H. Martin R. Hoffmann

The asymmetric dihydroxylation reaction of early stage and advanced Bryostatin C-ring precursors was evaluated. For homoallylic ethers and alcohols, several AD ligands were investigated including a novel class of quinidine-alkynes.

The development and design of reliable and efficient methods for the construction of chiral building blocks are crucial in modern natural product synthesis. 8-Oxabicyclo[3.2.1]oct-6-en-3-ones are readily accessible scaffolds with defined stereochemical features which have been exploited for non-aldol approaches to the preparation of chiral building blocks. Strategies for their enantioselective synthesis, including asymmetric cycloaddition methods, desymmetrization protocols, and “racemic switch operations”, are presented and evaluated.

Die Entdeckung und das Design von zuverlässigen und effizienten Methoden zum Aufbau chiraler Bausteine spielt in der modernen Naturstoffsynthese eine entscheidende Rolle. 8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one sind leicht zugängliche Gerüste mit definierten stereochemischen Eigenschaften, die in Nicht‐Aldolansätzen zur Herstellung chiraler Bausteine genutzt werden. Strategien zu ihrer enantioselektiven Synthese umfassen Methoden für asymmetrische Cycloadditionen, Desymmetrisierungsprotokolle und “Racemic‐Switch‐Operationen”. Die Ergebnisse dieser Arbeiten werden in diesem Aufsatz präsentiert und eingeschätzt.

The stereoselective synthesis of the masked northern half ofthe antimitotic natural product disorazole A₁ is describedinvol­ving as key step a Z-selectiveWittig olefination of a C1-C11 epoxy aldehyde with a C12-C19phosphonium iodide.

Solvolysis of C9 mesylated cinchonidine 1-OMs and cinchonine 2-OMs in solvent MeOH, EtOH, and CF₃CH₂OH affords ring-expanded 1-azabicyclo[3.2.2]nonanes oxygenated at carbon C3 (“second Cinchona rearrangement”). The newly introduced substituents at C3 and the neighboring quinolyl group Q‘ at C2 adopt quasiequatorial positions. The derived 1-azabicyclo[3.2.2]nonan-3-ones 5 and 6 are easily equilibrated. On contact with MeOD uptake of deuterium takes place at room temperature.

C-glycosides - asymmetric synthesis - bicyclic lactones - solvent effect - anomeric activation

The phorboxazoles A and B are a new class of biologically highly active macrolides. The enantiopure C28-C41 segment containing four stereogenic centers, an E-configurated trisubstituted double bond and the 2,4-difunctionalized oxazole moiety has been prepared in 16 steps in 10% overall yield. The synthesis represents advances in strategy and methodology.