Enantioselective synthesis of the tetrahydrofuran lignans (-)- and (+)-magnolone

The optically pure trisubstituted 7'-oxotetrahydrofuran lignans (-)- and (+)-magnolone ( 1) were synthesized by employing stereoselective S N1 intramolecular cyclization as a key reaction. The absolute configuration of naturally occurring (-)-magnolone was determined as (7 S,8 R,8' S).     

Stereoselective synthesis of (+)-11betaH,13-dihydroestafiatin, (+)-11betaH,13-dihydroludartin, (-)-compressanolide,and (-)-11betaH,13-dihydromicheliolide from santonin

Starting from 2 and 3, obtained from santonin (1), we have synthesized natural guaianolides 4-7. Chemoselective epoxidation of 2 gave (+)-11betaH,13-dihydroestafiatin (4), and epoxidation of 3 followed by regioselective elimination of the hydroxyl group afforded (+)-11betaH,13-dihydroludartin (5). Sharpless' mild regioselective ring-opening of 4 and 5 followed by hydrogenolysis yielded (-)-compressanolide (6) and (-)-11betaH,13-dihydromicheliolide (7), respectively.     

Effect of (+/-)-, (+)- and (-)-gossypol on the lactate dehydrogenase-X activity of rat testis

The effect of (+/-)-, (+)- and (-)-gossypol on testicular lactate dehydrogenase-X (LDH-X) was studied in vitro and in vivo. It was found that racemic gossypol and the two optical enantiomers had similar inhibitory effects on rat testicular LDH-X in vitro. However, neither racemic gossypol nor the enantiomers exhibited an inhibitory effect on testicular LDH-X in vivo. It is concluded that inhibition of testicular LDH-X is not likely to be the mechanism of the antifertility action of gossypol. The inhibition of testicular LDH-X in vitro by all three preparations of gossypol is probably non-specific.     

(+)-伪麻黄碱向(-)-麻黄碱的转化

目的：研究用“一步法”由（＋）－伪麻黄碱向（－）－麻黄碱的转化 。方法：加入等摩尔量的乙肝作催进剂,以冰醋酸为溶剂,回流反应１．５－４h。结果：（＋）－的麻黄碱以８０％－８５％的产率转化为（－）－麻黄碱。结论 本方法步骤少,操作简单,时间短,转化率高,后处理简便,成本低,易于工业在生产,具有良好的经济效益和社会效益。     

Effect of (-)- and (+)-gossypol on fertility in male rats

(+)-Gossypol has neither antifertility effect nor toxicity at the dosage of 30 mg/kg orally for 14 days in male rats, but slight damage was found in the germinal epithelium of the testis in animals dosed for 4 weeks. (-)-Gossypol at 30 mg/kg orally for 7 days clearly had an antifertility effect in male rats. It appears that (-)-gossypol is the active stereoisomer of racemic gossypol.     

Enantioselective synthesis of (-)-dendroprimine and isomers

An enantioselective and diastereoselective synthesis of six 5,7-dimethylindolizidine isomers is described via an intramolecular cyclization that involves an allylsilyl nucleophilic group and an acyliminium ion. The first total synthesis of naturally occurring (-)-dendroprimine has been achieved in five steps.     

Probing into the mechanism of action, metabolism and toxicity of gossypol by studying its (+)- and (-)-stereoisomers

The chemistry of gossypol is very relevant to its unique actions. The two aldehyde groups can easily bind to proteins via aldehyde-amino group linkage. Gossypolone, the in vivo oxidation product of gossypol, may form a redox system with its corresponding hemiquinone, leading to free radical generation. There are marked differences in the disposition and metabolism between (+)- and (-)-gossypol. The elimination half life of (+)-gossypol was much longer than that of (-)-gossypol. The higher rate of elimination of (-)-gossypol may be due to its lower rate of binding to tissue proteins, since the Vd of (-)-gossypol was much smaller than that of the (+)-isomer. A single intratesticular injection of 200 micrograms of (-)-gossypol caused a 70.4% decrease of the sperm count along with marked atrophy of the testes. However, neither a significant decrease in sperm count nor atrophy of the testes was observed after a similar injection of (+)-gossypol, suggesting that there is a strict stereochemical requirement for the interaction between gossypol and the testicular target molecules. Racemic gossypol stimulated superoxide free-radical formation when incubated with either rat liver or kidney microsomes, but not with those of the heart or testes. Pretreatment with phenobarbital potentiated this effect in liver microsomes, while incubation with metyrapone decreased in renal microsomes. Both (+)- and (-)-gossypol exhibited similar potencies in renal or hepatic microsomes in vitro. At 100 mg/kg, both (+)- and (-)-gossypol were able to cause increases in SGPT in rats 12 and 24 h following the administration. The equipotency between the two isomers in causing toxic effects to some of the somatic tissues and the stereo-selectivity of (-)-gossypol to induce antispermatogenic effects indicate that gossypol may actually exhibit two categories of cytotoxic effects to different organs and tissues. This suggests that one may be able to eliminate one effect while keeping the other.     

Studies on the synthesis of sesquiterpene lactones, 14. Syntheses of (-)-arbusclin D and (+)-4-EPI-arbusclin D: the stereochemical assignment of arbusclin D.

Efficient syntheses of (-)-arbusclin D and (+)-4-epi-arbusclin D are reported. By these syntheses the C-4 stereochemistry of arbusclin D and the absolute configuration of (-)-arbusclin D have been determined to be a s shown in structure 1. The biological activities, such as cytotoxic activity toward P-388 lymphocytic leukemia, plant growth regulating activity, and antimicrobial activity of compounds 1, 3, 7, 9, 12, and 14 were also studied.     

Efficient formal total synthesis of physostigmine and physovenine: conformational analysis of key intermediates

An efficient route for the formal total synthesis of physostigmine (1) and physovenine (2), alkaloids from 5-methoxyindole-3-acetonitrile, through a Grignard reagent 1,4-addition, is described. 2-Hydroxyindolenine 5, the key advanced intermediate for the synthetic targets, was converted either to esermethole (12) via a high-yielding (28%) seven-step sequence or to the C-ring oxygenated analogue 15 in a five-step sequence and 23% overall yield. (1)H NMR and molecular modeling analyses of esermethole (12) and the furoindolines 13 and 15 were used to deconvolute weighted time-average vicinal coupling constants to provide definite solution-state conformational preferences in CD(2)Cl(2) solvent.     

Synthesis of 16,18-dihydroxycleroda-3,13Z-dien-16,15-olide, (+)-16-hydroxycleroda-3,13Z-dien-16,15-olide, and (-)-hydroxyhalima-5(10),13-dien-16,15-olide from (+)-hardwickiic acid

Syntheses of three enantiomers of natural hydroxybutenolide diterpenes, 16,18-dihydroxycleroda-3,13Z-dien-16,15-olide (4), (+)-16-hydroxycleroda-3,13Z-dien-16,15-olide (5), and (-)-16-hydroxyhalima-5(10),13Z-dien-16,15-olide (6), via a furan photosensitized oxygenation reaction of (+)-hardwickiic acid (2), are described.     

Facile access to optically active labdane-type diterpenes from (+)-manool. Synthesis of (+)-coronarin E, (+)-15,16-epoxy-8(17),13(16),14-labdatriene, and (+)-labda-8(17),13(Z)-diene-15,16-diol

An efficient method for the synthesis of (+)-coronarin E (1), (+)-15,16-epoxy-8(17),13(16),14-labdatriene (2), and (+)-labda-8(17),13(Z)-diene-15,16-diol (3) from (+)-manool is described.     

Synthesis of (+)-cyclozonarone and the absolute configuration of naturally occurring (-)-cyclozonarone

Synthesis of (+)-cyclozonarone (1) has been achieved using (-)-polygodial (3) as chiral starting material. The absolute configuration of naturally occurring (-)-cyclozonarone was established as 5R,10R by comparison of spectral data and optical rotation with those of (+)-cyclozonarone.     

调和饮对绝经前乳腺癌PR（＋）ER（＋）HER-2（-）子宫内膜的影响

目的：探讨中药自拟方调和饮对绝经前经手术放化疗后口服内分泌药物三苯氧胺的乳腺癌患者子宫内膜的影响,为临床提供资料。方法：选取2011年1月～2011年12月期间,黑龙江中医药大学附属二院肿瘤科符合纳入及排除标准的乳腺癌患者60例。选取住院天数、中医临床症状、辅助检查结果等相对完整的患者随机分为对照组（只口服他莫昔芬）,治疗组（口服他莫昔芬同时口服调和饮）各30例,并就收集的资料进行统计分析。结果：①治疗组治疗前子宫内膜厚度为（4.13±1.55）,治疗后子宫内膜为（5.83±2.32）,与治疗前相比有显著性差异（P〈0.01）。②治疗后两组子宫内膜的比较治疗组为（5.83±2.32）,对照组为（8.70±2.87）,经统计学分析有显著性差异（P〈0.01）。结论：调和饮对于绝经前手术放化疗后乳腺癌口服他莫昔芬所致子宫内膜的变化经统计学分析有明显改善作用。     

Stereoselective total synthesis of (3R,8S)-falcarindiol, a common polyacetylenic compound from umbellifers

The first stereoselective total synthesis of (3R,8S)-falcarindiol (1) from L-tartaric acid and D-xylose is reported, via the Cadiot-Chodkiczwicz reaction, to couple 1-bromoalkyne (2) with 3(R)-(tert-butyldiphenylsilyloxy)-1-penten-4-yne (3).     

(+)- and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (red-mold rice)

The structures of two enantiomeric azetidine-type amino acids isolated from the n-butanol-soluble fraction of the 70% ethanol extract of red-mold rice fermented with Monascus pilosus were established to be (+)- [1; (+)-monascumic acid] and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids [2; (-)-monascumic acid] based on spectroscopic methods.     

Biogenetic-type synthesis of (+)-cymbodiacetal, a constituent of Cymbopogon martinii

A biogenetic-type synthesis of (+)-cymbodiacetal (1), a novel bismonoterpenoid dihemiacetal, is described.     

Expedient synthesis of (S)- and (R)-norcoclaurine from (S)- and (R)-norarmepavine [corrected] prepared by the 1-phenylethylurea method

(+/-)-Norarmepavine [3] [corrected] prepared by Bischler-Napieralski synthesis afforded, on reaction with (S)-(-)-1-phenylethylisocyanate, ureas 4 and 5 which were separated and purified by crystallization from EtOH and 70% HOAc. Alcoholysis of 4 and 5 with sodium butoxide in n-BuOH afforded (S)-norarmepavine [3a] and (R)-norarmepavine [3b] [corrected], respectively. Hplc analysis of ureas prepared from 3a and 3b with (S)-(-)-1-phenylethylisocyanate showed them to be optically pure alkaloids. Refluxing 3a and 3b with 48% HBr afforded the hydrobromide salts of (S)-norcoclaurine [1a] and its (R)-isomer 1b, respectively.     

(-)-儿茶素没食子酸酯和(+)-表儿茶素对心肌细胞保护作用研究

目的:观察(-)-儿茶素没食子酸酯[(-)-CG]和( )-表儿茶素[( )-EC]对心肌细胞黄嘌呤/黄嘌呤氧化酶体系损伤的保护作用.方法:建立心肌细胞黄嘌呤/黄嘌呤氧化酶体系损伤模型,倒置显微镜观察加入(-)-CG、( )-EC后细胞形态学变化;噻唑盐比色法测定细胞活性;测定细胞培养液中乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量.结果:(-)-CG、( )-EC能够增加心肌细胞存活率,降低心肌细胞LDH的漏出量,增加SOD活性,降低培养液中MDA的含量.结论:(-)-CG、( )-EC具有抗体外培养大鼠乳鼠心肌细胞黄嘌呤/黄嘌呤氧化酶体系损伤的作用.     

Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1, 2-dihydroxy- 1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3' ',4' ',5' '-trimethoxyphenyl)-ethane

The synthetic (E)-isomer (3b) of natural combretastatin A-1 (1a) isolated from the African bushwillow Combretum caffrum was the focus of chiral hydroxylation (Sharpless) reactions as part of a structure-activity relationship study. The resulting (R,R)- and (S,S, )-diols (6 and 7) and synthetic intermediates were evaluated against a series of cancer cell lines, microorganisms, and tubulin. Chiral diols 6 and 7 showed increased activity against the P-388 murine lymphocytic leukemia cell line with ED(50) values of 3.9 and 2.9 microg/mL, respectively, when compared to the precursor (E)-stilbene 3b. In contrast, (E)-stilbene 3b exhibited more potent antibiotic activity than the chiral diols (6 and 7). Both diols, (R,R)-6 and (S, S)-7, displayed less cancer cell growth inhibition and less antibiotic activity than did natural combretastatin A-1 (1a) (P-388 ED(50) 0.25 microg/mL).     

Efficient synthesis of octandrenolone and related dipyranoacetophenones

Octandrenolone (1) was prepared in high yield by condensation of 2', 4',6'-trihydroxyacetophenone with 3-chloro-3-methylbut-1-yne in the presence of a catalytic amount of copper(I) iodide. Methylation of 1 afforded O-methyloctandrenolone (2). Oxidation of 2 with m-chloroperoxybenzoic acid followed by hydrolysis gave the racemic trans-(+)-1-(9,10-dihydro-9,10-dihydroxy-5-methoxy-2,2,8, 8-tetramethyl-2H,8H-benzo[1,2-b:3,4-b']dipyran-6-yl)ethanone (3), which confirmed the structure of the natural product previously isolated from Melicope erromangensis.