5055-10-7

Synthesis of (S)-2-methyl-3-fluorophenyl cyclopentanone methyl ester (1S)-1 has been achieved by both inter-and intramolecular alkylation reactions on multigram scale, using chiral pool reagents. The intramolecular variant is a novel example of a chiral bis-electrophile reacting with a carbon nucleophile to form an enantiomerically pure all-carbon quaternary center.

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, or pharmaceutically acceptable salts thereof, compositions thereof, and methods of their use. The condition or disorder mediated by HDAC comprises a neurodegenerative pathology. Accordingly, also provided is a method of treating a neurodegenerative pathology mediated by HDAC in a subject in need of such a treatment, comprising administering to the subject a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt thereof, described herein.

Provided are certain histone deacetylase (HDAC) inhibitors of Formula (I), compositions thereof, and methods of their use.

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

The syntheses of four new, differently O-substituted 3-hydroxypyrroline N-oxides and the first 3-amino analogue have been performed by the use of a strategy involving double nucleophilic displacement of the corresponding dimesylates by hydroxylamine and oxidation of the resulting 1-hydroxypyrrolidines. The regioselectivity data of the oxidation reactions nicely confirm the mechanistic hypothesis, which explains the dependence on the electronic nature of the substituent. The trend of the regioselectivity ratio has useful predictive value. Practical complete regioselection has been obtained by substitution with a benzoyloxy functionality. The O-allyl-substituted nitrone is not stable in the reaction conditions, undergoing immediately an intramolecular cycloaddition reaction with complete stereocontrol and inversion of regio- and stereoselectivity with respect to the intermolecular case.

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