Multigram Synthesis of 3,3-Spiro-α-prolines.

A series of novel spirocyclic α-proline building blocks with a spiro conjunction in position 3 of the pyrrolidine ring was prepared to employ two convenient and practical synthetic approaches. Both alternative routes utilize simple and readily available starting materials─cyclic ketones and esters─and comprise 6 and 7 steps, respectively. The methodologies feature distinct advantages, using routine organic chemistry transformations, and are suitable for producing multigram amounts of the target prolines.

Structural Insight on the Selectivity of Calyx[4]Arene-Based Inhibitors of MgDependent Atp-Hydrolases.

Located in plasma membranes, ATP hydrolases are involved in several dynamic transport processes, helping to control the movement of ions across cell membranes. ATP hydrolase acts as a transport protein, converting energy from ATP hydrolysis into transport molecules against their concentration gradients. In addition to energy metabolism and active transport, ATP hydrolase is essential for maintaining cellular homeostasis and cell function.

4-Azaspiro[2.3]hexane, an Overlooked Piperidine Isostere: Multigram Synthesis and Physicochemical and Structural Evaluation.

An expedient approach to the synthesis of 4-azaspiro[2.3]hexane derivatives is described. The synthetic scheme consists of Tebbe olefination of -Boc-protected 2-azetidinone (including the first use of the deuterated Petasis reagent CpTi(CD) in the building block preparation) and cyclopropanation of the resulting intermediate.

Parallel Minisci Reaction of -Difluorocycloalkyl Building Blocks.

Parallel Minisci reactions of nonfluorinated and -difluorinated C-C cycloalkyl building blocks (trifluoroborates and carboxylic acids) with a series of electron-deficient heterocycles were studied. A comparison of the reaction's outcome revealed better product yields in the case of carboxylic acids as the radical precursors in most cases, albeit these reagents were used with three-fold excess under optimized conditions. The nature of the heterocyclic core was found to be important for successful incorporation of the cycloalkyl fragment.

3-Substituted 6-Azabicyclo[3.1.1]heptanes: Nonclassical Piperidine Isosteres for Drug Discovery.

Advanced analogs of piperidine and smaller homologues of tropane─3-substituted 6-azabicyclo[3.1.1]heptanes─were synthesized on a large scale using readily available bulk reagents.