key step is a remarkably diastereoselective domino aldol/oxa-Michael reaction, which is promoted by a proline deriv

Modular ligands for dirhodium complexes facilitate catalyst customization

Although stereoselectivity is often the focus of ligand optimizations in catalysis, ligand modularity can be used to control many other properties of catalysts. For example, solubility, amenability to purification, and steric shielding of sensitive catalytic intermediates are all important, but seldom appreciated, functions of ligands. We describe a brief and modular approach to various homo- and heteroleptic lantern-type rhodium(II) complexes and perform benchmarking studies with the new catalysts in common rhodium(II)-catalyzed reactions. We demonstrate the power of ligand modularity by creating catalysts customized for aqueous catalysis or for applications in chemical biology

Diastereoselective synthesis of alpha -tocopherol : a new concept for the formation of chromanols

A diastereoselective synthesis of alpha-tocopherol (93% de) was achieved via two key steps, (i) a highly diastereoselective Shi epoxidn. of trisubstituted alkene I and (ii) an acid supported, "anti-Baldwin" epoxide ring opening under inversion of configuration leading to the 6-membered chromanol ring

Asymmetric Synthesis of alpha -Tocopherol

alpha-Tocopherol was synthesized from a chiral intermediate alpha-hydroxy ester by means of two ring-closing methods to yield the chromanol in 94 % diastereomeric excess

Fluorescent probes for rapid screening of potential drug-drug interactions at the CYP3A4 level

Steroid derivs. bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized.  For example, reacting testosterone deriv. I with deazaflavinyl alc. II gave ester III.  These compds. are unique inhibitors of cytochrome P 450 3A4 (CYP3A4) and display similar IC50 values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipine.  On binding to CYP3A4, the fluorescence of the dansyl, deazaflavin, and pyrene probes is quenched by photophys. interaction of the fluorophore with the heme.  The addn. of drug candidates with binding consts. in the nM-microM range causes displacement of the probes from the active site, and hence leads to restoration of fluorescence.  Accordingly, relative affinities of drug candidates to CYP3A4 can be easily and accurately detd. by fluorescence measurements

Bioorganic and bioinorganic chemistry

The interdisciplinary projects in bioinorganic and bioorganic chemistry of the Department of Chemistry, University of Basel led to the preparation of new systems that mimic biologically important processes and to the discovery of compounds from natural sources which are very promising with respect to medical applications. The advances in these areas are reported here

Diastereoselective and Highly Enantioselective Henry Reactions using C(1)-Symmetrical Copper(II) Complexes

Catalytic Henry reactions of aliphatic aldehydes and prochiral nitro compounds were investigated using copper(II) complexes of 14 C(1)-symmetrical ligands derived from (1R,2R)(-)-diaminocyclohexane. beta-Nitro alcohols with syn:anti ratios of up to 5.7 and excellent ee values for both diastereosimers were obtained