Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration-oxidation of dienes followed by Buchwald-Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g. 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicit

Synthesis of novel crown ether-squaramides and their application as phase-transfer catalysts

t: This work presents the synthesis of six new phase-transfer organocatalysts where the 15 squaramide unit is directly linked to the nitrogen atom of an aza-crown ether. Four chiral skeletons, 16 namely hydroquinine, quinine, cinchonine (cinchonas), and α-D-glucopyranoside were responsible 17 for the asymmetric construction of an all-carbon quaternary stereogenic center in α-alkylation and 18 Michael addition reactions of malonic esters. We intended to investigate the effects of different chi- 19 ral units and that of crown ethers with different sizes on catalytic activity and enantioselectivity. 20 During extensive parameter investigations, both conventional and emerging green solvents were 21 screened, providing valuable α,α-disubstituted malonic ester derivatives with excellent yields (up 22 to 98%). Furthermore, the products are amenable to chemoselective transformation and could be 23 successfully converted to the corresponding α,α-disubstituted amino acid derivatives through Cur- 24 tius rearrangement