Method for producing chiral mercapto amino acids

    公开(公告)号:US20070112216A1

    公开(公告)日:2007-05-17

    申请号:US10581790

    申请日:2004-11-15

    IPC分类号: C07C323/29

    摘要: The invention relates to a method for producing chiral mercapto amino acids of formula (I) wherein R1, R2 and R3 can represent hydrogen, C6-C12 aryl, C1-C6-alkyl-C6-C12-aryl, C6-C12-aryl-C1-C6-alkyl, C1-C18-alkyl or C2-C18-alkenyl, R2 and R3 forming a saturated or unsaturated ring. According to said method, a) an oxo compound of formula (II), wherein X represents a leaving group, is reacted in the presence of ammonia or ammonium hydroxide and a sulfide, optionally under phase transfer catalysis or addition of a solubiliser, with a ketone or an aldehyde of formula (III) wherein R4 and R5 can represent a C1-C12 alkyl radical or a C6-C20 aryl radical or one of the two radicals H, or R4 and R5 together form a C4-C7 ring, to form the compound of formula (IV), that b) reacts with HCN to form the corresponding nitrile, whereupon c) the crystallised nitrile is converted, by selective hydrolysis by means of a mineral acid, into the corresponding amide of formula (VI), and d) is then converted into the corresponding chiral amide of formula (VI*) by means of an L amidase or a chiral dissociating acid, whereupon by reaction with an acid, the desired chiral mercapto amino acid of formula (I) is obtained, or e) first the reaction with an acid is carried out, and then the conversion into the chiral mercapto amino acid takes place.

    Process for the preparation of chiral &agr;-hydroxycarboxylic acids
    2.
    发明授权
    Process for the preparation of chiral &agr;-hydroxycarboxylic acids 失效
    制备手性α-羟基羧酸的方法

    公开(公告)号:US06818423B2

    公开(公告)日:2004-11-16

    申请号:US10286892

    申请日:2002-11-04

    IPC分类号: C12P742

    摘要: A process for the preparation of chiral &agr;-hydroxycarboxylic acids: in which R1 is optionally halogen substituted C1-C2-alkyl and R2 is optionally halogen substituted C2-C3-alkyl from a compound: in which R′2 is optionally halogen substituted C2-C3-alkylene, m is 0 or 1 and R is optionally substituted alkyl, aryl, heteroaryl or heterocyclyl and X can be oxygen, sulfur, sulfinyl, sulfonyl, imino, C1-C6-alkylimino, xanthate, silyl, or, if m is equal to 0, halogen, which is reacted in the presence of a cyanide group donor to give the corresponding (R)- or (S)-cyanohydrin or its racemate: which then is converted by means of acidic hydrolysis into an acid: or its racemate, and by cleavage of the group: (R)m-X  (V), and optional resolution, whereby the desired chiral &agr;-hydroxycarboxylic acid of the formula (I) is obtained.

    摘要翻译: 一种制备手性α-羟基羧酸的方法:其中R 1任选为卤素取代的C 1 -C 2 - 烷基,R 2为卤素取代的C 2 -C 3 - 烷基,其中R'2任选为卤素取代的C2- C3-亚烷基,m是0或1,R是任选取代的烷基,芳基,杂芳基或杂环基,X可以是氧,硫,亚磺酰基,磺酰基,亚氨基,C 1 -C 6烷基亚氨基,黄原酸酯,甲硅烷基,或者,如果m是 等于0,卤素,其在氰化物基团供体的存在下反应,得到相应的(R) - 或(S) - 氰基氢茚或其外消旋物,然后通过酸性水解转化成酸:或其 通过裂解所述基团:任选的分辨率,由此获得所需的式(I)手性α-羟基羧酸。

    Process for preparing heterocyclic (R)- and (S)-cyanohydrins
    3.
    发明授权
    Process for preparing heterocyclic (R)- and (S)-cyanohydrins 失效
    制备杂环(R) - 和(S) - 氰基醇的方法

    公开(公告)号:US07052885B2

    公开(公告)日:2006-05-30

    申请号:US10325922

    申请日:2002-12-23

    摘要: A process for preparing enantiomer-enriched heterocyclic (R)- and (S)-cyanohydrins of the formula (I), where R1, R2, R3, R4 independently of one another are H, an unsubstituted or substituted C1–C24-alkyl, alkenyl or alkynyl radical, where one or more carbon atoms in the chain can be replaced by an oxygen atom, a nitrogen atom, a sulfur atom, an SO or an SO2 group, an unsubstituted or substituted aryl or heteroaryl radical or heterocyclic radical or halogen, hydroxyl, NR5R6, acetyl, oxo, C1–C6-carbalkoxy, C1–C6-carbalkoxyamino, COOR7, cyano, amide, benzoylamino or NO2,R5 and R6 are H, C1–C6-alkyl radical, phenyl radical, benzyl radical or COOR7, or together form a C2–C8-alkylene or heteroalkylene radical,R7 is H or C1–C6-alkyl,n is 0, 1, 2 or 3,X, Y and Z can be an unsubstituted or substituted carbon atom or a radical selected from the group consisting of N, O, S or NR5R6, where R5 and R6 are as defined above, SO or SO2, and at least one of the radicals X, Y and Z is not a carbon atom, where the compounds of the formula (I) can have one or more double bonds in the ring, with the proviso that in a 5-membered ring the double bond is not conjugated with the —C(OH)CN-group, and/or can be anellated and/or bridged,by reacting a ketone of the formula (II), where R1, R2, R3, R4, X, Y, Z and n have the meanings above, with an (R)- or (S)-hydroxynitrile lyase in an organic, aqueous or two-phase system, or in emulsion, in the presence of a cyanide group donor.

    摘要翻译: 制备式(I)的对映异构体富集的杂环(R) - 和(S) - 氰基醇的方法,其中R 1,R 2,R 3,R 4彼此独立地是H,未取代或取代的C 1 - 链烯基或炔基,其中链中的一个或多个碳原子可以被氧原子,氮原子,硫原子,SO或 SO 2 2基团,未取代或取代的芳基或杂芳基或杂环基或卤素,羟基,NR 5 R 6,乙酰基,氧代C 1 -C 6 - 亚烷基氧基,C 1 -C 6 - 烷氧基氨基,COOR 7,氰基,酰胺,苯甲酰氨基或NO 2,R 5和R 6是H C 1 -C 6 - 烷基,苯基,苄基或COOR 7,或一起形成C 1 -C 6 - 8亚烷基或杂亚烷基,R 7是H或C 1 -C 6 - 烷基,n是0,1,2或3,X,Y 并且Z可以是未取代或取代的碳原子或选自它的基团 由N,O,S或NR5R6组成的基团,其中R 5和R 6如上定义,SO或SO 2,并且基团X,Y和Z中的至少一个不是碳 原子,其中式(I)的化合物可以在环中具有一个或多个双键,条件是在5元环中双键不与-C(OH)CN-基团共轭,并且 /或可以通过使式(II)的酮(其中R 1,R 2,R 3,R 4,X,Y,Z和n具有上述含义)与(R) - 或( S) - 羟基腈裂解酶在有机,水相或两相体系中,或在乳液中,在氰化物基团给体存在下。

    Process for preparing protected, enantiomer-enriched cyanohydrins by in-situ derivatization
    4.
    发明授权
    Process for preparing protected, enantiomer-enriched cyanohydrins by in-situ derivatization 失效
    通过原位衍生制备保护的富含对映异构体的氰醇的方法

    公开(公告)号:US06909011B2

    公开(公告)日:2005-06-21

    申请号:US10325923

    申请日:2002-12-23

    CPC分类号: C12P13/004

    摘要: A process for preparing protected, enantiomer-enriched cyanohydrins of the formula where R1 and R2 independently of one another can be an unsubstituted, monosubstituted or polysubstituted C1-C20-alkyl, C5-C20-aryl, C5-C20-heteroaryl, C5-C20-alkaryl, C5-C20-alkylheteroaryl or C5-C20-aralkyl radical or an unsubstituted, monosubstituted or polysubstituted C5-C20-heterocycle, or C5-C20-alkylheterocycle or together can be an unsubstituted or substituted C4-C20-alkylene radical, which can contain one or more heteroatoms in the chain, or one of the radicals is hydrogen, and R3 can be an unsubstituted or substituted C1-C20-alkyl, C5-C20-aryl or C5-C20-heteroaryl radical, by reacting an aldehyde or ketone of the formula where R1 and R2 are defined as above, in the presence of an (R)- or (S)-hydroxynitrile lyase in an organic, aqueous or 2-phase system or in emulsion at a temperature of −5 to +40° C. with a carbonic ester nitrile of the formula where R3 is defined as above.

    摘要翻译: 制备具有下式的受保护的对映异构体富含氰醇的方法其中R 1和R 2彼此独立地可以是未取代的,单取代的或多取代的C 1 -C 20 - 烷基 C 5 -C 20 - 芳基,C 5 -C 20 - 杂芳基,C 5 - C 20 -C 20 - 烷芳基,C 5 -C 20 - 烷基杂芳基或C 5 -C 或是未取代的单取代或多取代的C 5 -C 20 - 杂环或C 5 - -C 20 - 烷基杂环或一起可以是未取代或取代的C 4 -C 20 - 亚烷基,其可以含有一个或多个杂原子 在链中,或者一个基团是氢,并且R 3可以是未取代或取代的C 1 -C 20 - 烷基,C 5 C 20 -C 20 - 芳基或C 5 -C 20 - 杂芳基,通过使下式的醛或酮反应其中R1和R2 在有机,水相或两相体系中的(R) - 或(S) - 羟基腈裂解酶存在下,或在-5至+ 40℃的温度下与碳酸酯 腈,其中R3如上定义。

    Process for preparing enantiomer-enriched amino- and hydroxyfuranones
    5.
    发明授权
    Process for preparing enantiomer-enriched amino- and hydroxyfuranones 失效
    制备富含对映异构体的氨基和羟基呋喃酮的方法

    公开(公告)号:US06417377B1

    公开(公告)日:2002-07-09

    申请号:US10044908

    申请日:2002-01-15

    IPC分类号: C07D30760

    CPC分类号: C07D307/60 C07D307/66

    摘要: A process for the preparation of enantiomer-enriched aminofuranones and hydroxyfuranones in which an enantiomer-enriched cyanohydrin is acylated by an acylating agent, then cyclized at 40 to 90° C. in the presence of zinc or a zinc compound to the corresponding enantiomer-enriched aminofuranone, which is converted where appropriate by acid hydrolysis into the corresponding enantiomer-enriched hydroxyfuranone.

    摘要翻译: 制备富含对映异构体的氨基呋喃酮和羟基呋喃酮的方法,其中富含对映异构体的氰醇被酰化剂酰化,然后在锌或锌化合物的存在下在40至90℃下环化成相应的对映体富集 氨基呋喃酮,其通过酸水解适当地转化成相应的富含对映异构体的羟基呋喃酮。

    Increased enantioselectivity of lipase catalyzed transesterification of
alkynols with vinyl esters
    6.
    发明授权
    Increased enantioselectivity of lipase catalyzed transesterification of alkynols with vinyl esters 失效
    脂肪酶催化的炔基酯与乙烯基酯的酯交换增加了对映选择性

    公开(公告)号:US5639662A

    公开(公告)日:1997-06-17

    申请号:US529712

    申请日:1995-09-18

    IPC分类号: C12P41/00

    CPC分类号: C12P41/004

    摘要: Process for enhancement of enantioselectivity in the enzymatic separation of (R)- and (S)-enantiomers of an asymmetric alkynol, a lipase and in the presence of at least one vinyl ester, in which the acid component has at least 4 C atoms, an organic solvent and with the addition of water. Also disclosed is a process for enhancement of enantioselectivity in the enzymatic separation of (R)- and (S)-enantiomers of an alcohol with the aid of the abovementioned vinyl ester under addition of a second vinyl ester having at least 2 C atoms less in the alkyl chain than the vinyl ester used as esterifying agent.

    摘要翻译: 用于增强不对称炔醇,脂肪酶和至少一种乙烯基酯的(R) - 和(S) - 对映异构体的酶分离中的对映体选择性的方法,其中酸组分具有至少4个C原子, 有机溶剂和加入水。 还公开了一种通过在上述乙烯基酯的帮助下,在加入具有至少2个C原子的第二乙烯基酯的情况下,在醇的(R) - 和(S) - 对映体的酶分离中增强对映体选择性的方法 烷基链比乙烯基酯用作酯化剂。