ABSTRACT
A chiral amino alcohol based ligand was found to promote the highly enantioselective addition of terminal conjugated diynes to aromatic and aliphatic aldehydes. The combination of easily available C2 -symmetric (R)- and (S)-BINOL with Ti(OiPr)4 , Zn powder, and EtI was also found to catalyze the asymmetric addition of 1,3-diynes to aldehydes under mild reaction conditions, and thus, both enantiomers of the chiral conjugated diynols could be prepared with high enantioselectivities. The resulting optically active conjugated diynols were found to have potential anticancer activities with significant differences against HepG2 and HeLa cancer cells, and remarkable enantioselective cytotoxicity was observed for the first time.
Subject(s)
Aldehydes/chemistry , Amino Alcohols/chemistry , Antineoplastic Agents/chemistry , Diynes/chemistry , Aldehydes/chemical synthesis , Aldehydes/pharmacology , Amino Alcohols/chemical synthesis , Amino Alcohols/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Catalysis , Diynes/chemical synthesis , Diynes/pharmacology , HeLa Cells , Hep G2 Cells , Humans , Ligands , Naphthols/chemical synthesis , Naphthols/chemistry , Naphthols/pharmacology , Neoplasms/drug therapy , Stereoisomerism , Titanium/chemistry , Zinc/chemistryABSTRACT
P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-ß-methylstyrenes, with up to 91 % ee. Molecular modeling studies provide insights into the different catalytic activity of the T213M mutant and the T213Y mutant in the epoxidation of cis-ß-methylstyrene. The results of the calculations also contribute to a better understanding of the substrate specificity and configuration control for the regio- and stereoselective peroxygenation catalyzed by the T213M mutant.
Subject(s)
Epoxy Compounds/chemistry , Mixed Function Oxygenases/chemistry , Protein Engineering/methods , Styrene/chemistry , Catalysis , Models, Molecular , StereoisomerismABSTRACT
An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.