Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.

The total synthesis of the naturally occurring antibiotic GE81112A, a densely functionalized tetrapeptide, is reported. Comparison of spectral data with those of the natural product and the lack of biological activity of the synthesized compound led us to revise the published configuration of the 3-hydroxypipecolic acid moiety. This hypothesis was fully validated by the synthesis of the corresponding epimer.

Here we report the development of the first enantioselective Dakin-West reaction, yielding a-acetamido methylketones with up to 58 %eewith good yields.T wo of the obtained products were recrystallized once to achieve up to 84 %ee. The employed methylimidazole-containing oligopeptides catalyze both the acetylation of the azlactone intermediate and the terminal enantioselective decarboxylative protonation. We propose ad ispersion-controlled reaction path that determines the asymmetric reprotonation of the intermediate enolate after the decarboxylation.Even though the Dakin-West (DW) reaction dates back to 1928, [1] it is still one of the most effective synthetic procedures to prepare a-acylamido ketones from primary a-amino acids. [2] Generally,t he treatment of an amino acid with an acid anhydride and base,t ypically pyridine,a te levated temperature provides the desired product upon liberation of CO 2 (Scheme 1). Numerous modifications of the original reaction conditions were developed, [2] including catalytic variants, [3] broadening its scope and applicability.U nsurprisingly,the DW reaction found application in the preparation of a-acylamido ketones as valuable precursors for various biologically active compounds, [4] and even in Woodwards fundamental total synthesis of strychnine. [5] Remarkably,n o asymmetric variant has been developed to date,thus restricting the use of this important reaction in modern synthetic chemistry.

All four possible stereoisomers of the natural product (−)-avicennone C were synthesized using two different methods for ring closure. The absolute stereochemistry was elucidated unambiguously by comparison of the analytical data with those of the reported natural product and by single X-ray crystal diffraction of synthetic intermediates. The proposed structure needed to be revised with regard to the absolute configuration of the stereogenic center bearing the secondary hydroxyl group. The reported synthesis offers a flexible, selective, and efficient access to all possible stereoisomers and may be of value for the stereoselective synthesis of other epoxyquinone natural products.

TEMPO was immobilized on continuous-flow-optimized mesoporous silica particles and a TEMPO/DAIB mediated oxidation followed by Knoevenagel condensation was investigated.