缬氨酸杀虫菊酯的合成

缬氨酸杀虫菊酯是一类很有发展前景的杀虫杀螨剂,它的菊酸部分为Ｒ－构型,菊醇部分为Ｓ－构型,其合成是由相应的缬氨酸或者它的活性衍生物与相应的醇经酯化而制得。具体过程是Ｄ－缬氨酸经６ＮＨＢｒ／ＮａＮＯ２溴化制成（Ｒ）－α－溴代异戊酸,再与对三氟甲基苯胺反应合成（Ｒ）－Ｎ－［（４－三氟甲基）苯基］α－缬氨酸,后被Ｎ－氯代琥珀酰亚胺氯化制成（Ｒ）－Ｎ－［２－氯－４－（三氟甲基）苯基］α－缬氨酸,最后与（Ｓ）－α－氰基－３－苯氧苯基甲醇用ＤＣＣ脱水酯化合成缬氨酸杀虫菊酯Ｉ（Ｒ１＝Ｆ３Ｃ,Ｒ２＝Ｈ,ＣＬ,Ｒ３＝Ｈ）。还给出了两种菊酯２×４种异构体杀虫（烟草夜蛾和家蝇）活性数据。     

两种新型菊酯杀虫效果报告

本文报道了新合成的两种菊醋杀虫活性。经对3种卫生害虫试验,结果表明：氟炔菊酯（PY902）对淡色库蚊幼虫LC50为6．8×10－3ppm;氟烯氰菊酯（PY903）为6．7×10－3ppm;按5mg／m3喷雾,前者对蚊蝇KT50分别是7．0min及6．9min;后者为16．0及12．6min;两者24h死亡率均为100％。两种化合物对蜚蠊亦有较好的杀灭效果。     

拟除虫菊酯的杀虫活性和温度的关系

除了戊酸醚酯对苜蓿蚜呈弱的正温度系数外,杀灭菊酯、二氯苯醚菊酯、氯氰菊酯、溴氰菊酯、氟氰菊酯及百树菊酯,都呈负温度系数。杀灭菊酯、戊酸醚酯、二氯苯醚菊酯、氯氰菊酯、溴氰菊酯和氟氰菊酯,对梨网蝽全部呈正温度系数。氯氰菊酯对粘虫呈负温度系数,杀灭菊酯、戊酸醚酯、二氯苯醚菊酯和溴氰菊酯都呈正温度系数。杀灭菊酯和溴氰菊酯对粘虫卵也呈正温度系数。杀灭菊酯对小菜蛾的杀虫活性,受温度的影响不明显,而戊酸醚酯则呈负温度系数。杀灭菊酯和戊酸醚酯对蚊幼呈正温度系数,而二氯苯醚菊酯则呈负温度系数。     

离体鼠肝细胞及P—450酶系与拟除虫菊酯类杀虫剂的的相互作用

经研究表明顺式氯氰菊酯．甲氰菊酯、氟氰菊酯、氰戊菊酯在正辛醇－水相中的分配系数分别为６．１３，５．５０，５．５５和４．０２。离体培养的大白鼠原代肝细胞上述杀虫（氟氰菊酯外）的吸收系数（ｑ值）分别为３２２．６，２８１．１，２０１．９。上述杀虫剂在离体培养的原代肝细胞中降解很快，湿育３０分钟后降解速率分别为９０．０％（顺式氯氰菊酯）、８６．２％（甲氰菊酯）、６９．５％（氰戊菊酯）。同时有明显的减少离体     

某些杀虫剂对数种寄生蜂的触杀活性

以不同类型的十三种杀虫剂对菜田三种寄生蜂(凤蝶金小峰、菜粉蝶绒茧蜂和啮小蜂)进行了室内触杀活性研究.拟除虫菊酯类杀虫剂对寄生蜂的击倒速度,通常较有机磷制剂快,但其杀虫活性较有机磷制剂小.在四种拟除虫菊酯中,杀灭菊酯和中西除虫菊酯对凤蝶金小蜂的毒性,较氯氰菊酯和二氯苯醚菊酯小.马拉硫磷对凤蝶金小蜂的击倒速度最快.乙酰甲胺磷等七种有机磷制剂对凤蝶金小蜂的活性都很大.微生物制剂浏阳霉素对凤蝶金小蜂无杀虫活性,但和乐果复配后.杀虫活性明显增加.在试验条件下,凤蝶金小蜂接触4.35×10^-4毫克/平方厘米药膜后,开始击倒的速度顺序为:马拉硫磷>氯氰菊脂二氯苯醚菊酯>中西除虫菊酯>敌百虫氧化乐果>甲胺磷>乙酰甲胺磷;活性顺序为:氧化乐果>马拉硫磷甲胺磷>敌百虫乙酰甲胺磷>氯氰菊酯二氯苯醚菊酯>中西除虫菊酯.杀灭菊酯对菜粉蝶绒茧蜂的击倒速度较三唑磷快,但活性较三唑碟小.杀灭菊酯和中西除虫菊酯对菜粉蝶绒茧蜂的重寄生蜂啮小蜂的活性较三唑磷小.接触拟除虫菊酯后,个别中寄或死亡的风蝶金小蜂和啮小蜂,有缓解现象.     

新拟除虫菊酯PY116的杀虫活性

为寻求杀灭室内害虫的新杀虫剂作者合成了一系列拟除虫菊酯化合物,经对尖音库蚊Culex pipiens pallens等昆虫的活性测定,筛选出对蚊虫具有突出杀虫活性的化合物——PY116。该化台物对库蚊、粘虫等的杀虫活性尚未见到正式报道。     

O—甲基O—苯基S—正丙基硫代磷酸酯的光学异构体杀虫活性的立体选择性

不对称硫代磷酸酯杀虫剂,O-甲基O-苯基S-正丙基硫代磷酸酯（T－751）,岸野茂雄等［1］首先报道其杀虫活性,尔后Treml等”做道其杀线虫活性。作者「“报道其对棉铃虫HellcoverPaarmigera（Hubner）,粘虫岭th。mnaseparata（Walker）的快速击倒活性。T－751具有不对称磷原子,存在着光学异构体,其旋光异构体的杀虫活性的立体选择性至今未见报道。最近唐除痴等“‘合成了T－751的一对光学异构体,作者以粘虫,家蝇Muscadomestlcavicina（Mao一叫。r）,尖音库蚊淡色亚种CJex……els户Jens（C。q山1卜I）为试材研究了其杀虫活性的…     

有机磷对抗拟除虫菊酯家蝇的毒力

测定敏感、抗溴氰菊酯(Del-R)、抗氯菊酯(2Cl-R)的家蝇品系对有机磷杀虫剂敌敌畏、辛硫磷及马拉硫磷的LD₅₀,α-乙酸萘酯（α-NA）酯酶动力学,酯酶的活性和酯酶的抑制作用。Del-R和2Cl-R的家蝇品系对三种有机磷杀虫剂的抗性倍数为0.966～7.190倍,均为低抗水平。三个家蝇品系的羧酸酯酶活性水平与抑制中浓度存在正相关性,说明羧酸酯酶在抗拟除虫菊酯家蝇对有机磷杀虫剂的抗性中起一定的作用。     

八氯二丙醚对氯氰菊酯的增效试验

氯氰菊酯与澳氰菊酪同属环丙烷坡酸酯取代乙烯基类化合物，由4对光学异构体组成，内有高效体顺式和反式及无效体，经催化分离即可分离顺式或反式氯氟菊酯，亦可将其无效体异构化为有效体［‘l。为了进一步提高活性，加以增效刑八氯二丙醚（以下简称SZ），具有增效作用。正试验材料10％高效体反式氯氰菊酯（南开大学有机化学元素所合成产品）；5％高效体倾反式氯氟菊酯（天津市农药总厂产品）；5％澳氰菊酯（法国罗素·代克福公司产品）；增效剂：coo，os。（扬州农药总厂产品）。试虫为德国小镜B切你对bger。nlcaL．（天津市医科大学寄生…     

家蝇对二氯苯醚菊酯的抗性及增效磷的增效作用Ⅰ:水解代谢

水解代谢在家蝇对二氯苯醚菊酯抗性中起重要作用。正常家蝇和抗性家蝇酯酶在对SV₁、SV₂等抑制剂的敏感性和电泳性质上存在着差异。抗性家蝇酯酶水解二氯苯醚菊酯的活性较高,水解乙酸-α-萘酯的活性相对比正常家蝇要低。SV₁及其在体内的代谢产物SV₂在离体和活体情况下对家蝇酯酶都有明显的抑制作用。SV₁和SV₂抑制相同的酯酶电泳条带,但SV₁的抑制作用相对小一些。SV_t对酯酶的抑制是它在家蝇体内对二氯苯醚菊酯增效的机理之一。     

cis-Nitromethylene neonicotinoids as new nicotinic family: synthesis, structural diversity, and insecticidal evaluation of hexahydroimidazo[1,2-alpha]pyridine

A series of neonicotinoids analogues of hexahydroimidazo[1,2-alpha]pyridine were modified at 5-, 6-, and 7-positions, and their insecticidal activities were evaluated. Introducing a methyl or ethyl at 7-position increased the insecticidal activities, while other substituents decreased activities. When alkyl substituents were introduced to 7-position, the insecticidal activities against Pea aphids decreased in the order methyl (7a)>ethyl (7b)>n-butyl (7e)>phenyl (7f)>n-propyl (7c)>iso-propyl (7d), p-NO(2)-phenyl (7g). Modifications at 5-, 6- or both at 6- and 7-positions with methyl or ethyl were unfavorable to activities. Interestingly, introducing methyl to 7-position not only increased insecticidal activities against pea aphids, but also show higher insecticidal activities than imidacloprid against imidacloprid-resistant brown planthopper.     

核桃楸叶乙醇提取物杀虫活性及活性成分

采用常规提取法浸提核桃楸叶的杀虫活性成分.结果表明,核桃楸叶乙醇提取物和乙醇提取物氯仿萃取相对舞毒蛾幼虫和甘蓝夜蛾幼虫具有杀虫活性.施药5 d,药液浓度≥10g.L-1时,核桃楸叶乙醇提取物和氯仿萃取相对舞毒蛾幼虫和甘蓝夜蛾幼虫的触杀作用和胃毒作用的校正死亡率均超过50%.核桃楸叶乙醇提取物对舞毒蛾幼虫和甘蓝夜蛾幼虫的触杀作用和胃毒作用强于氯仿萃取相.采用气-质联用技术GC-MS分析核桃楸叶乙醇提取物中氯仿萃取相的化学组成和相对含量.结果表明:核桃楸叶乙醇提取物中氯仿萃取相的主要杀虫活性成分为相对含量最高的胡桃醌,即5-羟基-1,4-萘醌;其他杀虫活性成分可能为对称2,2’-亚甲基6-(1,1-二甲乙基)4-甲基双酚和2-甲氧基4-乙烯基苯酚.     

Synthesis and properties of (R)-2-hydroxyglutaryl-1-CoA. (R)-2-hydroxyglutaryl-5-CoA, an erroneous product of glutaconate CoA-transferase

1) (R)-2-Hydroxyglutaryl-1-CoA was synthesised starting from (R)-5-oxotetrahydrofuran-2-carboxylic acid (gamma-lactone of (R)-2-hydroxyglutarate) which was converted to the acylchloride and condensed with N-capryloylcysteamine. The lactone ring of the resulting thiolester was opened by acid hydrolysis and the CoA derivative was obtained by transesterification. 2) Pure glutaconate CoA-transferase from Acidaminococcus fermentans catalysed the formation of the 1- and the 5-isomer of (R)-2-hydroxyglutaryl-CoA from acetyl-CoA and (R)-2-hydroxyglutarate. The isomers were separated by HPLC and characterised by their reaction with acetate under the catalysis of the CoA-transferase. V/Km for the 1-isomer was 80 times higher than that for the 5-isomer. 3) Studies with cell-free extracts from A. fermentans showed that only (R)-2-hydroxyglutaryl-1-CoA but not its 5-isomer was dehydrated to glutaconyl-1-CoA. The data indicate that (R)-2-hydroxyglutaryl-5-CoA is an erroneous product of glutaconate CoA-transferase which only occurs in vitro.     

Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsae

The occurrence of two alkaloids, 16,17-didehydro-16(E)-stemofoline and its isomer at C-4, 16,17-didehydro-4(E)-16(E)-stemofoline, were found together with a known insecticidal compound, stemofoline, in Stemona collinsae. The 16,17-didehydro-16(E)-stemofoline displayed higher insecticidal and antifeedant activities against the diamondback moth larvae than stemofoline.     

Antifeedant and Insecticidal Activity of Quassinoids against Diamondback Moth (Plutella xylostella)

The antifeedant and insecticidal activities of sixteen quassinoids against 3rd instar larvae of the diamondback moth (Plutella xylostella) were compared with those of known insect antifeedant chlordimeform (1), and the structure-activity relationship was discussed. The insecticidal activity of quassin (2) was higher than that of 1, although its antifeedant activity was nearly the same as that of the reference compound.     

Steric aspects of agonism and antagonism at beta-adrenoceptors: synthesis of and pharmacological experiments with the enantiomers of formoterol and their diastereomers.

The enantiomers of formoterol (R;R and S;S) and their diastereomers (R;S and S;R) were synthesized and purified using a new procedure which required the preparation of the (R;R)- and (S;S)-forms of N-(1-phenylethyl)-N-(1-(p-methoxyphenyl)-2-propyl)-amine as important intermediates. The enantiomeric purity obtained was greater than 99.3%, usually greater than 99.7%. The four stereoisomers were examined with respect to their ability to interact in vitro with beta-adrenoceptors in tissues isolated from guinea pig. The effects measured were (1) relaxation of the tracheal smooth muscle (mostly beta 2), (2) depression of subtetanic contractions of the soleus muscle (beta 2), and (3) increase in the force of the papillary muscle of the left ventricle of the heart (beta 1). All enantiomers caused a concentration-dependent and complete relaxation of the tracheal smooth muscle which was inhibited by propranolol. The order of potency was (R;R) much greater than (R;S) = (S;R) greater than (S;S). There was a 1,000-fold difference in potency between the most and the least potent isomer. The presence of the (S;S)-isomer did not affect the activity of the (R;R)-isomer on the tracheal smooth muscle. Also on the skeletal and cardiac muscles (R;R)-formoterol was more potent than its (R;S)-isomer. The selectivity for beta 2-adrenoceptors appeared to be slightly higher for the (R;R)-isomer than for the (R;S)-isomer. The potency of the (S;R)- and (S;S)-isomers on the papillary muscle was too low to be determined accurately.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of antiandrogens on growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115) in vivo and in vitro

Binding affinities of modified steroidal anthrasteroids, 3 beta-hydroxy-3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta, 11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-8-one (1) and 3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta,11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-3,8-dione (2), the steroid oxendolone and the nonsteroid AA560, for the androgen receptor (AR) of Shionogi carcinoma 115 (SC115) and their effects on the growth of SC115 were investigated in vivo and in vitro. The inhibitory effects of these compounds on testosterone 5 alpha-reductase of SC115 tissues were also measured. The relative binding affinities of these compounds were 3.17-0.03% of that of dihydrotestosterone, and their rank order was (1) greater than AA560 greater than oxendolone much greater than (2). In the presence of 10(-9) M testosterone, anthrasteroids and AA560 inhibited the growth of SC115 cells at 10(-7) M in a serum-free medium, but oxendolone did not. In the absence of testosterone, (1), (2) and oxendolone promoted cell growth at 10(-6), 10(-7) and 10(-7) M, respectively. However, AA560 nearly completely blocked cell growth at 10(-5) M. At a 2 mg daily dose for 13 days, (1) and AA560 powerfully inhibited tumor growth in castrated DS mice treated with testosterone propionate but oxendolone had almost no effect. Anthrasteroids and oxendolone showed weak but significant agonistic activity in vivo. Anthrasteroids markedly inhibited 5 alpha-reductase activity of SC115, oxendolone weakly and AA560 not at all. The remarkable antiandrogenic activities of (1) and AA560 may partially result from their higher affinities for the AR of SC115 but other yet unknown mechanisms may also contribute to these activities.     

Resolution and adrenergic activities of the optical isomers of 4-[1-(1-naphthyl)ethyl]-1H-imidazole.

Recently we synthesized a naphthalene analog of medetomidine, 4-[1-(1-naphthyl)ethyl]-1H-imidazole hydrochloride (1), and found it to be highly potent in adrenergic systems. The separation of optical isomers of this naphthalene analog was achieved by using the isomers of tartaric acid. The optical purities of the isomers were determined by HPLC using a chiral column. Using X-ray analysis the (+)-isomer was determined to have the S absolute configuration. It has been reported that the (+)-isomer of medetomidine (2) is the most potent enantiomer on alpha 2-adrenergic receptors. There were both qualitative and quantitative differences in biological activities of the optical isomers of 1 in alpha 1- and alpha 2-adrenergic receptor systems of guinea pig ileum and human platelets. (+)-(S)-1, but not (-)-(R)-1 was a selective agonist of alpha 2-mediated responses in ileum whereas (-)-(R)-1 was more potent than (+)-(S)-1 as an inhibitor of alpha 2-mediated platelet aggregation.     

Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2

Nedd4 and Nedd4-2 are ubiquitin-protein ligases known to regulate a number of membrane proteins including receptors and ion transporters. Regulation of the epithelial Na(+) channel by Nedd4 and Nedd4-2 is mediated via interactions between the PY motifs of the epithelial sodium channel subunits and the Nedd4/Nedd4-2 WW domains. This example serves as a model for the regulation of other PY motif-containing ion channels by Nedd4 and Nedd4-2. We found that the carboxyl termini of the six voltage-gated Na(+) (Na(v)) channels contain typical PY motifs (PPXY), and a further Na(v) contains a PY motif variant (LPXY). Not only did we demonstrate by Far-Western analysis that Nedd4 and Nedd4-2 interact with the PY motif-containing Na(v) channels, but we also showed that these channels have conserved WW domain binding specificity. We further showed that the carboxyl termini fusion proteins of one central nervous system and one peripheral nervous system-derived Na(+) channel (Na(v)1.2 and Na(v)1.7, respectively) are readily ubiquitinated by Nedd4-2. In Xenopus oocytes, Nedd4-2 strongly inhibited the activities of all three Na(v)s (Na(v)1.2, Na(v)1.7, and Na(v)1.8) tested. Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na(v) channels in vivo.     

Synthesis and stereostructure-activity relationship of three asymmetric center pyrethroids: 2-methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether and cyanohydrin ester

2-Methyl-3-phenylcyclopropylmethyl 3-phenoxybenzyl ether 2 and cyanohydrin ester 3, a couple of pyrethroids with three asymmetric centers, were synthesized. Of each of the four diastereomers of 2 and 3, only the (1R*,2R*,3R*)-2a and 3a showed significant insecticidal activities. Dual sets of enantiomers [(1R,2R,3R)-(-)-2a and (1S,2S,3S)-(+)-2a] and [(1R,2R,3R)-(-)-3a and (1S,2S,3S)-(+)-3a] were synthesized through the asymmetric cyclopropanation using the Aratani catalyst. Significant separations of insecticidal activities were observed between both the enantiomers against the tobacco cutworm (Spodoptera litura) and the common mosquito (Culex pipiens pallens); (1S,2S,3S)-(+)-2a and (+)-3a showed higher activities than their antipodes (1R,2R,3R)(-)-2a and (-)-3a. This result is the second example of such synthetic pyrethroids with three asymmetric centers.