Containing ¦Ã-lactone Skeleton Of The Asymmetric Synthesis Of Natural Products

Substituted y-lac tone is a key structural feature found in a number of natural and/or bioactive compounds. The interesting bioactivities demonstrated by these compounds combined with their unique structural feature make this class of compounds attractive synthetic targets.The aim of present thesis is to develop a flexible asymmetric approach to various substituted y-lactones. Beside, the origins of the high regioselectivity observed during the Grignard addition to (5)-malimide I will subjected to preliminary study.The main results and conclusions obtained in this thesis are summaried as follows:First, the tandem ring-opening/reduction reaction for the conversion of y-lactam II to y-hydroxylamide III was studied. It was showed that only NaBH4 in MeOH or EtOH was capable to achieve the desired transformation. However, although the chemical yields are good (80-85%), the stereoselectivities were mediocre (the molar ratio between ami and syn is in the range of 50:50-41:59) and the diastereomers were inseparable by column chromatography at this stage.Second, conditions were defined (HC1, in dioxane. heating) for the transformation of in to IV and V, and the diastereomers obtained were separable at this stage. Lactones IV and V were converted respectively to VI and VD. Four pairs of diastereomers VI/VB (R=Me, Et, n-Eu. n-C7H15) were prepared by this procedure.Third, the further elaboration of VI (R=n-Bu) lead to VI, which constituted a formal asymmetric synthesis of trans-whisky lactone IX. The elaboration of VI (R=Me) lead to the asymmetric synthesis of naturally occurring lactones (+)-blastmycinolactol X and (-)-blastmycinone XI. The asymmetric synthetic of(+)-NFX-2 XI was also attempted with paritial success.Finally, based on PM3 calculations, a working model to account for the high regioselectivity observed during the Grignard reagents addition to (S)-malimide I was proposed.