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    Process for the enantioselective synthesis of hydroxypyrrolidines from amino acids and products thereof
    1.
    发明授权
    Process for the enantioselective synthesis of hydroxypyrrolidines from amino acids and products thereof 失效
    从氨基酸及其产物对映选择性合成羟基吡咯烷的方法

    公开(公告)号：US5801247A

    公开(公告)日：1998-09-01

    申请号：US787994

    申请日：1997-01-23

    申请人： David R. Dalton ,  Yifang Huang

    发明人： David R. Dalton ,  Yifang Huang

    IPC分类号： C07D207/12 ,  C07D207/26 ,  C07D207/273 ,  C07D263/10 ,  C07D263/14

    CPC分类号： C07D207/273 ,  C07D207/12 ,  C07D263/10

    摘要： The present invention relates to processes for the enantioselective synthesis of hydroxypyrrolidines from amino acids. An amino methyl ester is used as the starting material. The ester is reacted with a benziminoethyl ether to produce an oxazoline or thiazoline. Specifically, L-serine methyl ester is used to produce 4-(carbomethoxy)-2-phenyl-.increment..sup.2 -oxazoline, and cysteine is used to produce the corresponding thiazoline. The oxazoline (or thiazoline) can be reduced to an aldehyde by treatment with a slight excess of DIBAL-H. The oxazoline is quenched with alcohol and reacted with (carbomethoxymethylene)triphenylphosphorane, to produce (S)-(+)-methyl (E)- and (S)-(-)-methyl (Z)-3-(4,5-dihydro-2-phenyl-4-oxazolyl)-2-propenoate. The double bond is hydroxylated to yield the diol esters. The resulting diol is then treated with aqueous acid to hydrolyze the oxazoline and recyclize to produce 3,4-dihydroxy-5-hydroxymethylpyrrolidone benzoate. This is treated with an excess of borane in tetrahydrofuran to yield (2-hydroxymethyl) 3,4-dihydroxypyrrolidine. The intermediate compounds are useful both in the present process and as final products themselves. The total yield of the mixture of isomers, as well as their ratio, can be varied.

    摘要翻译： 本发明涉及从氨基酸对映选择性合成羟基吡咯烷的方法。 使用氨基甲酯作为原料。 酯与苯甲亚乙基醚反应生成恶唑啉或噻唑啉。 具体地说，使用L-丝氨酸甲酯来制备4-（甲酯基）-2-苯基-2H-恶唑啉，半胱氨酸用于制备相应的噻唑啉。 恶唑啉（或噻唑啉）可以通过用稍微过量的DIBAL-H处理而还原成醛。 恶唑啉用醇淬灭并与（甲酯基亚甲基）三苯基正膦反应生成（S） - （+） - 甲基（E） - 和（S） - （ - ） - 甲基（Z）-3- 二氢-2-苯基-4-恶唑基）-2-丙烯酸甲酯。 羟基化双键得到二醇酯。 然后将所得二醇用酸水溶液处理以水解恶唑啉并再循环以产生3,4-二羟基-5-羟甲基吡咯烷酮苯甲酸酯。 在四氢呋喃中用过量的硼烷处理，得到（2-羟甲基）3,4-二羟基吡咯烷。 中间体化合物在本方法中可用作最终产物本身。 异构体混合物的总产率及其比例可以变化。