The Research Of High Efficient Asymmetric Synthesis Process For (-)- Neoclausenamide

Neoclausenamide is one of the active ingredients obtained from aqueous extract of Ch inese wampee leaf,it belongs to the pyrrolidone compounds. It is the geometric isom ers of amide against the other pyrrolidone components in wampee leaf. The pharmaco logical can only shorten the barbitone effect. In order to study the structure-activity rel ationship of the chiral pyrrolidone compounds, a synthetic route is designed base on t he the domestic and foreign method, and the key intermediates N- methyl- N- benzo yl- alpha, beta epoxy- beta- phenyl acrylic amide synthesis method has been carried for preliminary investigation.Begin with the trans cinnamic aldehyde,through the asymmetric catalytic reaction, ep oxidation reaction and esterification, the key intermediates(2 S, 3 R)- beta phenyl glycidyl methyl oleate is obtained. Choose this intermediate as the raw materials, via condensation, ester amine oxidation of hydroxyl, cyclization, under the condition of al kaline carbonyl reduction, the target product was obtained. The total yield: 20%(cinn amic aldehyde aldehydes) and ee value(98.5%),the target compounds were confirmed by IR, 1 H-NMR, MS.Detailed investigation has been carried on the key intermediate N- methyl- N- benzo yl- alpha, oxidation method of hydroxyl in the synthesis of beta- beta- phenyl epoxy acrylic amic and reduction method for(-)- amide in the C7 stereoselectivity. In the s ynthesis of the key intermediate N- methyl- N- benzoyl- alpha, beta epoxy- beta- p henyl acrylic amide,poor oxidation effect, complex post-processing reaction and serious pollution problems has restricted the industrialization. We have been investigated t he oxidation effect at a variety of oxidant,such as copper sulfate, potassium, active m anganese dioxide, dichromate(PDC), chlorine pyridine chromium acid pyridine salt(PCC), 1, 1-3 acetyl oxygen- 1, 1-2 h- 1, 2- phenyl iodine acyl- 3-(1H)- ketone(D MP)), and the different post-processing methods, the results show that when elected D ess- Martin oxidant to be used for oxidation, the yield can increased from 83.9% to 92%,the reaction is under mild condition, simple post-processing and light pollution, it is the optimal method for oxidation. Literature method has been referenced in the r eduction of stereoseletivity for ketone for(-)-, in the process, Na BH4 and preparation of lithium borohydride, sec-butyl lithium borohydride, zinc borohydride reduction me thod, Corey- Bakshi- Shibata reduction method and Meerwein ponndorf- verley red uction method, BINAL- H reduction method and so many kinds of reducing agent an d the reduction methods for C7 carbonyl reduction have been investigated respectively, it is found that when using(S)- BINAL- H, the single isomers(-)- amide can be ob tained, and when using(S)- CBS reducing agent for reduction, also can obtain a singl e isomers(-) amide, both are in better stereoselectivity and better yield. This article al so preliminary discuss the mechanism of Martin antioxidant oxidation and C7 carbony l stereoselectivity.Since the synthesis route is easy-handling under mild conditions and excellent overall yield and ee value could be obtained, it is proposed that the synthesis route of(-)-Neo clausenamide and(-)-epi-Neoclausenamide is a simple and useful process.