A series of adamantoyl L-prolinamides have been synthesized. These compounds have been found to be highly efficient organocatalysts for the Michael addition of aldehydes and ketones to nitroalkenes. Under the optimized reaction conditions, the corresponding Michael adducts were obtained in good yields (up to 95%), excellent enantioselectivities (up to 99% ee) and moderate diastereoselectivities.

Epiandrosterone derivatives-organocatalyzed asymmetric Michael addition of aldehydes to nitroalkenes was investigated. Among the various catalysts, a novel type of epiandrosterone-derived L-prolineamide catalyst was synthesized and exhibited better performance in both catalytic activity and stereoselectivity, providing the products with high yields (up to 98%), excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1 dr), and low catalyst loading (5 mol%).

Two chiral aromatic l-prolinamides were synthesized in high overall yield (95%) from N-Boc-l-proline and served as organocatalysts in asymmetric Michael reactions of aldehydes to nitroalkenes. Under the optimized reaction conditions, (S)-N-tritylpyrrolidine-2-carboxamide 4 was found to be a highly efficient organocatalyst for the Michael addition, and the corresponding Michael adducts were obtained in good yields (up to 94%), with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1 dr).tert-Butyl (S)-2-(benzhydrylcarbamoyl)pyrrolidine-1-carboxylateC24H34N2O4[α]D20 = −78.6 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)(S)-N-Benzhydrylpyrrolidine-2-carboxamideC18H20N2O[α]D20 = −59.1 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)tert-Butyl (S)-2-(tritylcarbamoyl)pyrrolidine-1-carboxylateC29H32N2O3[α]D20 = −38.4 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)(S)-N-Tritylpyrrolidine-2-carboxamideC24H24N2O[α]D20 = −27.0 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)(2R,3S)-2-Methyl-4-nitro-3-phenylbutanalC11H13NO3[α]D20 = +8.3 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Ethyl-4-nitro-3-phenylbutanalC12H15NO3[α]D20 = +8.8 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(R)-2-((S)-2-Nitro-1-phenylethyl)pentanalC13H17NO3[α]D20 = +6.8 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Isopropyl-4-nitro-3-phenylbutanalC13H17NO3[α]D20 = +25.5 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-3-(4-Bromophenyl)-2-ethyl-4-nitrobutanalC12H14BrNO3[α]D20 = +7.6 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-3-(4-Bromophenyl)-2-ethyl-4-nitrobutanalC12H14ClNO3[α]D20 = +9.5 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-3-(2-Chlorophenyl)-2-ethyl-4-nitrobutanalC12H14ClNO3[α]D20 = +11.8 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Ethyl-3-(4-methoxyphenyl)-4-nitrobutanalC13H17NO4[α]D20 = +10.4 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Ethyl-4-nitro-3-(p-tolyl)butanalC13H17NO3[α]D20 = +13.1 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Ethyl-4-nitro-3-(4-(trifluoromethyl)phenyl)butanalC13H14F3NO3[α]D20 = +9.8 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3R)-2-Ethyl-3-(furan-2-yl)-4-nitrobutanalC10H13NO4[α]D20 = +17.2 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Isopropyl-4-nitro-3-(p-tolyl)butanalC14H19NO3[α]D20 = +66.1 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-3-(4-Bromophenyl)-2-isopropyl-4-nitrobutanalC13H16BrNO3[α]D20 = +92.5 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-2-Isopropyl-4-nitro-3-(p-tolyl)butanalC14H19NO3[α]D20 = +78.3 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)(2R,3S)-3-(2-Chlorophenyl)-2-isopropyl-4-nitrobutanalC13H16ClNO3[α]D20 = +107.1 (c 1.0, CHCl3)Source of chirality: newAbsolute configuration: (2R,3S)(2R,3R)-2-Isopropyl-4-nitro-3-(thiophen-2-yl)butanalC11H15NO3S[α]D20 = +29.3 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2R,3S)

A solvent-free intermolecular Diels–Alder cycloaddition of piperine on silica gel is described. The dimerization of piperine in the presence of silica gel gives better yields than that under the condition of only heating. The new procedure is simple, clean, and easy to operate. It has higher yields and can be completed in short time.

A series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, have been designed and synthesized in nine steps starting from ursodeoxycholic acid. The in vitro antitumor activity of the target compounds has been evaluated against HCT-116, MCF-7, K562, and SGC-7901 cell lines. The pharmacological results showed that most of the prepared compounds display excellent selective cytotoxicity toward HCT-116, MCF-7, and K562 cell lines. Particularly, compounds 10c, 10f and 10g show high inhibitory activity on these human cancer cell lines (IC50: 2.39–9.34 μM). Conversely, all compounds are generally inactive against SGC-7901, with only 10b having IC50 below 50 μM.Graphical abstractA series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, were synthesized and evaluated in vitro antitumor activity against HCT-116, MCF-7, K562, and SGC-7901 cell lines.Download full-size imageHighlights► Ursodeoxycholic acid derivatives, N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, were designed and synthesized. ► The in vitro antitumor activity was evaluated against four cancer cell lines. ► Three active compounds show high inhibitory activity on three human cancer cell lines.