Synthesis Of Optically Active Butyrolactols And Their Applications In The Synthesis Of Alkaloids

Chiron approach is one of the most important way to the synthesis of chiral molecules. Development of multifunctional chiral building blocks or synthons from the chiral pool has been proved to be a powerful strategy for the synthesis of natural products. Alkaloids occur widely in Nature and many of them possess a wide variety of important bioactivities. Therefore, their synthesis have attracted much attention of organic chemists and many synthetic approaches have been developed. The major aim of this thesis is to develop a convenient and practical route for the synthesis of optical active dihydroxy-γ-butyrolactols and use theme as multifunctional building blocks for the the asymmetric synthesis of alkaloids and other biologically active natural products. The main results achieved are listed as follows:1. Concise and practical synthesis of the protected dihydroxy-γ-butyrolactols 14, 29and 30 have been achieved through concise steps and high yields from vitamin C, L- and D-tartaric acid as the cheap starting materials.2. Detailed studies of the Grignard reaction of protected dihydroxy-γ-butyrolactols have revealed that the syn- product is obtained as the major isomer in ratios from 3.6-3.8:1 in high yields, and that the reaction temperature has little effect in stereoselectivity of the reaction.3. Detailed studies of the Grignard reaction of aminoglycoside obtained from dihydroxy-γ-butyrolactols and benzylamine have shown that the syn- product is produced in good yields with excellent diastereoselectivity (syn:anti >95:5), thus providing a new method for the synthesis ofγ-aminoalcohol compounds with high diastereo selectivity. 4. Based on the strategy of the Grignard reaction of dihydroxy-γ-butyrolactols, (+)-Lentignosine was synthesized from 14 and 29 in 6 and 7 steps in 24% and 21% overall yield respectively. This strategy also enabled an efficient synthesis of the key intermediate 291 for DAB 1 from 30 in 3 steps in 14% overall yield.5. Application of the strategy of the Grignard reaction of aminoglycoside, (-)-Deacetylanisomycin was synthesized from 29 in 4 steps in 57% overall yield, and the synthesis of the key intermediate 292 for 2-epi-DAB 1 from 30 in 3 steps in 72% overall yield.