Synthesis and in Vitro Cytotoxicity Evaluation of Jadomycins.

Jadomycins, which are benzo[b]phenanthridine-type alkaloids isolated from Streptomyces venezuelae ISP5230, exhibit cytotoxic activity against multidrug-resistant breast cancer cells. We have previously achieved the total synthesis of jadomycins using the direct arylation of juglone as a key step. In this study, we achieved the total synthesis of jadomycin T and jadomycin aglycons using L-threonine and 1-amino-2-propanol as nitrogen sources. Additionally, we evaluated the cytotoxic activity of eight compounds, including glycosides, jadomycin T, and their corresponding aglycons, in eight types of tumor cells. The evaluated jadomycins tended to exhibit stronger cytotoxic activity as aglycons than as glycosides. Although the presence of a 1,3-oxazolidine ring derived from an amino acid was not essential, the presence of the 1,3-oxazolidine ring showed strong activity when the ring had a carboxyl group. Furthermore, compared to the non-natural isomer at a different position on the phenolic hydroxyl group, the naturally occurring phenanthroviridin aglycon exhibited stronger cytotoxic activity. In addition, this study suggests that jadomycins may become lead compounds for the treatment of brain tumors; however, further studies on their ability to penetrate the blood-brain barrier are required.

Pulsed laser photolysis vacuum UV laser-induced fluorescence kinetic study of the gas-phase reactions of Cl(2P3/2) atoms with C3-C6 ketones.

The gas-phase reactions of Cl atoms with acetone, butanone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, and cyclopentanone at 295 +/- 2 K were studied using pulsed laser photolysis vacuum UV laser-induced fluorescence (PLP-LIF) techniques. Cl(2P(3/2)) atoms were produced by photolysis of Cl2 at 351 nm and monitored by LIF spectroscopy at 134.72 nm (3p(5) 2P(3/2)-3p(4)4s 2P(3/2) transition). Rate coefficients for reactions of Cl atoms with acetone, butanone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, and cyclopentanone are (2.30 +/- 0.12) x 10(-12), (4.08 +/- 0.21) x 10(-11), (1.23 +/- 0.13) x 10(-10), (8.87 +/- 0.92) x 10(-11), (2.08 +/- 0.32) x 10(-10), (1.43 +/- 0.19) x 10(-10) and (1.16 +/- 0.12) x 10(-10) cm3 molecule(-1) s(-1), respectively. The results for acetone and butanone are consistent with previous studies. The results for 2-pentanone, 3-pentanone, 2-hexanone, and 3-hexanone are approximately a factor of 2-3 higher than those from previous absolute rate studies. Likely explanations for these discrepancies are discussed. Tropospheric lifetimes of ketones with respect to reaction with Cl atoms are estimated and discussed.