Studies On The Stereoselective Synthesis Using 5-Substitute-2(5H)-furanone As Chiral Synthon

Stereoelective synthesis of optically pure chiral compounds with multiple functional groups and chiral centers is an attractive field in organic synthesis and drug preparation. One of the important routes to obtain chiral compounds is using chiral substrates or chiral auxiliaries induced asymmetric synthesis. In this thesis, we stereoselectively synthesized a sereies of novelβ-substituted butyrolactone detrivatives and spiro-cyclopropane-butyrolactone compounds baring amino acid or carbohydrate building block by using 5-substituted-2(5H)-furanone as starting material. Additionally, we synthesized novel chiron 5-(N-Ts-L-prolinoxyl)-2(5H)-furanone.Ⅰ.5 Chiralβ-substituted butyrolactones were synthesized through the Michael addition of amino acids or carbohydrates to 5(R)-(l-menthyloxy)-2(5H)-furanone. When D-glucose was used as nucleophile, the Michael adduct was not produced, but a novel compound 8, the self-addition of 5(R)-(l-menthyloxy)-2(5H)-furanone, was generated accidentally. All the synthesized compounds were characterized through IR, 1H NMR,13C NMR and HRMS, and the absolute configuration of compound 8 was determined by single crystal X-ray diffraction analysis. Ⅱ.7 Novel spiro-cycliopropane-butyrolactones with 4 sterogenic centers 12a-12g were synthesized through the tandem double Michael addition/intermolecular nucleophilic substitution of amino acids or carbohydrates to 5(R)-(l-menthyloxy)-3-Br-2(5H)-furanone 9. At the same time, a mono Michael addition/intermolecular elimination product 14, aβ-substituted butenolide derivative, was obtained also. All the synthesized compounds were characterized through IR, 1H NMR,13C NMR and HRMS, and their absolute configurations were determined by single crystal X-ray diffraction analysis. This results provide new synthetic route for the complex compounds with multi-functional groups and chiral centers, which may display biologically activity. We also found that the reactant concentration can affect the products. Lower concentration is mainly suitable for generating spiro-cyclopropane compounds, while higher concentration benefits forβ-substituted butenolide derivative. The study on the mechanism is under progress now.Ⅲ. The isomers 5-(N-Ts-L-prolinoxyl)-2(5H)-furanone (16a+16b) were synthesized through the condensation reaction of N-Ts-L-proline with 5-hydroxyl-2(5H)-furanone. Pure isomer 16a was obtained in 15% yield by recrystalization. The chemical structure of 16a was characterized through IR,1HNMR, 13CNMR and HRMS, and the absolute configuration was determined by X-ray single crystal diffraction analysis. This compound can be used as novel chiral synthon to synthesize more chiral compounds.