Three Cephalotaxus Ester Alkali Derivatives

The total synthesis of racemic 15,16-dimethylene dioxy-16-methoxyl-cephalotaxine (3) and the preliminary resolution of its racemic precursor,15,16-demethylene dioxy-16-methoxyl cephalotaxine(2),have been reported in previous master's thesis.In this thesis,the above work is continued, the racemic 2(±) was resolved into a pair of enantiomer.Reduction of 2(-) with sodium boron hydride, the target compound, 15.16-demethylene dioxy-16-methoxyl cephalotaxine 3(-) (3S,4S,5R) with the same configuration as natural cephalotaxine was obtained. Similarly, its enantiomer 3 (+) (3R, 4R,5S) was obtained from 2(+).The reported asymmetric semi-synthetic method was utilized for preparing the 15,16-demethylene dioxy-16-methoxyl deoxyharringtonine 1(-) and its enantiomer 1(+). The key step in this route-asymmetric condensation of cepahlotaxine-α-ketone (4) with chiral sulphur reagent 25(+), was studiedin detail. In the previous report the ratio of C₂'R:C₂'S is 3:1. In our experiment, a modified way of addition aproc (?)dure of the chiral reagent was tried. As a result, the ratio of C₂'R:C₂'S of products was raised to 9.4:1(d.e.30.8%). The modified operation significantly increased the stereoselec-tivity of this reaction.The 15,16-demethylene dioxy-16-methoxyl deoxyha-rringtonine 1(-) (3S,4S,5R,2'R) with the configuration of all chiral centers possibly same as natural deoxyharringtonine (8), and its enantiomer 1(+) were synthesized respectively from 15,16-demethylene dioxy-16-methoxyl cephalotaxines 3(-) and 3(+) according to the...