The scope of intramolecular Diels-Alder and a novel tandem Diels-Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles is disclosed. In the cases examined, the tandem cycloadditions construct three new rings with formation of four new C-C bonds and set all six stereocenters about a central six-membered ring in a single step including three contiguous and four total quaternary centers without a trace of a second diastereomer.

β-Aminoacrylates are reactive intermediates that are useful building blocks in synthesis. General methods for their preparation typically afford α and β disubstitution patterns or β only. Molecules with only α-substituents (β-hydrogen) are much less well-known. A chemoselective reductive tautomerization of α-cyanoacetates, using DIBAL-H, has been developed to access these valuable synthons. α,β-Unsaturated cyanoacetates and α-cyanoketones can, also, be selectively reduced via this methodology. A series of heterocycles were prepared using these β-enamino carbonyl compounds.

The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from d-Garner’s aldehyde and l-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.

A series of substituted dipiperidine compounds have been synthesized and identified as selective CCR2 antagonists. Combining the most favorable substituents led to the discovery of remarkably potent CCR2 antagonists displaying IC50 values in the nanomolar range. Compound 7a had outstanding selectivity over CCR1, CCR3, CCR4, CCR5, CCR6, CCR7, and CCR8 and showed excellent efficacy in adjuvant-induced arthritis model, collagen-induced arthritis model, and allergic asthma model.

Fused pyridine derivativesFused pyridine derivatives R 0450 Intramolecular Diels-Alder and Tandem Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Reactions of 1,3,4-Oxadiazoles. -The title investigation is presented in connection with studies on new synthetic approaches to vinca alkaloids. -(WILKIE, G. D.; ELLIOTT, G. I.; BLAGG, B. S. J.; WOLKENBERG, S. E.; SOENEN, D. R.; MILLER, M. M.; POLLACK, S.; BOGER*, D. L.; J.