A facile, single pot diastereoselective access to seven and eight-membered aza-heterocycles.

What is it about?

A facile, single pot diastereoselective access to seven and eight-membered aza-heterocycles was developed by using b-lactam-synthon approach. The developed protocol does not involve the typical intricacies viz.the use of expensive transition metal catalysts and high boiling solvents, associated with the convenient protocols

Featured Image

Why is it important?

Medium sized ring lactones are considered as the crucial structural motifs in naturally occurring bioactive molecules.1,2Theyhave received special attention because of their numerous applications such as drug candidates,3catalysts4and materials.5Amongthe various activities exhibited by these compounds, their potential as non-nucleoside HIV-1 reverse transcriptase inhibitor,6histaminereceptor agonist,7calcium antagonists,8antidepressants,9analgesics,10anxiolytic,11antiserotoninergic and anticancer activity against breast cancer cells is well established.12Past few years have witnessed the development of a number of synthetic protocols for macro-lactonization viz. Corey–NicolaouS-pyridylesterlactonization,13Mukaiyamaoniumsalt,14Masamunethiol ester activation,15Mitsunobu alcohol activation,16Shiina ben-zoic anhydride,17Yamaguchi mixed anhydride18and Keck–SteglichDCC/DMAPHCl activation19methods. However, these methods are invariably associated with a number of drawbacks including long reaction time, low to average yields, use of expensive transition metal catalysts and high boiling solvents. Moreover, the synthesis of medium-sized ring lactones is considered arduous because of the unfavorable enthalpy and entropy considerations.20Thus the development of facile and efficient methodologies to macrolactonization with readily available starting materials and reagents remains a challenging task.b-Lactams are evergreen bioactive molecules exhibiting broad medicinal and pharmacological profiles,21and as the key intermediates in the organic synthesis.22b-Lactamsynthonmethodologyisconsideredasapowerfularmamen-tarium available with the synthetic chemists as its applications the field of synthesis and drug discovery is phenomenal. The approaches have been extensively used for the synthesis of oligopeptides, enantiopure succinimides, 1,4-diazepines, piperazines, nonprotein amino acids, peptidomimetics along with differently sized heterocycles of medicinal interest, that is, indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cryptophycins, lankacidins, etc

Perspectives