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A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure−activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(α-naphthyl)methanol [(α-Np)2CHOH] as an achiral alcohol, and (+)-benzotetramisole (BTM) as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral α-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure.

A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl4, the desired one-pot coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole proceeded to afford the corresponding 3,4,4-triaryl-1-butene 7 in high yield. The iodocarbocyclization of the coupling product and the successive elimination of hydrogen iodide forming the olefin part, followed by the migration of the double-bond afforded the common synthetic intermediate of lasofoxifene (1) and nafoxidine (2) via a very concise procedure. Additionally, the syntheses of their positional isomers inv-lasofoxifene (3) and inv-nafoxidine (4) were also achieved through very convenient protocols.

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.

We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(α-naphthyl)methanol [(α-Np)2CHOH] as an achiral alcohol, and (+)-benzotetramisole (BTM) as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral α-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure. [ABSTRACT FROM AUTHOR]

A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl4, the desired one-pot coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole proceeded to afford the corresponding 3,4,4-triaryl-1-butene 7 in high yield. The iodocarbocyclization of the coupling product and the successive elimination of hydrogen iodide forming the olefin part, followed by the migration of the double-bond afforded the common synthetic intermediate of lasofoxifene (1) and nafoxidine (2) via a very concise procedure. Additionally, the syntheses of their positional isomers inv-lasofoxifene (3) and inv-nafoxidine (4) were also achieved through very convenient protocols. [ABSTRACT FROM AUTHOR]

A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure–activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). [ABSTRACT FROM AUTHOR]

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality. [ABSTRACT FROM AUTHOR]