L-脯氨酸催化的醛的不对称α-硫代反应

目的：对L-脯氨酸催化醛的不对称α-硫代反应进行研究。方法：以L-脯氨酸为催化剂,将正丙醛和正丁醛分别与7种硫代试剂在-40℃下反应6小时。结果：合成了14个α-硫代醛类化合物,结构经1H-NMR确证。结论：L-脯氨酸可催化醛的α-硫代反应,且产率较高,具有一定实用价值。     

非水相固定化酵母催化的(S)-2-辛醇的不对称合成

研究固定化面包酵母FD-12对不同水／有机溶剂两相体系的耐受性及不对称合成（S）-2-辛醇的还原反应。结果表明，固定化面包酵母FD-12在水／正十二烷两相体系中的耐受性最好。糖代谢活性保留值可达99.59％。不同的水／有机溶剂两相体系对生物转化影响较大。对反应条件进行优化，在水／正十二烷相体积比为20／5，固定化细胞用量为15．0g，初始底物2-辛酮浓度为200mmol／L的条件下转化96h，（S）-2-辛醇产物得率可达29．59％，ee（S）值达98．81％。     

脯氨酸催化酮的不对称α－硫代反应

本文主要对脯氨酸催化酮的不对称α-硫代反应进行了研究,考察了3种环酮、7种硫代试剂、4种溶剂和不同温度对反应活性、产率以及对映体过量值(ee)的影响.在极性大的溶剂DMF、DMSO中,都取得了90%左右的高产率,温度低至-40℃时,ee值提高到20%;硫代试剂上为供电子基可进一步提高ee值.文献报道了的小分子催化酮的直接α-硫代反应比较少,用脯氨酸作为催化剂不仅得到了很好的产率,也能实现酮的不对称硫代反应.     

萘普生的催化不对称合成

按反就类型介绍了近几年来催化不对称合成非甾体消炎镇痛药萘普生的各种新方法。     

酵母菌DM10不对称合成(R)-(-)邻氯扁桃酸甲酯

目的合成(S)-氯吡咯雷的关键中间体——(R)-(-)邻氯扁桃酸甲酯,并建立了优化的还原条件。方法以邻氯苯乙酮酸甲酯为底物,利用酵母菌DM10的醇脱氢酶及其辅酶合成(R)-(-)邻氯扁桃酸甲酯,并考察了底物质量浓度、初始pH、转化温度和反应时间对不对称还原的影响。结果和结论获得优化的还原条件:接种量体积分数为10%,初始pH值为6.5,底物质量浓度为1 g.L-1,温度为30℃,转化36 h,转化率为98.75%,产率为82.25%,对映体过量值为95.1%。     

不对称转换法合成D—脯氨酸

用不对称转称的方法,以（2R,3R）－酒石酸为拆分剂,在丁醛存在下,使L－脯氨酸的消旋及D－脯氨酸与（2R,3R）－酒石酸的成盐结晶两步反应同时进行,总收率达82％。     

催化不对称合成法在手性药物合成中的应用

结合实例就催化不对称合成的两种方法应用于手性药物合成作简要概述。外消旋体拆分、化学计量不对称合成和催化不对称合成是利用化学手段获得手性药物的 3种方法 ,其中催化不对称合成法是最经济有效地合成手性药物的方法 ,它又可分为化学催化不对称合成法和酶催化不对称法。     

L-(-)-肉碱的合成

以自制手性salen-Co^Ⅲ为催化剂，水解动力学拆分外消旋环氧氯丙烷，得到高光学纯度的（S）-（＋）-环氧氯丙烷，再经季胺化、氰化、水解及离子交换制得L-（-）-肉碱，总收率70％[以（S）-（＋）-环氧氯丙烷计]。     

不对称亨利反应在(R)-沙美特罗合成中的应用

目的 使用不对称亨利反应合成沙美特罗。方法 以4-苯基丁醇为起始原料合成长链脂肪醛,同时由对羟基苯甲醛出发经3步反应制备前手性苯甲醛,继而通过不对称亨利反应制得手性硝基醇化合物,随后用氢化方法合成(R)-沙美特罗。结果与结论 通过不对称亨利反应制得硝基醇化合物,产物的对映选择性较好(60% ee),新路线省去了原文献中制备三级胺和脱苄基两步反应,合成路线未见报道。     

不对称氢化、氢转移反应制备(R)-邻氯扁桃酸甲酯：(S)-氯吡格雷关键中间体的不对称合成

目的 用不对称氢化、氢转移方法制备合成(S)-氯吡格雷的关键中间体——(R)-邻氯扁桃酸甲酯。方法 以α-邻氯扁桃酮酸甲酯为起始原料,分别用不对称氢化和氢转移方法制备(R)-邻氯扁桃酸甲酯。结果与结论 使用不对称氢化方法制备(R)-邻氯扁桃酸甲酯,对映选择性为64.8% ,用氢转移方法,优化催化条件后目标产物的ee值高达92.6%,从而为(S)-氯吡格雷的不对称合成奠定了基础。     

(-)和(+)棉酚对雄大鼠生育力的影响

棉酚有明显的抗雄性生育作用,但在理论上尚不清楚消旋棉酚的抗生育作用和毒性来自那一种光学异构体。已有报告指出(+)棉酚无毒无效。但对(-)棉酚的研究迄今尚未有报道。本文应用本所合成室制备之(+)和(-)棉酚,观察了他们的抗生育作用。实验用Wistar雄大鼠(190～220g)25只,分为对照,(+)棉酚30mg/kg,(-)棉酚15和30 mg/kg以及消旋棉酚30 mg/kg等5组。每天喂药1次,(+)棉酚和(-)棉酚     

(S)-(+)-2,2-二甲基环丙烷甲酰胺的合成

甘氨酸乙酯盐酸盐经重氮化反应制得重氮乙酸乙酯,与异丁烯在自制的手性催化剂—(R,R)-(+)-2,2′-亚异丙基双(4-叔丁基-2-噁唑啉)与三氟甲磺酸亚铜的络合物催化下进行不对称环丙烷化反应,制得(S)-2,2-二甲基环丙烷甲酸乙酯,碱性条件下水解,再与氯化亚砜反应得酰氯后氨解制得(S)-(+)-2,2-二甲基环丙烷甲酰胺,总收率约27%。     

Effects of intrahypothalamic 6-hydroxydopamine on central thermoregulatory responses to (+)- and (-)-norepinephrine and dopamine

Tntracerebral injection of 0.01 or 0.015 to 0.1 μmol of both the (+)- and (-)- cnantiomers of norepinephrine (NE) and dopamine (DA) into the preoptic-anterior hypothalamic region (PO/AH) of awake cats caused dose-related depressions of rectal temperature. After local denervation of the preoptic-anterior hypothalamic region (PO/AH) with 6-hydroxydopamine (6-OHDA), hypothermie receptor sensitivity to (-)-NE increased (supersensitivity) whereas sensitivity to (+)-NE remained virtually unchanged and that to DA decreased (subsensitivity). These demonstrations of central pharmacologie (hypothermie) receptor supersensitivity and stereoselectivity are qualitatively similar to pharmacological drug-receptor interactions observed in peripheral adrenergic neuroeffector tissues. Drug-induced reductions in rectal temperature were accompanied by physiologically and temporally related reductions in heart rate, in shivering and. less regularly, by peripheral vasodilation. The differential responses to DA. (+)- and (-)-NE are discussed in relationship to their possible modes of hypothermie receptor interaction.     

(-)和(+)棉酚对雄大鼠生育力的影响

Racemic, (-) and (+) gossypol, provided by the Department of Organic Chemistry of our institute, was suspended in 2.5% tween 80 solution. Adult male Wistar rats 190～220 g in weight were allotted to 5 groups. Animals in group 1 received 2.5% tween 80 solution as control. Rats in group 2 were treated with racemic gossypol at the dosage of 30 mg/kg for 2 weeks. Animals in group 3 and 4 were given 15 mg/kg of (-) gossypol for 2 weeks and 30 mg/kg of (-) gossypol for 1 week respectively. Rats in group 5 were treated with (+) gossypol at the dosage of 30 mg/kg for 2 weeks.Four weeks from the beginning of gossypol treatment the rats were cohabited with adult females for 7 days. Then the motility of the sperms in the cauda epididymides was estimated The female rats were examined for pregnancy 7 days later.Treatment with (-) gossypol at 30 mg/kg caused significant decreases in body weight of the rats (P<0.05). One of the five rats died 7 days after the last administration, while (+) gossypol and racemic gossypol at the dosage employed had no effect on the body weight. (+) Gossypol at 30 mg/kg for 2 weeks had no effect on the motility of the sperms in the cauda epididymides and no effect on the fertility of the animals: nor was there any effect on the weights of the testis, epididymis, prostate and seminal vesicle. The sperms of the cauda epididymides were found to be dead in the groups treated with 15 and 30 mg/kg of (-)gossypol. Raccmic gossypol given for 2 weeks at 30 mg/kg caused loss of fertility of the male rats which confirmed our previous findings.(?)t may be postulated that (+) gossypol has no antifertility effect nor toxicity at the dosage employed. (-) Gossypol is the active stereoisomer of racemic gossypol.     

Comparative Brain Exposure to (-)-Carbovir After (-)-Carbovir or (-)-6-Aminocarbovir Intravenous Infusion in Rats

Purpose. Evaluate the ability of (-)-6-aminocarbovir ((-)-6AC) to improve the CNS exposure to (-)-carbovir ((-)-CBV). Methods. Activation of (-)-6AC in vitro was assessed by incubations of rat brain tissue homogenates. The in vivo brain exposure to (-)-CBV was then examined in rats after iv infusions of either (-)-CBV (n = 4) or (-)-6AC (n = 5). The drugs were infused to steady-state via the jugular vein. At the end of the infusion, a bolus of [³H]inulin was injected via the femoral vein in order to obtain an estimate of the brain vascular space. Results. (-)-6AC was converted to (-)-CBV by incubations of rat brain tissue homogenates. After iv infusion of (-)-CBV, the brain/ blood concentration ratio of (-)-CBV was 0.032 ± 0.009. The brain/ blood concentration ratio of (-)-CBV after iv infusion of (-)-6AC was 0.080 ± 0.020. Conclusions. (-)-6AC improved the brain delivery of (-)-CBV, although the absolute exposure of the brain tissue to (-)-CBV was still quite low.     

HPLC测定(S)-4-苯基-2-噁唑烷酮的纯度

目的采用HPLC法测定(S)-4-苯基-2-噁唑烷酮(SPO)的纯度。方法采用Welchrom C18色谱柱,流动相为0.02 mol·L-1磷酸二氢钾(KOH调p H5)-乙腈(60∶40),检测波长210 nm,流速1.0 m L·min-1,柱温35℃。结果 SPO0.3036~6.072μg·m L-1与峰面积的线性关系良好(r=0.9999),检测限和定量限分别为0.9099、3.033 ng。结论所用方法准确、灵敏、快速,适用于检测SPO中的微量杂质。     

盐酸帕罗西汀的合成

目的:合成盐酸帕罗西汀。方法:以(±)-trans-4-(4-氟苯基)-3-羟甲基-1-甲基哌啶为原料经手性拆分、酯化、醚化、甲酰化、水解5步反应合成(-)-盐酸帕罗西汀。结果:合成了帕罗西汀,总收率41．2％。结论:本方法可以方便地合成帕罗西汀,操作简便,提高了收率,缩短了反应时间。     

Concise stereoselective total synthesis of (+)-muricatacin and (+)-epi-muricatacin

Efficient stereoselective total synthesis of (+)-muricatacin (1) and (+)-epi-muricatacin (8) was accomplished from commercially available chemical pent-4-ynoic acid via Shi's asymmetric epoxidation and Mitsunobu reaction as the key steps in 17.8% and 26.9% overall yields, respectively.     

Total synthesis and biological evaluation of (+)- and (-)-Butyl ester of rosmarinic acid

An efficient method for the synthesis of the natural product (+)-(R)-butyl ester of rosmarinic acid (+)-(R)-1 and its enantiomer ( - )-(S)-1 has been developed by chemical resolution of its phenyl lactic acid precursors 4 with ( - )-menthol. Their antioxidative and anti-tumor activities were evaluated.     

西司他丁中间体(+)-(S)-2,2-二甲基环丙羧酸的合成

目的:合成( )-(S)-2,2-二甲基环丙羧酸.方法:以2,2-二甲基环氧乙烷和三乙基膦醋酸酯为原料,经Witting环化生成三元环制备外消旋2,2-二甲基环丙羧酸,用L-(-)-薄荷醇为拆分试剂拆分得到光学活性目标化合物.结果:成功合成出( )-(S)-2,2-二甲基环丙羧酸,拆分收率提高到26.8%.结论:此方法操作简便,成本较低,收率较高,适于大量生产.