摘要
从手性氨基酸L-苏氨酸开始合成的小生物分子模拟物化合物B4-苯基-2-甲基-5-氧-吗啉-3-羧酸是重要的模拟天然药物分子中间体。[1]根据改良的实验操作,按图1可以合成化合物B:从溶于等当量1M氢氧化钠的L-苏氨酸开始,在低温下,加入苯甲醛和硼氢化钠,反应完毕后,用浓盐酸调pH至7,可以得到苄基取代的L-苏氨酸A[2];将A分批加入到氯乙酰氯中搅拌数分钟,然后用7.5M氢氧化钠调pH至5-6,得到B.化合物B可以在四氢呋喃中用硼氢化钠逐级还原,经中间体D1和D2得到化合物D.[1]
The small molecular natural analog 4-Benzyl-2-methyl-5-oxo-morpholine-3-carboxylic acid starting from the chiral amino acid L-Threonine is the important natural drug molecular intermediate.[1]According the improvements of the experimental processes in Figure 1,compound B can be synthesized:starting from L-Threonine dissolved in the equal amount of 1M NaOH,under low temperature,PhCHO and NaBH_4 can be added,when finished,concentrated HCI is used to adjust pH to 7[2],compound A can be obtained;A directly is added to CICH_2COCI to stirring for several minutes and then 7.5M NaOH adjust pH to 5-6,compound B can be obtained.
引文
[1]Alexanda Meinzer ect.Properties and Reactions of Substituted 1,2-Thiazetidine 1,1-dioxides:Chiral Mono-and Bicyclic 1,2-Thiazetidine 1,1-dioxides fromα-Amino acids Helvetica Chimica Acta 2004 87 90105;
[2]G.R.Browm ect.Chinal Synthesis of 3-substituted morpholines via serine enantiomers and reductions of 5-oxomorpholine-3-carboxylates J.Chem.Soc.Perkin Trans 1985 112 25772580
