Malie acid-A Versatile Chiral Building Block in the Enantioselective Total Synthesis of Natural Products and in Synthetic Methodologies

Building block-approach is one of the basic strategies used by nature in biogenetic synthesis. Naturally occurring L-alpha-amino acids , L-alpha-hydroxy acids , D-mono-sugars , and terpenes , being cheap and easily available in enantiopure forms , have found widespread applications enantioselective synthesis as chiral building blocks. L-Malic acid, an L-alpha-hydroxy diacid, is a readily available and cheap natural chiron, D-malic acid is also commercially available although it is more expensive. With all of the four carbon atoms transformable or functionalizable , malic acid serves as a versatile C-4 building block in organic synthesis for enantioselective synthesis. In this review , the progress in the applications of malic acid in organic synthesis is summarized. Firstly, the transformations of malic acid into a variety of advanced chiral C-4 building blocks are compiled. Secondly , selected examples on the applications of these versatile intermediates in the total synthesis of complex natural products in recent years are presented. Besides , the developments of malic acid-based new synthetic methodologies including the contribution from one of the authors' laboratory are highlighted. An outlook for future development of malic acid-based synthetic strategy is provided.