No abstract

Since its discovery in the late 1960s, the Morita–Baylis–Hillman (MBH) reaction has remained a powerful carbon–carbon σ-bond-forming transformation, producing small polyfunctionalized molecules. While commonly catalyzed by Lewis basic organic molecules such as tertiary amines and phosphines, several advances in functional catalysts and reaction conditions have been made in order to improve the reaction rate, substrate scope, and enantioselectivity. The goal of this Review is to give an updated summary of the main improvements made in catalytic systems for the MBH reaction over the past decade until nowadays. We hope this account will instigate further investigations in order to circumvent the remaining challenges of this fascinating transformation.

We describe that vinyl-oxadiazoles function as a new and efficient nucleophilic partner for the Morita−Baylis− Hillman (MBH) reaction. The reaction between 5-vinyl-3-aryl-1,2,4-oxadiazoles and aromatic and aliphatic aldehydes, catalyzed by DABCO in the absence of solvent, showed high efficiency to afford a new class of heterocyclic MBH adducts with potential biological activity on yields up to 99% and short reaction times. These synthetically attractive adducts bear a heterocyclic scaffold of large pharmaceutical and commercial interest associated with a plethora of biological effects and technological applications. We also demonstrate their synthetic usefulness by a photoinduced addition reaction to a polyfunctionalized amino alcohol.

Fifty-one new synthetic compounds belonging to four different series, namely (1a) substituted aryl-4-(substituted phenyl) succinimide; (1b) N-(substituted methyl)-4-(heterocyclic) succinimide; (2) heterocyclic 4-(5′-nitro-2-furyl) thiazoles; (3) substituted aryl-4-(3′, 4′-dihydroxy phenyl) thiazoles, and (4) phenyl-N, N-1,2,3-bis-methoxy carbonyl guanidines were screened for antituberculous activity using a conventional broth dilution test (BDT) and a liquid scintillation radiometric method (LSRM). Eight compounds showed in vitro activity. LSRM showed 100% agreement with BDT. LSRM is completed within 60 h, while BDT requires 8–9 days. Unlike BDT, LSRM allowed one to measure the graded changes in the metabolism and the growth rate of Mycobacterium tuberculosis in response to various concentrations of the drug. It permits the measurement of the relative prolongation of the replication time by the drug or the test compound. With LSRM it was possible to detect the phase of growth during which the test compound shows or begins its antituberculous activity. It improves our understanding of the antituberculous activity of the test compound and hence is more advantageous. It is rapid, reliable, quantitative and more sensitive than BDT. LSRM is thus suitable for the evaluation of new drugs.