Application of the LADA Strategy for the Synthesis of Unnatural Amino Acids through 1,2-Aryl Migration of Allylic Alcohols.

Unnatural amino acids are versatile building blocks. Herein, we report the application of the LADA strategy for the direct synthesis of unnatural amino acids through 1,2-aryl migration of allylic alcohols. This reaction proceeds under mild conditions, tolerates diverse functionalities, and works smoothly on different thiols.

Decarboxylative oxidation-enabled consecutive C-C bond cleavage.

The selective cleavage of C-C bonds is of fundamental interest because it provides an alternative approach to traditional chemical synthesis, which is focused primarily on building up molecular complexity. However, current C-C cleavage methods provide only limited opportunities. For example, selective C(sp)-C(sp) bond cleavage generally relies on the use of transition-metal to open strained ring systems or iminyl and alkoxy radicals to induce β-fragmentation.

Three-component radical homo Mannich reaction.

Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach.

Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap.

Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group.