公开(公告)号：US5445963A

公开(公告)日：1995-08-29

申请号：US660830

申请日：1991-02-26

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C07B57/00 ,  C07C303/44 ,  C07C309/73 ,  C07C309/74 ,  C07C309/76 ,  C12P41/00

CPC classification number: C07B57/00 ,  C07C303/44 ,  C12P11/00 ,  C12P41/003 ,  C07B2200/07 ,  Y10S435/814 ,  Y10S435/874 ,  Y10S435/876

Abstract: A process is disclosed for the separation of an enantiomerically enriched 1-tosyloxy-2-acyloxy-3-butene and an enantiomerically enriched 1-tosyloxy-2-hydroxy-3-butene from a first mixture containing both compounds. The process includes the steps of:(a) forming a solution of the mixture in an organic solvent;(b) bringing the solution formed in (a) to a temperature wherein most of the enantiomerically enriched 1-tosyloxy-2-hydroxy-3-butene precipates, leaving in solution most of the enantiomerically enriched 1-tosyloxy-2-acyloxy-3-butene; and(c) separating the precipitate formed in (b) from the solution.

Abstract translation: 公开了从含有两种化合物的第一混合物分离对映体富集的1-甲氧基-2-酰氧基-3-丁烯和对映体富集的1-甲苯氧基-2-羟基-3-丁烯的方法。 该方法包括以下步骤：（a）在有机溶剂中形成混合物的溶液; （b）使（a）中形成的溶液达到大部分对映体富集的1-甲苯氧基-2-羟基-3-丁烯沉淀的温度，在溶液中留下大部分对映体富集的1-甲氧基-2-酰氧基-3 丁烯 和（c）将（b）中形成的沉淀物与溶液分离。

公开(公告)号：US5250743A

公开(公告)日：1993-10-05

申请号：US999240

申请日：1992-12-31

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C07C29/10 ,  C07C29/88 ,  C07C41/03 ,  C07C27/00

CPC classification number: C07C41/03 ,  C07B55/00 ,  C07C29/103 ,  C07C29/88 ,  C07D301/02 ,  C07B2200/07 ,  C07B2200/09

Abstract: In accordance with the present invention, a method for the interconvertion of the enantiomers of acyclic 1,2-dihydroxy-3-alkenes or for converting either enantiomer of acylic 1,2-dihydroxy-3-alkenes to the corresponding antipodal 1-hydroxy-2-alkoxy-3-alkene compounds has been discovered, comprising reacting in an acidic reaction media either enantiomer of an acylic vinyl epoxide (which can be derived from the corresponding acyclic 1,2-dihydroxy-3-alkene) with water, alcohol, or a mixture thereof. When substantially optically pure acyclic vinyl epoxide compounds are employed in the inventive method, the interconverted acyclic 1,2-dihydroxy-3-alkene or 1-hydroxy-2-alkoxy-3-alkene compound products are also substantially optically pure.

Abstract translation: 根据本发明，可以将非环形1,2-二羟基-3-烯烃的对映体相互转化或将酰基1,2-二羟基-3-烯烃的对映异构体转化成相应的对映体1-羟基-3-烯烃的方法， 已经发现了2-烷氧基-3-烯烃化合物，包括在酸性反应介质中使酰基乙烯基环氧化物的对映异构体（其可衍生自相应的无环1,2-二羟基-3-烯烃）与水，醇， 或其混合物。 当本发明方法中使用基本上光学纯的无环乙烯基环氧化合物时，相互转化的无环1,2-二羟基-3-烯烃或1-羟基-2-烷氧基-3-烯烃化合物产物也基本上是光学纯的。

公开(公告)号：US5236917A

公开(公告)日：1993-08-17

申请号：US793033

申请日：1991-11-15

Applicant: Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

Inventor： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

IPC: A61K31/425 ,  A61K31/415 ,  A61K31/428 ,  A61K31/47 ,  A61P29/00 ,  A61P43/00 ,  C07D275/04 ,  C07D275/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541

CPC classification number: C07D275/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541

Abstract: Novel 2-substituted saccharins which inhibit the enzymatic activity of proteolytic enzymes, are useful in the treatment of degenerative diseases and have the formula ##STR1## wherein: L is --O--, --S--, --SO-- or --SO.sub.2 --;m and n are each independently 0 or 1;R.sub.1 is halo, lower-alkanoyl, 1-oxophenalenyl, phenyl or substituted phenyl, heterocyclyl or substituted heterocyclyl or, when L is --O-- and n is 1, cycloheptatrienon-2-yl or, when L is --S-- and n is 1, cyano or lower-alkoxythiocarbonyl or, when L is --SO.sub.2 -- and n is 1, lower-alkyl or trifluoromethyl;R.sub.2 is hydrogen, lower-alkoxycarbonyl, phenyl or phenylthio; andR.sub.3 and R.sub.4 are each hydrogen or various substituents and processes for preparation and pharmaceutical compositions and method of use thereof are disclosed.

Abstract translation: 抑制蛋白水解酶的酶活性的新型2-取代糖精可用于治疗退行性疾病，并具有下式：其中：L是-O - ， - S - ， - SO-或-SO 2 - ; m和n各自独立地为0或1; R 1为卤素，低级烷酰基，1-氧代对苯二烯基，苯基或取代的苯基，杂环基或取代的杂环基，或当L为-O-并且n为1时为环庚三烯酮-2-基，或当L为-S-且n为 1，氰基或低级烷氧基硫代羰基，或当L为-SO 2 - 且n为1时，为低级烷基或三氟甲基; R2是氢，低级烷氧基羰基，苯基或苯硫基; 并且R 3和R 4各自为氢或各种取代基和制备方法，并且公开了药物组合物及其使用方法。

公开(公告)号：US6143935A

公开(公告)日：2000-11-07

申请号：US88775

申请日：1998-06-02

Applicant: Neil W. Boaz ,  M. Todd Coleman

Inventor： Neil W. Boaz ,  M. Todd Coleman

IPC: C07C49/313 ,  C07B61/00 ,  C07C45/45 ,  C07C45/72 ,  C07C49/792 ,  C07C67/00 ,  C07C67/343 ,  C07C69/716 ,  C07C319/20 ,  C07C323/22

CPC classification number: C07C319/20 ,  C07C45/455 ,  C07C67/00 ,  C07C67/343 ,  C07C2101/02

Abstract: The condensation reaction of a ketone with either an ester or a carbonate to form, respectively, a 1,3-diketone or a .beta.-ketoester often affords poor results under the standard condensation reaction conditions. High yields and high purities of the desired product can be obtained by performing the reaction using an alkoxide base in DMSO as the sole solvent.

Abstract translation: 酮与酯或碳酸酯分别形成1,3-二酮或β-酮酯的缩合反应常常在标准缩合反应条件下得到差的结果。 通过使用在DMSO中的醇盐碱作为唯一溶剂进行反应，可以获得所需产物的高收率和高纯度。

公开(公告)号：US5597841A

公开(公告)日：1997-01-28

申请号：US445118

申请日：1995-05-19

Applicant: Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Virendra Kumar ,  Chakrapani Subramanyam ,  Ranjit C. Desai ,  Dennis J. Hlasta ,  Manohar T. Saindane ,  Malcolm R. Bell ,  John J. Court ,  Robert P. Farrell

Inventor： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Virendra Kumar ,  Chakrapani Subramanyam ,  Ranjit C. Desai ,  Dennis J. Hlasta ,  Manohar T. Saindane ,  Malcolm R. Bell ,  John J. Court ,  Robert P. Farrell

IPC: C07D275/06 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07F9/6541 ,  A61K31/425

CPC classification number: C07D275/06 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07F9/6541

Abstract: 4-R.sup.4 -R.sup.5 -2-Saccharinylmethyl aryl carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R.sup.4 -R.sup.5 -2-halomethylsaccharin with an arylcarboxylic acid in the presence of an acid-acceptor.

Abstract translation: 可用于治疗退行性疾病的4-R4-R5-2-糖基甲基芳基羧酸盐通过在酸 - 受体存在下使4-R 4 -R 5 - 2-卤代甲基糖精与芳基羧酸反应来制备。

公开(公告)号：US5371074A

公开(公告)日：1994-12-06

申请号：US67637

申请日：1993-05-24

Applicant: Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

Inventor： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

IPC: A61K31/425 ,  A61K31/415 ,  A61K31/428 ,  A61K31/47 ,  A61P29/00 ,  A61P43/00 ,  C07D275/04 ,  C07D275/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541 ,  A61K31/535

CPC classification number: C07D275/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541

Abstract: Novel 2-substituted saccharins which inhibit the enzymatic activity of proteolytic enzymes, are useful in the treatment of degenerative diseases and have the formula 0010wherein:L is --O--, --S--, --SO-- or --SO.sub.2 --; m and n are each independently 0 or 1; R.sub.1 is halo, lower-alkanoyl, 1-oxophenalenyl, phenyl or substituted phenyl, heterocyclyl or substitued heterocyclyl or, when L is --O-- and n is 1, cycloheptatrienon-2-yl or, when L is --S-- and n is 1, cyano or lower-alkoxythiocarbonyl or, when L is --SO.sub.2 -- and n is 1, lower-alkyl or trifluoromethyl; R.sub.2 is hydrogen, lower-alkoxycarbonyl, phenyl or phenylthio; and R.sub.3 and R.sub.4 are each hydrogen or various substituents and processes for preparation and pharmaceutical compositions and method of use thereof are disclosed.

Abstract translation: 抑制蛋白水解酶的酶活性的新型2-取代糖精可用于治疗退行性疾病，并具有式0010其中：L是-O - ， - S - ， - SO-或-SO 2 - ; m和n各自独立地为0或1; R 1为卤素，低级烷酰基，1-氧代对苯二烯基，苯基或取代的苯基，杂环基或取代的杂环基，或当L为-O-并且n为1时，环庚三烯-2-基或当L为-S-且n为 1，氰基或低级烷氧基硫代羰基，或当L为-SO 2 - 且n为1时，为低级烷基或三氟甲基; R2是氢，低级烷氧基羰基，苯基或苯硫基; 并且R 3和R 4各自为氢或各种取代基和制备方法，并且公开了药物组合物及其使用方法。

公开(公告)号：US5126267A

公开(公告)日：1992-06-30

申请号：US660837

申请日：1991-02-26

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C07C303/44 ,  C07C309/73 ,  C07C309/74 ,  C07C309/76

CPC classification number: C07B57/00 ,  C07C303/44 ,  C12P11/00 ,  C12P41/003

Abstract: A process is disclosed for the isolation of an enantiomerically enriched alcohol from a first mixture of an enantiomerically enriched alcohol and an enantiomerically enriched ester. The process includes the steps of:(a) contacting the mixture with a reagent capable of reacting with the hydroxy function of the alcohol, without the loss of optical purity, so as to produce a second mixture containing a base stable derivative of the enantiomerically enriched alcohol and the unreacted ester;(b) contacting the second mixture with a base capable of reacting with the ester so as to produce a third mixture containing a compound more volatile than the base stable derivative of the alcohol;(c) removing the volatile compound from the third mixture; and(d) converting the base stable derivative of the alcohol back to the enantiomerically enriched alcohol, without the loss of optical purity.

Abstract translation: 公开了从对映体富集的醇和对映异构体富集的酯的第一混合物中分离对映体富集的醇的方法。 该方法包括以下步骤：（a）使混合物与能够与醇的羟基官能团反应的试剂接触，而不会损失光学纯度，从而产生含有对映体富集的碱稳定衍生物的第二混合物 醇和未反应的酯; （b）使第二混合物与能够与酯反应的碱接触，以产生含有比醇的碱稳定衍生物更易挥发的化合物的第三混合物; （c）从第三混合物中除去挥发性化合物; 和（d）将醇的碱稳定衍生物转化为对映异构体富集的醇，而不损失光学纯度。

公开(公告)号：US6162924A

公开(公告)日：2000-12-19

申请号：US290205

申请日：1999-04-09

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C07C29/64 ,  C07D233/84 ,  C07D307/20 ,  C07D233/28 ,  C07D277/04 ,  C07D301/27

CPC classification number: C07D307/20

Abstract: A process for preparing a halohydrin of a water-miscible olefin comprising: reacting a water-miscible olefin in water with a compound of the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 independently represent a branched or unbranched, substituted or unsubstituted, lower alkyl having from 1 to 5 carbons and X is a halogen, to thereby form the halohydrin of the water-miscible olefin.

Abstract translation: 一种制备水混溶性烯烃的卤代醇的方法，包括：使水中可与水混合的烯烃与水与式（I）化合物反应，其中R 1和R 2独立地表示支链或非支链的取代或未取代的低级烷基， 1至5个碳，X是卤素，从而形成水混溶性烯烃的卤代醇。

公开(公告)号：US5596012A

公开(公告)日：1997-01-21

申请号：US449152

申请日：1995-05-24

Applicant: Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

Inventor： Richard P. Dunlap ,  Neil W. Boaz ,  Albert J. Mura ,  Dennis J. Hlasta ,  Ranjit C. Desai ,  Chakrapani Subramanyam ,  Lee H. Latimer ,  Eric P. Lodge

IPC: A61K31/425 ,  A61K31/415 ,  A61K31/428 ,  A61K31/47 ,  A61P29/00 ,  A61P43/00 ,  C07D275/04 ,  C07D275/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541 ,  A61K31/50 ,  A61K31/505

CPC classification number: C07D275/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/04 ,  C07F9/6541

Abstract: Novel 2-substituted saccharins which inhibit the enzymatic activity of proteolytic enzymes, are useful in the treatment of degenerative diseases and have the formula ##STR1## wherein: L is --O--, --S--, --SO--or --SO.sub.2 --;m and n are each independently 0 or 1;R.sub.1 is halo, lower-alkanoyl, 1-oxophenalenyl, phenyl or substituted phenyl, heterocyclyl or substituted heterocyclyl or, when L is --O-- and n is 1, cycloheptatrienon-2-yl or, when L is --S-- and n is 1, cyano or lower-alkoxythiocarbonyl or, when L is --SO.sub.2 -- and n is 1, lower-alkyl or trifluoromethyl; R.sub.2 is hydrogen, lower-alkoxycarbonyl, phenyl or phenylthio; andR.sub.3 and R.sub.4 are each hydrogen or various substituents and processes for preparation and pharmaceutical compositions and method of use thereof are disclosed.

Abstract translation: 抑制蛋白水解酶的酶活性的新型2-取代糖精可用于治疗退行性疾病，并具有下式：其中：L是-O - ， - S - ， - SO-或-SO 2 - ; m和n各自独立地为0或1; R 1为卤素，低级烷酰基，1-氧代对苯二烯基，苯基或取代的苯基，杂环基或取代的杂环基，或当L为-O-并且n为1时，环庚三烯-2-基或当L为-S-且n为 1，氰基或低级烷氧基硫代羰基，或当L为-SO 2 - 且n为1时，为低级烷基或三氟甲基; R2是氢，低级烷氧基羰基，苯基或苯硫基; 并且R 3和R 4各自为氢或各种取代基和制备方法，并且公开了药物组合物及其使用方法。

公开(公告)号：US5312950A

公开(公告)日：1994-05-17

申请号：US114808

申请日：1993-08-31

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C07C69/40 ,  C07C69/80 ,  C07C303/44 ,  C07C309/73 ,  C07C303/02 ,  C07C29/74 ,  C07C69/76

CPC classification number: C07C319/28 ,  C07C29/92 ,  C07C303/44 ,  C07C41/44 ,  C07C67/60 ,  C07C69/40 ,  C07C69/80 ,  C07B2200/07 ,  C07C2101/08 ,  C07C2101/14 ,  C07C2103/74

Abstract: A method for the purification of alcohols from organic soluble impurities has been discovered comprising treating the crude alcohol with a cyclic anhydride followed by an aqueous base and extracting the corresponding half-ester into aqueous solution leaving the impurities in organic solution. This method is particularly useful for the separation of chiral, nonracemic alcohols from the corresponding antipodal ester (the mixture resulting from an enzymatic kinetic resolution) because the separation is non-chromatographic and the enantiomeric integrity of the products is maintained.

Abstract translation: 已经发现了从有机可溶性杂质中纯化醇的方法，其中包括用环状酸酐处理粗制醇，然后用碱水溶液萃取，并将相应的半酯萃取到水溶液中，留下有机溶液中的杂质。 该方法对于从相应的对映体酯（由酶动力学拆分得到的混合物）中分离手性非芳族醇是特别有用的，因为分离是非色谱法并且保持产物的对映体完整性。