Synthesis of triazole-fused tetracyclic spirooxindole derivatives via metal-free Huisgen cycloaddition.

We report an efficient, metal free method for synthesizing tetracyclic spirooxindole derivatives from N-protected isatins and propargyl bromide via Huisgen cycloaddition. This simple and practicle method provides access to spirooxindoles containing five-, six-, or seven-membered rings fused to a triazole ring.

Biocatalytic dynamic kinetic reductive resolution with ketoreductase from Klebsiella pneumoniae: the asymmetric synthesis of functionalized tetrahydropyrans.

Ketoreductase from growing cells of Klebsiella pneumoniae (NBRC 3319) acts as an efficient reagent for converting racemic α-benzyl/cinnamyl substituted-ß-ketoesters to the corresponding ß-hydroxy esters with excellent yields and stereoselectivities (ee and de >99 %). The reactions described herein followed a biocatalytic dynamic kinetic reductive resolution (DKRR) pathway, which is reported for the first time with such substrates. It was found that the enzyme system can accept substituted mono-aryl rings with different electronic natures. In addition, it also accepts a substituted naphthyl ring and heteroaryl ring in the α-position of the parent ß-ketoester. The synthesized enantiopure ß-hydroxy esters were then synthetically manipulated to valuable tetrahydropyran building blocks.

A distinctive transformation based diversity oriented synthesis of small ring carbocycles and heterocycles from biocatalytically derived enantiopure α-substituted-ß-hydroxyesters.

A series of structurally novel small ring carbocyclic and heterocyclic molecules were accessed in an enantiopure fashion. The starting materials, α-substituted-ß-hydroxyesters, were achieved through the biocatalytic dynamic kinetic resolution of parent ß-ketoesters in an excellent enantio and diastereocontrolled way. The active functional groups present in the starting precursor, were then tuned sequentially through certain key transformations (functional group interconversions; FGIs) to yield several small molecular scaffolds in a diverse way. Specific transformations such as halocyclization, ene-yne metathesis, dipolar cycloaddition, Mitsunobu cyclization, ring closing metathesis and Pauson-Khand reactions were mainly applied to generate the diversity.