从平贝母茎叶中分离的平贝啶甙的结构

本文报道自平贝母(Fritillaria ussuriensis Maxim)的地上茎叶中分得一种新的甾体生物碱甙,定名为平贝啶甙(pingbeidinoside),mp 242～243.2℃[a]_D²⁵+6.9°(c 0.145,MeOH)。经IR,MS,¹HNMR和¹³CNMR谱解析,推定其结构为3β,16α,20-三羟基-Δ⁵-22,26-缩亚胺胆甾烷-25-O-α-D-葡萄糖甙。     

粉防己碱,小檗胺等四氢异喹啉类生物碱对大鼠脑内M-胆碱受体的作用

用放射受体结合方法,研究了36种四氢异喹啉类生物碱及其半合成衍生物对大鼠脑内M-胆碱受体的结合特性。实验发现,粉防己碱对M-胆碱受体的亲和力最高,其K_i值为7.3×10^-8mol/L。小檗胺、四氢黄连碱和半合成原小檗碱衍生物B₁亦具有较高亲和力,K_i值分别为1.9×10^-7,6.8×10^-7和8.1×10^-7mol/L。四氢小檗碱半合成原小檗碱衍生物B₂,B₃,B₄,B₅,B₆和半合成小檗胺衍生物E₁及半合成蝙蝠葛碱衍生物D₁对M-胆碱受体的亲和力为中等强度,K_i值在1～2×10^-6mol/L之间。实验结果提示,某些四氢异喹啉类生物碱的药理作用可能与M-胆碱受体有关。     

某些四氢异喹啉类生物碱对大鼠脑内多巴胺和5-羟色胺受体的作用

本文报道十二种四氢异喹啉类生物碱对大鼠脑内D-2,5-HT₁和5-HT₂受体的结合特性。其中l-千金藤碱(l-STP)对这三种受体均有较高的亲和力,其Ki值分别为1.7×10^-7,9.4×10^-8和1.8×10^-7mol。l-莲碱(l-REM)对5-HT₂受体的亲和力与Z-STP相似(Ki=1.7×10^-7mol)。THB,THC和THJ对D-2受体的亲和力介于l-SPD和l-THP之间。本文报道的多数生物碱能同时影响两种或两种以上受体部位的结合特性,提示它们对单胺神经系统可能有复杂的相互作用。     

麻黃揮发油的研究

本文报告由麻黄中提取出一种淡黄色具有花香的挥发油,n_D²⁰1.4940,[α]_D²⁰—31.44°,d₂₀²⁰0.8819。将此油反复减压分馏和用氧化铝柱层离后得到一种萜醇(C₁₀H₁₈O),经制备其衍生物和红外吸收光谱、气相层离法鉴定,证明为l-a-萜松醇。     

湖北贝母化学成分的研究 Ⅲ.湖贝甲素甙的分离和鉴定

本文报道了自湖北贝母Fritillaria hupehensis Hsiao et K.C.Hsia醇提取总生物碱中分离到一种新的生物碱甙,C₈₃H₅₅NO₇,mp 241～244℃。经红外光谱、核磁共振氢谱及质谱分析,结合水解及衍生物的制备证明生物碱甙的结构为5α,14α-瑟瓦林-6α-羟基-3αβ-D-葡萄糖甙,命名为湖贝甲素甙(hupeheninoside)。     

紫乌头生物碱的化学研究

从紫乌头根中分出四种新二萜生物碱,分别命名为紫乌生、紫乌生宁、紫乌亭和紫乌定。根据红外光谱、紫外光谱、质谱、氢谱和碳谱以及制备衍生物,证明了前三个生物碱的结构(3,4,5),对紫乌定的结构曾初步推定为(8)⁽¹⁾;后来,经单晶X射线衍射结构分析修正为(9)。此外,作者认为,根据化学结构特点应从C₁₉二萜生物碱中划分出C-4失甲基的一类生物碱,称C₁₈二萜生物碱。     

四氢异喹啉类生物碱对大鼠脑内α肾上腺素受体的作用

应用放射受体结合法研究了近30种四氢异喹啉类(TIQs)生物碱对大鼠脑内α肾上腺素受体的作用。其中l-CBN,l-THC和l-STP对α₁受体亲和力最高,K_i值为～2.0×10^-7mol/L。其次是DHS,XLP和l-DCT,K_i值分别为4.7×10^-7,6.5×10^-7和7.6×10^-7mol/L。DHS对α₂受体亲和力最高(K_i=1.25×10^-6mol/L),l-REM次之。对α受体亚型亲和力选择比K_i(alpha-2)/Ki(alpha-1)最高的是l-STP(357) 和XLP(154),它们对α₂受体几无亲和力(K_i>10^-4mnl/L)。提示l-STP和XLP对α₁受体有较高的选择性。l-SPD和l-THP对α₁和α₂受体亲和力相近,均为中等强度。THJ,DRC及l-TTD等6种TIQs对α₁和α₂受体均无亲和力(K_i>10^-4mnl/L)。     

中国乌头的研究——ⅩⅩ.赣皖乌头的研究

本文报道了从赣皖乌头Aconitum finetianum Hand-Mazz的根中分到三个二萜类生物碱A.B.c。经鉴定B和C分别为lappaconitine和ranaconitine。碱A,C₃₂H₄₄N₂O₁₀,熔点220～221℃,[α]_D²²+44.7°(甲醇),为一个新生物碱,暂称赣乌碱finaconitine,经光谱推定化学结构为10-β-羟基-冉乌头碱。     

马蔺子素的单扫描示波极谱法测定

目的建立测定马蔺子素的极谱法。方法单扫描示波极谱法。结果在8.0×10^-3 mol·L^-1 Na₂B₄O₇-1.6×10^-2 mol·L^-1 KH₂PO₄ (pH 7.7)支持电解质中,马蔺子素有一灵敏的极谱还原波,其峰电位E_p=-1.23 V(vs SCE),二阶导数峰电流i_p″与马蔺子素浓度为1.5×10^-7～5.2×10^-6 mol·L^-1呈良好线性关系(γ=0.9992,N=9),检出限为6.0×10^-8 mol·L^-1。13次测量2.0×10^-6 mol·L^-1马蔺子素还原波二阶导数峰峰电流,相对标准偏差RSD为0.87%。结论该方法灵敏、简便、快速,可用于原料药及胶囊中马蔺子素含量的测定。     

基于溶解氧乙酰螺旋霉素极谱平行催化氢波的研究

目的提出一种极谱测定乙酰螺旋霉素(ASPM)的新方法。方法应用单扫描极谱法,在含溶解氧的0.1 mol·L^-1 NH₄Cl-NH₃·H₂O(pH 8.9)缓冲液中ASPM产生1个灵敏的平行催化氢波［峰电位E_p=-1.63 V(vs SCE)］。结果该平行催化氢波的二阶导数峰峰电流i″与ASPM浓度在1.74×10^-3～3.48 μg·mL^-1呈良好线性关系(r=0.997 9,n=13),检出限为5.80×10^-4 μg·mL^-1(3σ)。对0.871 μg·mL^-1 ASPM溶液进行13次平行测定,RSD为1.24%。结论本方法可用于ASPM片剂中ASPM含量的测定。     

石虎的化学成分研究

由石虎果实的酸性乙醇提取物中分得五种单纯成分。其中四种经鉴定为吳萸內酯(Evodin或Limonin)、吳萸碱、去甲基吳萸碱和羟基吳萸碱。最后一种暂命名为石虎甲素[C₁₈H₁₈O₆,熔点262℃,[a]_D³⁰-65.5°(c=0.061,氯仿)],可使溴的冰醋酸溶液褪色,紫外和红外吸收光谱表明为不饱和酮     

Multitargeted C9-substituted ester and ether derivatives of berberrubine for Alzheimer's disease: Design,synthesis, biological evaluation,metabolic stability,and pharmacokinetics

Berberrubine is a naturally occurring isoquinoline alkaloid and a bioactive metabolite of berberine. Berberine exhibits a wide range of pharmacological activities, including cholinesterase inhibition. The cholinesterase inhibitors provide symptomatic treatment for Alzheimer's disease; however, multitarget-directed ligands have the potential as disease-modifying therapeutics. Herein, we prepared a series of C9-substituted berberrubine derivatives intending to discover dual cholinesterase and beta-site amyloid-precursor protein cleaving enzyme 1 (BACE-1) inhibitors. Most synthesized derivatives possessed balanced dual inhibition (AChE and BChE) activity in the submicromolar range and a moderate inhibition against BACE-1. Two most active ester derivatives, 12a and 11d , display inhibition of AChE, BChE, and BACE-1. The 3-methoxybenzoyl ester derivative, 12a , inhibits electric eel acetylcholinesterase (EeAChE), equine serum butyrylcholinesterase (eqBChE), and human hBACE-1 with IC₅₀ values of 0.5, 4.3, and 11.9 μM, respectively and excellent BBB permeability (P_e = 8 × 10⁻⁶ cm/s). The ester derivative 12a is metabolically unstable; however, its ether analog 13 is stable in HLM and exhibits inhibition of AChE, BChE, and BACE-1 with IC₅₀ values of 0.44, 3.8, and 17.9 μM, respectively. The ether analog also inhibits self-aggregation of Aβ and crosses BBB (P_e = 7.3 × 10⁻⁶ cm/s). Administration of 13 at 5 mg/kg (iv) in Wistar rats showed excellent plasma exposure with AUC_0−∞ of 28,834 ng min/ml. In conclusion, the multitargeted berberrubine ether derivative 13 is CNS permeable and has good ADME properties.     

国产萝芙木成分的研究I.

(1)在海南島产的蘿芙木叶中,証明了生物碱aricine的存在.(2)鉴定所含的黄酮体是刺槐素(robioin).     

胡蔓藤生物碱的化学研究 Ⅱ.胡蔓藤碱丙(humantenidine)的化学结构

自马钱科(Loganiaceae)植物胡蔓藤(Gelsemium elegans Benth.)根的生物碱提取物中分离得到的一个新的氧化吲哚生物碱,命名为胡蔓藤碱丙(humantenidine),经光谱(UV,IR,¹HNMR,¹³CNMR,MS)分析和衍生物的制备,确定其化学结构为式(Ⅰ)所示     

胡蔓藤生物碱的化学研究——Ⅱ.胡蔓藤碱丙(humantendine)的化学结构

前文我们报告了自马钱科(Loganiaceae)植物胡蔓藤(Gelsmium elegans Banth.)根的生物碱提取物,分离得到了七个生物碱,其中一个新的氧化吲哚生物碱命名为胡蔓藤碱丙(humantendine),该化合物为无色透明的胶状物,[α]_D~(18)—123°(c 0.107乙醇),其氢溴酸盐为羌色方块状结晶,mp 158～162℃。根据元素分析和质谱给出的分子量(M~+342)确定其分     

氯霉素之合成研究(二) 乙苯之硝化反应

使用硫酸脫水值为2.66的混酸进行乙苯的一硝基化。自硝化产物中分离出佔0.4%重量的檸檬黄色結晶,系一种未經报导过的二硝基乙苯酚.自稀乙醇重結晶后,熔点35～38°,元素分析与C₈H₈N₂O₅相符。此化合物在270°迅速分解,其鈉鹽和鉛鹽則分別在240°和210°猛烈分解。作为安全措施,建議在蒸餾之前用稀氫氫化鈉溶液洗滌硝化产物。分餾所得隣、对一位硝基乙苯約相等。精制品的物理常数:鄰位体,n_D¹⁹1.5373;紫外光吸收峯256mu,E_{1cm^1%336;对位体,nD¹⁹1.5458;紫外光吸收峯272mu,E1cm^1%555.文献上隣位体折光率的記載可能有誤。}     

Combined effects of metal contamination and temperature on the potworm Enchytraeus doerjesi (Oligochaeta)

Cadmium (Cd) and zinc (Zn) toxicity in Enchytraeus doerjesi after 28‐day exposure experiments was studied at 15, 20, and 25 °C. Cd lethal concentration (LC)₅₀ decreased with increasing temperature (293.01 mg kg^–1 at 15 °C, 261.62 mg kg^–1 at 20 °C, 231.79 mg kg^–1 at 25 °C). In contrast, Zn LC₅₀ increased with increasing temperature (420.21 mg kg^–1 at 15 °C and 518.42 mg kg^–1 at 20 °C). At 25 °C, a Zn LC₅₀ could not be computed owing to the lack of sufficient adult mortality (LC₅₀ > 640 mg kg^–1). The reproductive output at 20 and 25 °C was similar for each metal. Cd EC₅₀ for reproduction increased between 15 and 20 °C (from 23.93 to 35.11 mg kg^–1) and decreased between 20 °C and 25 °C (to 16.84 mg/kg). Zn EC₅₀ increased dramatically from 15 °C (41.47 mg kg^–1) to 20 °C (111.75 mg kg^–1), and then slightly from 20 °C to 25 °C (112.17 mg kg^–1). This indicated that metal–temperature effects on E. doerjesi may vary depending on the endpoint. The deleterious effects of Cd on the survival of E. doerjesi increased steadily with increasing temperature. With regard to reproduction, Cd toxicity could be exacerbated by extreme temperatures (15 and 25 °C) although conflicting pressures between high temperature and Cd toxicity may have prevented higher reproduction beyond 20 °C. The effects of Zn toxicity on survival decreased consistently with increasing temperature. The marginal increase in Zn EC₅₀ between 20 and 25 °C may explain the lack of a significant change in reproduction between the two temperatures. Energy redistribution between the below organism and higher organization endpoints in response to metal contamination may further explain these results. Copyright © 2012 John Wiley & Sons, Ltd.     

Structure and conformation of linear peptides XII. Structure of tryptophanyl-glycyl-glycine dihydrate

The crystal structure of a tripeptide, tryptophanyl-glycyl-glycine dihydrate (C₁₅H₁₈N₄O₄·2H₂O, molecular weight = 354) has been determined. The crystals are orthorhombic, space group P2₁2₁2₁ with a= 7.875 (1) A,b= 9.009(1), c= 24.307(1) and Z = 4. The final R-index is 0.058 for 1488 reflections ((sin θ/λ≤ 0.6 A^?1) with I < 2σ(I). The molecule exists as a zwitterion, with terminal NH⁺₃ and COO^? groups. The peptide units are trans and nearly perpendicular to the plane of the carboxyl group. The backbone torsion angles are: ψ₁= 132.7°, ω₁= 174.2°, φ₂ 88.2°, ψ= 8.6°, ω₂ - 179.8°, φ= - 85.2°, ψ₃₁, = - 178.1°, ψ₃₂ 5.0°. For the sidechain of tryptophan, χ₁= - 171.6°, χ₂ 101.0°.     

石蒜科生物碱的研究 Ⅲ.紫花石蒜和其他两种石蒜中的生物碱及新生物碱紫花石蒜碱

从紫花石蒜Lycoris squamigera Maxim.中分得19种结晶性生物碱,其中12种生物碱分别证明为lycorine,pseudolycorine,lycorenine,homolycorine,tazettine,norpluviine,galanthamine,epigalanthamine,vittatine,pluviine,lycoramine,hippeastrine;分得一种新生物碱,命名为紫花石蒜碱squamigerine. 紫花石蒜碱,C₁₈H₂₁O₅N,熔点260℃,[α]_D³⁴+165°(氯仿),含有次甲二氧基、氯甲基、甲氧基、羟基和双键各1个。紫花石蒜碱的分子式及官能团均与tazettine相同;熔点,[α]D及R_f值不同。因而推想紫花石蒜碱可能为tazettine的异构体。我们进行了两者的紫外及红外吸收光就业谱的比较,发现它们彼此非常相似。因为紫花石蒜碱又与epitazettine 显然不同,所以推定它可能为B/D或C/D环系统结合不同于tazettine 的立体异构体。从红花石蒜L.radiata Herb.中分得7种已知生物碱:lycorine,homolycorine,tazettine,galanthamine,lycoramine,Iycorenine和pseudolycorine.从1种栽培的黄花石蒜中也分得上述7种生物碱。     

宾川乌头中的生物碱及其结构的研究

从云南药用草乌之一的宾川乌头(Aconitum duclouxii Levl)根中分得两种结晶性生物碱,称为碱A及碱B。经鉴定,碱B为乌头碱(aconitine)。碱A分子式为C₃₄H₄₇O₁₀N,熔点168～169℃,[α]_D^28.1+28.3(C,1.43,氯仿),此系一新生物碱,命名为宾乌碱(duclouxine),经光谱分析,初步推定其化学结构式为12-β-羟基查斯乌头碱(12-β-hydroxy chasmaconitine)。宾乌碱经初步药理试验说明有镇痛作用。