Enzyme-assisted kinetic resolution of novel 2-naphthol mannich bases
LE3 .A278 2007
Bachelor of Science
Estradiol (the most active estrogen) is a steroid hormone found in the body. It plays a role in bone maturation, the regulation of the lipid profile in blood, the development of sexual characteristics, and the growth of breast cancer cells. Selective estrogen receptor modulators (SERMs) are synthetic molecules designed to stimulate or inhibit the effects of estrogen. Tamoxifen and raloxifene are currently available SERMs used for the treatment of breast cancer and osteoporosis respectively. The structure of potential designed SERMs mimics the estrogen backbone and placement of hydroxyl groups. Induction of a chiral center serves to increase the specificity of the molecule, and the addition of an amino side-chain effectively emulates the structure of clinically used SERMs. The purpose of this research is to design a method for the synthesis of novel potential SERMs. To achieve this, enantioselective synthesis of structurally simpler analogs of designed potential SERMs was investigated. The Mannich reaction was used to synthesize 2-naphthol Mannich bases using 2-naphthol, 4-piperidinol, and 10 different aromatic aldehydes. These 10 chiral Mannich bases were then resolved using an enzyme-assisted chemo, regio, and enantioselective acetylation process in an organic solvent. The optical enrichment was achieved as evidenced by measurement of the optical rotation of the mono-acetylated product and unreacted dihydroxy compound.
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