Synthesis of the Fused Tetracyclic Thiazinan-4-one Derivatives and Their Anti-tumor Activitiy

Abstract

The benzothiazin-4-one intermediates were prepared by the one-pot three-components condensation from the N-Boc-L-prolinal 1, amino acid ethyl/methyl ester hydrochlorides 2a～2d, and mercaptobenzoic acids 3a～3b. After removal of Boc, the target novel fused tetracyclic thiazinan-4-one derivatives 6～11 were afforded by the intramolecular cyclo-amidation reaction. The absolute configurations of the newly generated chiral carbon (1-C) were determined by the coupling constants of H-1 and H-2 and the X-ray crystallographic structures. The tetracyclic alkaloids were examined for their anti-proliferative activity against Hela and A549 tumor cells. The results showed that some compounds could moderately inhibit the growth of Hela cells, and among them, (13aR,13bR)-1,2,3,13b-tetrahydrobenzo[e]pyrrolo[2',1':3,4]pyrazino[2,1b][1,3]thiazine-5,8(6H,13aH)-dione (6b) was the best one with the IC 50 value of 9.50 μmol/L. However, all the compounds showed no anti-tumor activity against A549.

Insights into Host–Guest Binding in Hydroquinone Clathrates: Single-Crystal X-ray and Neutron Diffraction, and Complementary Computational Studies on the Hydroquinone-CO2 Clathrate

“…42 The table also includes the cocrystal of CO 2 with the explosive CL-20 and, perhaps surprisingly, two cocrystals with bioactive molecules. 43,44 HQ forms three polymorphs under ambient conditions (α-, β-, and γ-forms), and the clathrate-forming β-modification of relevance here exhibits relatively rigid cages with a nearly 5 Å free diameter, depicted in Figure 1. The cavity is formed by six phenyl rings about the sides and two six-membered rings of hydrogen-bonded hydroxyl groups at the top and bottom.…”

“…This rather modest list includes a variety of host–guest systems with host molecules based on cucurbiturils, , paracyclophane, calix[4]­arene, , calix[4]­resorcinarene, , and adamantanetetrabenzoic acid as well as the simpler host molecules hydroquinone ,, and 4-phenoxyphenol . The table also includes the cocrystal of CO 2 with the explosive CL-20 and, perhaps surprisingly, two cocrystals with bioactive molecules. , …”