| This thesis contains two chapters:(1)Asymmetric synthesis of chiral intermediate of(-)-Cephalotaxine;(2)Synthetic studies toward(-)-Cephalotaxine.Chapter I:Key chiral intermediate 2-5 was critical for the synthesis of(-)-Cephalotaxine whose optical purity was effected by the chirality of 2-5.The purpose of this chapter was mainly concentrated on the asymmetric synthesis of key intermediate 2-5.Stevens rearrangement reaction was applied to obtain 2-5.The effect of product chirality was mainly explored by altering different reaction conditions and substrate structures.Finally,the best reaction condition was confirmed to be Potassium tert-butoxide was used as base in THF and at 0 ? so that ee could reach to 73%.At the same time,the structures of the ester groups had little effect on the chirality of products.Chapter II:Cephalotaxus alkaloids are a class of cytotoxic natural products.Cephalotaxine has received extensive attention due to its special pentacyclic structure and the antitumor activity of harringtonine and homoharringtonine.In this chapter,multiple schemes were designed and conducted leading to synthesis of(-)-Cephalotaxine.In the first scheme,3,4-dihydroxybenzaldehyde was used as starting material to gain compound 3-6 and 3-7,which were coupled with L-Proline methyl ester to give compounds 3-15 and 3-16.Scheme 2 started from L-Proline methyl ester hydrochloride to obtain compound 3-14,which was then coupled with compound 3-6 and 3-7.After that,they went through reduction to give compound 3-19 and 3-20.In scheme 3,L-Proline was selected as starting material to obtain optically pure compound 2-5 over 4 steps,which could approach key intermediate 3-23 via a few steps.Optical pure compound 2-5 was obtained through above two chapters in 57%yield,which greatly improved the optical purity of(-)-Cephalotaxine intermediates;key intermediate 3-23 was synthesized over a series of reactions,which was then coupled with compound 3-6 and 3-7,and post-exploration work was still in progress. |
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