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本文报道以L-缬氨酸为手征性助剂,DL-丙氨酸为原料,(3S,6SR)-2,5-二甲氧基-3-异丙基-6-甲基-3,6-二氢吡嗪(1)为杂环中间体,(2R,3SB)-O-甲基-a-甲基丝氨酸甲酯衍生物的对映选择合成。在丁基锂作用下,化合物1转变成锂衍生物(2),它与醛类化合物(3)作用可得具有很高立体选择性的羰基加成物(4)。羰基化合物以C-3位异丙基的反式进入1的C-6位,即在C-6位引入(R)-构型。为避免4水解时的反醛醇缩合反应,必须对其羟基加以保护,然后才能经水解合成O-甲基-a-甲基丝氨酸衍生物(6)。用加入手征性位移试剂Eu(hfc)_3的~1H NMR谱测定了对映体过量百分数。
In this paper, L-valine as chiral auxiliary, DL-alanine as raw material, (3S, 6SR) -2,5-dimethoxy-3-isopropyl-6-methyl-3 , 6-dihydropyrazine (1) is a heterocyclic intermediate, enantioselective synthesis of (2R, 3SB) -O-methyl-a-methylserine methyl ester derivatives. Under the action of butyllithium, compound 1 is converted to lithium derivative (2), which acts on the aldehyde compound (3) to give the carbonyl adduct (4) which has a very high stereoselectivity. The carbonyl compound is translocated to the C-6 position of C-3 in the C-3 trans-position, that is, the (R) -configuration is introduced at the C-6 position. In order to avoid the reaction of the 4-hydrolysis of the reaction of the aldol condensation, the hydroxyl group must be protected before it can be hydrolyzed to synthesize the O-methyl-a-methylserine derivative (6). The% enantiomeric excess was determined by ~ 1H NMR spectroscopy with addition of the chiral shift reagent Eu (hfc) _3.