公开(公告)号：US5306638A

公开(公告)日：1994-04-26

申请号：US854944

申请日：1992-03-20

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C12P11/00 ,  C12P41/00 ,  C12R1/38

CPC classification number: C12P11/00 ,  C12P41/004 ,  Y10S435/874 ,  Y10S435/876

Abstract: A process has been developed for the enzymatic esterification of 1,2-diol monosulfonates comprising contacting an ester; a 1,2-diol monosulfonate; an enzyme derived from a microorganism or animal organ which has stereoselective activity to asymmetrically esterify said 1,2-diol monosulfonate; in the presence of a nonhydroxylic organic solvent and an amine additive of the general formula R.sup.3.sub.2 R.sup.4 N, whereinR.sup.3 may be the same or different and is selected from hydrogen or a straight or branched C.sub.1 -C.sub.20 alkyl; andR.sup.4 is a straight or branched C.sub.1 -C.sub.20 alkyl; or an unsubstituted or substituted C.sub.3 -C.sub.20 aryl or heteroaryl group (with saisd substituent selected from C.sub.1 -C.sub.4 alkyl, halogen, or C.sub.1 -C.sub.4 alkoxy, and said hetero atom selected from nitrogen, sulfur, or oxygen);to produce a mixture of enantiomerically enriched unreacted 1,2-diol monosulfonate and the corresponding antipodal enantiomerically enriched ester. The resulting enantiomerically enriched products are useful chemical intermediates that may be employed in the synthesis of pharmaceutical and agricultural chemicals.

Abstract translation: 已经开发了用于1,2-二醇单磺酸酯酶促酯化的方法，包括使酯接触; 1,2-二醇单磺酸盐; 来源于微生物或动物器官的酶具有立体选择性活性以使所述1,2-二醇单磺酸盐不对称酯化; 在非羟基有机溶剂和通式R32R4N的胺添加剂的存在下，其中R 3可以相同或不同，并且选自氢或直链或支链C 1 -C 20烷基; 且R 4为直链或支链C 1 -C 20烷基; 或未取代或取代的C 3 -C 20芳基或杂芳基（具有选自C 1 -C 4烷基，卤素或C 1 -C 4烷氧基的所述取代基，所述选自氮，硫或氧的杂原子）。 以产生对映体富集的未反应的1,2-二醇单磺酸盐和相应的对映体对映异构体富集的酯的混合物。 所得到的对映体富集的产物是可用于合成药物和农业化学品的有用的化学中间体。

公开(公告)号：US5250696A

公开(公告)日：1993-10-05

申请号：US860340

申请日：1992-03-30

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

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

IPC: C07D275/06 ,  C07D417/04 ,  C07D417/12 ,  C07F9/6541

CPC classification number: C07D275/06 ,  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：US4921798A

公开(公告)日：1990-05-01

申请号：US412260

申请日：1989-09-25

Applicant: Neil W. Boaz

Inventor： Neil W. Boaz

IPC: C12P7/42 ,  C12P41/00 ,  C12R1/39

CPC classification number: C12P7/42 ,  C12P41/005 ,  Y10S435/876

Abstract: R- and S-1-Phenyl-1,3-propanediol, each of high optical purity, were prepared by a chemoenzymatic sequence starting with ethyl benzoylacetate. The first step was a catalytic hydrogenation of the .beta.-ketoester conducted at room temperature. The enzymatic hydrolysis of the resulting hydroxyester proceeded in a facile manner using a commercial preparation of the lipase from Pseudomonas fluorescens. The enzymatic hydrolysis proceeded at a moderate rate (350 mg lipase/0.10 mol of racemic ester required a 20-hour reaction time with an enantiomeric rate ratio (E value) of 36). The hydrolysis was run to 45-50% conversion to afford isolated S-3-phenyl-3-hydroxypropionic acid of 85-90% ee after separation from the residual ester (aqueous base extraction). The optical purity of the hydroxy acid was determined by conversion to the methyl ester (CH.sub.3 I, KHCO.sub.3, acetone), and derivatization with S-MTPA-Cl, and .sup.1 H NMR analysis. A single recrystallization of the isolated acid afforded optically pure (>98% ee) S-3-phenyl-3-hydroxypropionic acid in an overall 36% yield from the racemic ester. The acid was reduced with borane in THF to afford optically purs S-diol in 97% yield after crystallization. The overall sequence proceeded in 34% total yield from racemic ester with an additional 45-55% recovered as the antipodal ester. This antipodal ester is obtained in 85-95% ee, and the corresponding hydroxy-acid was readily obtained (NaOH), CH.sub.3 OH/H.sub.2 O) and recrystallized to optical purity. Reduction then afforded R-1-phenyl-1,3-propanediol in 30% to overall yield from racemic ester.

Abstract translation: 通过以苯甲酰乙酸乙酯开始的化学酶序列制备各自具有高光学纯度的R-和S-1-苯基-1,3-丙二醇。 第一步是在室温下进行的β-酮酯的催化氢化。 所得羟基酯的酶水解以易于使用的荧光假单胞菌的脂肪酶的商业制剂进行。 酶水解以中等速率进行（350mg脂肪酶/ 0.10mol外消旋酯需要20小时反应时间，对映体速率比（E值）为36）。 水解进行45-50％转化，从分离残留酯（水性碱提取）后得到85-90％ee的分离的S-3-苯基-3-羟基丙酸。 羟基酸的光学纯度通过转化成甲酯（CH 3 I，KHCO 3，丙酮）和用S-MTPA-Cl衍生化和1 H NMR分析来测定。 分离的酸的单次重结晶得到光滑纯的（> 98％ee）S-3-苯基-3-羟基丙酸，总共36％的产率来自外消旋酯。 用硼烷在THF中将酸还原，得到结晶后的产率为97％的光学式S-二醇。 总体序列以外消旋酯的总收率为34％，另外作为对映体酯回收45-55％。 在85-95％ee中得到该对映体酯，容易得到相应的羟基酸（NaOH），CH 3 OH / H 2 O）并重结晶至光学纯度。 然后还原，得到30％的R-1-苯基-1,3-丙二醇，得自外消旋酯的总产率。