| Most polyketide natural products are chiral and exist in enantiomerically pure form, often containing more than one stereogenic centers. During synthesis of the polyketide natural products, these centers can be either derived from nature's chiral pools or from resolution of racemic mixtures. Alternatively, the chiral center can be installed using asymmetric catalysis. The asymmetric catalysis approach has the potential to be the most efficient strategy for the construction of libraries of stereochemical polyketide natural products by the installation stereochemistry into the achiral starting materials.;Asymmetric catalysis was used to synthesize two categories of polyketide natural products, cryptocaryols and tetrahydrolipstatin, in 25 and 10 longest linear steps, respectively. In addition, five cryptocaryol and eight tetrahydrolipstatin stereochemical analogues were also accessed, which demonstrated the versatility of the catalytic asymmetric approach. The asymmetric catalysis strategy is also applied to an ongoing project the total synthesis of EBC-23.;These stereochemical analogues were used to develop structure activity relationship profiles for cryptocaryols and tetrahydrolipstatin cytotoxicity against cancer cell lines (e.g. MCF-7 and H460). |
