Evaluation and molecular modelling of bis-Schiff base derivatives as potential leads for management of diabetes mellitus.

Developing a medication to cure and manage diabetes mellitus complications is of interest in medicinal chemistry. Toward this end, six bis-biphenyl-salicylaldehyde Schiff base derivatives have been evaluated for their α-glucosidase inhibition, antiglycation and anti-inflammation potentials. Four compounds (compounds 2-5) showed an excellent α-glucosidase inhibitory effect superior to that produced by acarbose. Additionally, the docking study revealed that these compounds are anchored within the binding pocket of α-glucosidase via hydrogen bonding, π-stacking and hydrophobic interactions, comparable to a high number of hydrogen bonding involved in anchoring acarbose. Interestingly, all tested compounds showed varying degrees of antiglycation activity with superior activity for two of them (compound 1 and compound 6) compared to the standard rutin. Moreover, the results indicated an outstanding anti-inflammatory activity for two compounds (compounds 1 and 6) compared to ibuprofen.

Calcium-Mediated Catalytic Synthesis of 1-(Diorganylamino)-1,4-diphenyl-4-(diphenylphosphanyl)buta-1,3-dienes.

The hydroamination of diphenylbutadiyne with 1 equiv of the secondary amines HNRR' (R/R' = Ph/Ph, Ph/Me, and pTol/Me) in the presence of catalytic amounts of the tetrakis(amino)calciate K2[Ca{N(H)Dipp}4] (Dipp = 2,6-diisopropylphenyl) yields the corresponding 1-(diorganylamino)-1,4-diphenylbut-1-ene-3-ynes as a mixture of E/Z isomers. These tertiary alkenylamines react with diphenylphosphane to form RR'N-C(Ph)═CH-CH═C(Ph)-PPh2 [R/R' = Ph/Ph (1), Ph/Me (2), and pTol/Me (3)] in the presence of catalytic amounts of [(THF)4Ca(PPh2)2] or of the same calciate K2[Ca{N(H)Dipp}4]. Whereas the hydroamination is regio- (amino group in 1-position) but not stereoselective (formation of E and Z isomers), this second hydrofunctionalization step is regio- (phosphanyl group in 4-position) and stereoselective (only E isomers are formed), finally leading to mixtures of (E,E)- and (Z,E)-1-(diorganylamino)-1,4-diphenyl-4-(diphenylphosphanyl)buta-1,3-dienes.

Oxidation products of calcium and strontium bis(diphenylphosphanide).

The tetrahydrofuran adducts [(thf)(4)M(PPh(2))(2)] (M = Ca, Sr) are air sensitive and can easily be oxidized by chalcogens. Metalation of diphenylphosphane oxide, diphenylphosphinic acid, and diphenyldithiophosphinic acid as well as salt metathetical approaches of the potassium salts with MI(2) allow the synthesis of [(thf)(4)Ca(OPPh(2))(2)] (1), [(dmso)(2)Ca(O(2)PPh(2))(2)] (2), [(thf)(3)Ca(O(2)PPh(2))I](2) (3), [(thf)(3)Ca(S(2)PPh(2))(2)] (4), [(thf)(2)Ca(Se(2)PPh(2))(2)] (5), [(thf)(3)Sr(S(2)PPh(2))(2)] (6), [(thf)(3)Sr(Se(2)PPh(2))(2)] (7), and [(thf)(2)Ca(O(2)PPh(2))(S(2)PPh(2))](2) (8), respectively. The diphenylphosphinite anion in 1 contains a phosphorus atom in a trigonal pyramidal environment and binds terminally via the oxygen atom to calcium. The diphenylphosphinate anions act as bridging ligands leading to polymeric structures of calcium bis(diphenylphosphinates). Therefore strong Lewis bases such as dimethylsulfoxide (dmso) are required to recrystallize this complex yielding chain-like 2. The chain structure can also be cut into smaller units by ligands which avoid bridging positions such as iodide and diphenyldithiophosphinate (3 and 8, respectively). In general, diphenyldithio- and -diselenophosphinate anions act as terminal ligands and allow the isolation of mononuclear complexes 4 to 7. In these molecules the alkaline earth metals show coordination numbers of six (5) and seven (4, 6, and 7).