Isolation, Identification, and Biological Activities of a New Chlorin e6 Derivative.

Chlorin e6 is a well-known photosensitizer used in photodynamic diagnosis and therapy. A method for identifying and purifying a novel process-related impurity during the synthesis of chlorin e6 has been developed. Its structure was elucidated using NMR and HRMS. This new impurity is formed from chlorophyll b rather than chlorophyll a, which is the source of chlorin e6. The intermediates formed during chlorin e6 synthesis were monitored using HPLC-mass spectrometry. This new impurity was identified as rhodin g7 71-ethyl ester, the structure of which remains unknown to date. The cytotoxic effects of this novel compound in both dark and light conditions were studied against five cancer cell lines (HT29, MIA-PaCa-2, PANC-1, AsPC-1, and B16F10) and a normal cell line (RAW264.7) and compared to those of chlorin e6. Upon irradiation using a laser at 0.5 J/cm2, rhodin g7 71-ethyl ester demonstrated higher cytotoxicity (2-fold) compared to chlorin e6 in the majority of the cancer cell lines. Furthermore, this new compound exhibited higher dark cytotoxicity compared to chlorin e6. Studies on singlet oxygen generation, the accumulation in highly vascular liver tissue, and the production of reactive oxygen species in MIA-PaCa-2 cancer cells via rhodin g7 71-ethyl ester correspond to its higher cytotoxicity as a newly developed photosensitizer. Therefore, rhodin g7 71-ethyl ester could be employed as an alternative or complementary agent to chlorin e6 in the photodynamic therapy for treating cancer cells.

Enantioselective Cyclopropanation/[1,5]-Hydrogen Shift to Access Rauhut-Currier Product.

A Michael addition initiated cyclopropanation/[1,5]-hydrogen shift has been developed for the enantioselective synthesis of Rauhut-Currier products. The reaction of α-alkyl diazoesters and in situ generated o-quinone methides proceeds in the presence of chiral oxazaborolidinium ion, providing Z-stereocontrolled Rauhut-Currier products in high yields (up to 96%) with excellent Z/E selectivities (>20:1) and enantioselectivities (up to >99% ee). The synthetic utility was illustrated by conversion of the product to 3,4-dihydrocoumarins with two adjacent chiral stereocenters.

Asymmetric Synthesis of Enantioenriched 2-Aryl-2,3-Dihydrobenzofurans by a Lewis Acid Catalyzed Cyclopropanation/Intramolecular Rearrangement Sequence.

A cyclopropanation/intramolecular rearrangement initiated by the Michael addition of in situ generated ortho-quinone methides (o-QMs) has been developed for the enantioselective synthesis of 2-aryl-2,3-dihydrobenzofurans containing two consecutive stereogenic centers, including a quaternary carbon atom. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in excellent yields (up to 95 %) with excellent stereoselectivity (up to >99 ee, up to >20:1 d.r.).

Iodine-mediated construction of polyfunctionalized arylazopyrazoles from ß-ketoesters or 2-arylpyrazol-3-ones and arylhydrazines.

This paper describes step-economic iodine-mediated construction of functionalized arylazopyrazoles in the presence of catalytic AgNO3 starting from simple ß-ketoesters and two equivalents of arylhydrazines. This cascade reaction includes in situα-iodination of ß-ketoesters, pyrazol-3-one formation, substitution with a nitrogen nucleophile, and oxidation/aromatization.

Novel one-pot synthesis of diverse γ,δ-unsaturated ß-ketoesters by thermal cascade reactions of diazodicarbonyl compounds and enol ethers: transformation into substituted 3,5-diketoesters.

Sequential Wolff rearrangement of α-diazo-ß-ketoesters followed by trapping of the ketene intermediates with enol ethers generated a variety of γ,δ-unsaturated ß-ketoesters. This method involves a novel thermal cascade reaction and allows the synthesis of γ,δ-unsaturated ß-ketoesters with trans-stereochemistry under catalyst-free conditions. The synthesized compounds were further transformed into novel 3,5-diketoesters, which were used for the synthesis of naturally occurring 2-pyrone and 1-naphthoic acid ester.

Efficient one-pot synthesis of novel and diverse tetrahydroquinolines bearing pyranopyrazoles using organocatalyzed domino Knoevenagel/hetero Diels-Alder reactions.

A new synthetic route to biologically interesting diverse tetrahydroquinolines bearing pyranopyrazoles was developed by reacting pyrazolones and N, N-dialkylated aminobenzaldehydes in the presence of EDDA. The key strategy underlying the methodology used was the domino Knoevenagel/hetero Diels-Alder reaction. This synthetic method provides a variety of novel tetrahydroquinolines in good yields.