Towards 20,20-difluorinated bryostatin: synthesis and biological evaluation of C17,C27-fragments.

Bryostatins with modified C17-C27 fragments have not been widely studied. The synthesis of 20,20-difluorinated analogues was therefore investigated. Such substitution would inhibit dehydration involving the C19-hydroxyl group and stabilise the ring-closed hemiacetal tautomers.

Tying a Molecular Overhand Knot of Single Handedness and Asymmetric Catalysis with the Corresponding Pseudo-D-Symmetric Trefoil Knot.

We report the stereoselective synthesis of a left-handed trefoil knot from a tris(2,6-pyridinedicarboxamide) oligomer with six chiral centers using a lanthanide(III) ion template. The oligomer folds around the lanthanide ion to form an overhand knot complex of single handedness. Subsequent joining of the overhand knot end groups by ring-closing olefin metathesis affords a single enantiomer of the trefoil knot in 90% yield.

Goldberg Active Template Synthesis of a [2]Rotaxane Ligand for Asymmetric Transition-Metal Catalysis.

We report on the active template synthesis of a [2]rotaxane through a Goldberg copper-catalyzed C-N bond forming reaction. A C2-symmetric cyclohexyldiamine macrocycle directs the assembly of the rotaxane, which can subsequently serve as a ligand for enantioselective nickel-catalyzed conjugate addition reactions. Rotaxanes are a previously unexplored ligand architecture for asymmetric catalysis.

Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines.

A versatile synthesis of enantiomerically pure cis- and trans-2,5-disubstituted morpholines is described. Hydroxynitrile lyase-mediated cyanide addition onto aldehydes provided cyanohydrins in virtually quantitative yield and excellent enantioselectivity. Subsequent formation of diastereomerically pure amino esters via a three-step, one-pot reduction-transimination-reduction sequence followed by reduction and simultaneous protection provided cyclization precursors.