(9S)-12-亚甲基红霉素衍生物的合成及体外抗菌活性

目的合成新的具有抗菌活性的红霉素衍生物。方法以红霉素为原料，合成中间体2′-O,4″-O-二苯甲酰基-(9S)-9-O,11-O-异丙基-12-亚甲基红霉素与6,7-去氢-2′-O,4″-O-二苯甲酰基-(9S)-9-O,11-O-异丙基-12-亚甲基红霉素，进而合成相应(9S)-9-O,11-O-亚乙基-12-亚甲基衍生物。产物结构经¹³C NMR,FAB-MS确证。对所得化合物进行体外抗菌活性测定。结果制备11个红霉素衍生物，其中5个未见文献报道。化合物9和12进行了体外抗菌活性测定。结论化合物9和12表现出较弱的抗菌活性。     

3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的3位羟基红霉素衍生物。方法　以红霉素A为原料,经9位酮基肟化,9位肟羟基,2′位羟基和3′位二甲胺基同时苄基化,6位羟基甲基化,水解去3位克拉定糖,氢化还原脱苄基,对甲基苄基或邻氯苄基取代9位肟羟基等6步反应,制得3-羟基-6-O-甲基红霉素-9-肟基衍生物,其结构经¹³CNMR ,FAB MS确证。结果　共制得7个化合物,对其中4个(5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　5 ,7,8对部分红霉素诱导耐药菌有一定的活性     

构树叶的化学成分

为研究构树叶(Broussonetia papyrifera)的化学成分，用Diaion HP-20，Toyopearl HW-40C，Sephadex LH-20，silica gel等柱色谱方法进行分离，根据其理化性质和波谱数据鉴定化合物结构。分离得到了19个化合物，分别鉴定为芹菜素(1)，芹菜素-7-O-β-D-吡喃葡糖苷(2)，柯伊利素-7-O-β-D-吡喃葡糖苷(3)，芹菜素-7-O-β-D-吡喃葡糖醛酸苷(4)，牡荆素-7-O-β-D-吡喃葡糖苷(5)，木犀草素(6)，5,7,4′-三羟基-6-C-［a-L-鼠李糖(1→2)］-β-D-葡糖黄酮碳苷(7)，5,7,4′-三羟基-8-C-［α-L-鼠李糖(1→2)］-β-D-葡糖黄酮碳苷(8)，异牡荆素(9)，牡荆素(10)，苯甲酸苯甲酯-2,6-二-O-β-D-吡喃葡糖苷(11)，(2R,3R,5R,6S,9R)-3-羟基-5,6-环氧-β-紫罗兰醇-2-O-β-D-葡糖苷(12)，(2R,3R,5R,6S,9R)-3-羟基-5,6-环氧-乙酰-β-紫罗兰醇-2-O-β-D-葡糖苷(13)，ficustriol (14)，(6S,9S)-玫瑰花苷(15)，3β-羟基-5α,6α-环氧-β-紫罗兰酮-2α-O-β-D-葡糖苷(16)，icariside B₁ (17)，sammangaoside A (18)，3-羟基-5α,6α-环氧-β-紫罗兰酮(19)。化合物11、12、13为新化合物，其余化合物为首次从该属植物中分离得到。     

拟人参皂苷F11在大鼠体内的药物代谢研究

目的探讨拟人参皂苷F11在大鼠体内的药物代谢产物及其过程.方法ip拟人参皂苷F₁₁后,应用TLC分析排泄物中的代谢产物,并利用制备薄层分离制备代谢产物,通过波谱解析(MS,¹HNMR,¹³CNMR,¹H-¹HCOSY)确定其结构.结果从粪便中分离鉴定了3种代谢产物,分别为拟人参皂苷R_T5,ocotillol和1个新的代谢产物F-3-1,并确定其结构为6-O-α-L-吡喃鼠李糖基(1-2)-β-D-吡喃葡糖基-(20S,23S,24R)-达玛-20(24)-环氧-3β,6α,12β,23,25-五醇(6-O-α-L-rhamnopyranosyl-(1-2)-β-D-glucopyranosyl-(20S,23S,24R)-dammar-20(24)-epoxy-3-β,6α,12β,23,25-pentanol).但在尿液和胆汁中并未发现任何代谢产物.结论拟人参皂苷F₁₁不被肝脏代谢,但胆汁排泄物可在肠道被代谢为水解和氧化产物.     

西洋参茎叶总皂苷碱降解成分西洋参茎叶总皂苷碱降解成分

目的研究西洋参茎叶总皂苷碱降解成分。方法采用硅胶柱色谱并结合HPLC进行分离纯化，通过波谱分析鉴定化合物的结构。结果从西洋参茎叶总皂苷碱降解产物中分离得到9种成分，分别鉴定为：20(S)-原人参二醇(I)，20(S)-达玛-25(26)-烯-3β,12β,20-三醇(II)，24(R)-ocotillol (III)，20(S)-原人参三醇(IV)，20(S)-达玛-25(26)-烯-3β,6α,12β,20-四醇(V)，达玛-20(21),24-二烯-3β,12β-二醇(VI)，达玛-20(21),24-二烯-3β,6α,12β-三醇(VII)，20(S),24(S)-达玛-25(26)-烯-3β,6α,12β,20,24-五醇(VIII)，20(S)-达玛-23-烯-25-过氧羟基-3β,6α,12β,20-四醇(IX)。结论碱降解20位S构型未改变。V，VII，VIII，IX为4个新化合物，并利用2D-NMR技术对新化合物的氢和碳的化学位移进行了归属。其中I对HCT-8人结肠癌细胞具有较强的细胞毒活性。     

栾树种子的化学成分研究

目的：分离鉴定栾树(Koelreuteria paniculata Laxm.)种子的化学成分。 方法：分别用石油醚回流提取和95% EtOH浸提, 硅胶柱色谱分离, IR,MS,UV,¹HNMR,¹³CNMR等方法确定结构。 结果：分得8个化合物,分别为3/-O-十四烷酰基-1-腈基-2-甲基-1,2-丙烯(1), 3-O-二十碳-14,15-烯酰基-1-腈基-2-甲基-1,2-丙烯(2), 3-O-二十碳-14,15-烯酰基-4-O-十八烷酰基-1-腈基-2-氧代亚甲基-1,2-丙烯(3), 3-O-(6′-亚油酰基-葡萄糖)-β-谷甾醇(4), 1-O-β-D-葡萄糖-2-O-油酸-3-O-十六烷酸甘油酯（5), 1-O-十六烷酸甘油酯（6), 14,15-二十碳烯酸（7),三油酸甘油酯（8)。 结论：1～3为新化合物, 4～8系首次从该植物中分得, 并归属其波谱信号。     

(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯单晶制备及其结构表征

目的 培养(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯单晶,并进行晶型表征和立体结构确证。方法 用醋酸乙酯-甲基叔丁基醚（1∶1）体系培养单晶,并采用热重法、差示扫描量热法、粉末X射线衍射和单晶X射线衍射分析。结果 制备得到无色块状晶体;样品熔点约为114 ℃;该晶胞属于正交晶系,空间群为P2₁2₁2₁,分子式为C₁₃H₂₂N₂O₅,相对分子质量为286.33,晶体密度为1.152 mg/mm³,绝对构型为S,S构型。结论 确定了(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯的立体构型,培养的晶体为非水合物和溶剂化物。     

中药大血藤的酚性化合物

目的对中药大血藤干燥藤茎的化学成分进行研究。方法采用现代色谱技术分离化合物，运用现代波谱技术(IR，MS，¹H NMR，¹³C NMR，²DNMR)对所得化合物的结构进行鉴定。结果从大血藤的藤茎中分得10个酚类化合物，分别鉴定为1-O-(香草酸)-6-(3″,5″-二-O-甲基-没食子酰基)-β-D-葡糖苷(I)、(-)-表儿茶素(II)、阿魏酸-对羟基苯乙醇酯(III)、3-O-咖啡酰奎宁酸(IV)、3-O-咖啡酰奎宁酸甲酯(V)、罗布麻宁(VI)、香草酸(VII)、原儿茶酸(VIII)、3,4-二羟基-苯乙醇(IX)、4-羟基-苯乙醇(X)。结论化合物I为新化合物，化合物III～VI和VIII～X为首次从该植物中分得。     

平消胶囊联合左甲状腺素钠治疗结节性甲状腺肿的临床研究

目的 对狭叶薰衣草Lavandula angustifolia中的木脂素类化合物进行研究。方法 运用RP-HPLC、TLC、硅胶、凝胶、MCI-gel树脂等方法进行分离纯化,并根据理化性质和波谱数据鉴定化合物的结构。结果 从狭叶薰衣草中分离得到11个木脂素类化合物,分别鉴定为松脂醇（1）、丁香树脂醇（2）、fraxiresinol-4''-O-β-D-glucopyranoside（3）、syringaresinol-4''-O-β-D-glucopyranoside（4）、8-hydroxypinoresinol-4-O-β-D-glucopyranoside（5）、rel-（2α,3β）-7-O-methylcedrusin（6）、落叶松脂醇-4''-O-β-D-葡萄糖苷（7）、（2S,3R）-2,3-dihydro-2-（4-hydroxy-3-methoxyphenyl）-3-hydroxymethyl-7-methoxybenzofuran-5-（trans） propen-1-ol-3-O-β-glucoside（8）、（7S,8R）-dihydrodehydrodiconiferyl alcohol-9-β-D-glucopyranoside（9）、（7R,8R）-7,8-dihydro-9''-hydroxyl-3''-methoxyl-8-hydroxymethyl-7-（4-hydroxy-3-methoxyphenyl）-1''-benzofuranpropanol-9''-O-β-D-glucopyranoside（10）、（E）-3-（（2S,3S）-2-（4-hydroxy-3-methoxyphenyl）-3-hydroxymethyl-7-methoxy-2,3-dihydrobenzofuran-5-yl） allyl-2-hydroxyacetate（11）。结论 11个化合物均首次从狭叶薰衣草中分离得到。     

制首乌中1个新的四羟基二苯乙烯苷的结构鉴定及其心血管活性研究

目的　从制首乌(Radix Polygoni multiflori Preparata)水溶性部分寻找心血管活性成分。方法　采用体外抑制血管平滑肌细胞(SMC)增殖活性跟踪筛选,利用Sephadex,反相硅胶柱色谱、HPLC对制首乌水溶性成分进行分离纯化,应用理化常数测定和光谱(UV,IR,MS,¹HNMR,¹³CNMR,2D-NMR)分析技术鉴定结构。结果　分离并鉴定了1个单体化合物2,3,5,4′-四羟基二苯乙烯-2-O-(6″-O-α-D-吡喃葡糖)-β-D-吡喃葡糖苷(I)。结论　I为新化合物,具有较强的抑制SMC增殖活性。     

Synthesis and antibacterial activities of C-21 functionalized derivatives of (9R)-9-amino-9-deoxoerythromycins A and B.

Selective protection of (9R)-9-amino-9-deoxoerythromycin A allowed for elimination of the 12-hydroxyl group to afford a versatile 12,21-olefin intermediate. Further modifications of the intermediate led to the syntheses of (9R)-9-deoxo-9-(N,N-dimethylamino)-12,21-epoxyerythromycin B, (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin A, and (9R)-9-deoxo-9-(N,N-dimethylamino)-21-hydroxyerythromycin B. All three compounds retained antibacterial activity against several organisms normally susceptible to (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A. However, the 21-hydroxylated erythromycin A analogue was weaker in potency than the corresponding erythromycin B congener and much weaker than the epoxy derivative. This suggests that while substitution of a polar functionality at C-21 does not abolish antibacterial activity, introduction of vicinal polar groups at both C-12 and C-21 may lead to reduction in potency. Nevertheless, these 21-functionalized derivatives of (9R)-erythromycylamine provide an entry into novel analogues of the important macrolide antibiotic erythromycin.     

9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A

A series of 9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A (4) have been prepared and their antibacterial activities compared to those of erythromycin A and 9-dihydroerythromycin A. Many of the cyclic acetal derivatives showed better antibacterial activity than their parent 4. In particular, the acetaldehyde acetal (9-O,11-O-ethylidene-9-dihydroerythromycin A) (8b) showed good antibacterial activity in comparison with erythromycin A but was not sufficiently improved in vivo to warrant progression.     

3-Keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis and in vitro activity

A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A were prepared with a novel synthetic route, which include 6 reaction steps--oximation, protection, hydrolysis, oxidation, deprotection and addition. The antibacterial activity of these compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms. Several of these derivatives showed improved antibacterial activity against some erythromycin-resistant organisms as compared to erythromycin A.     

Synthesis and antibacterial activities of novel 12-O-methylerythromycin A derivatives

The novel erythromycin A derivatives: 9(S)-9-dihydro-12-O-methylerythromycin A (6) and 12-O-methyerythromycin A (3), have been prepared using a new synthetic approach. The critical step is the regioselective methylation of the 12-hydroxyl of the boron complex of 2',4"-O-bis(trimethylsilyl)-9(S)-9-dihydroerythromycin A (8), which has unprotected 6-, 9- and 11-hydroxyl groups. The antibacterial activities of these new derivatives were compared with those of erythromycin A (1), clarithromycin (2) and 9(S)-9-dihydroclarithromycin (5).     

Synthesis and activity of C-21 alkylamino derivatives of (9R)-erythromycylamine.

Novel analogs of (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A bearing N-alkylamino substituents at the C-21 position were synthesized. These compounds retained antibacterial activity. The C-21, N,N-dimethylamino analog showed a modest improvement in activity against some Gram-negative bacteria.     

Genotoxicity of 12 Mycotoxins by the SOS/umu Test: Comparison of Liver and Kidney S9 Fraction

Liver S9 fraction is usually employed in mutagenicity/genotoxicity in vitro assays, but some genotoxic compounds may need another type of bioactivation. In the present work, an alternative S9 fraction from the kidneys was used for the genotoxicity assessment of 12 mycotoxins with the SOS/umu test. The results were compared with liver S9 fraction, and 2–4 independent experiments were performed with each mycotoxin. The expected results were obtained with positive controls (4-nitroquinoline-N-oxide and 2-aminoanthracene) without metabolic activation or with liver S9, but a potent dose-dependent effect with 4-nitroquinoline-N-oxide and no activity of 2-aminoanthracene with kidney S9 were noticed. Aflatoxin B1 was genotoxic with metabolic activation, the effect being greater with liver S9. Sterigmatocystin was clearly genotoxic with liver S9 but equivocal with kidney S9. Ochratoxin A, zearalenone and fumonisin B1 were negative in all conditions. Trichothecenes were negative, except for nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, T-2 and HT-2 toxins, which showed equivocal results with kidney S9 because a clear dose-response effect was not observed. Most of the mycotoxins have been assessed with kidney S9 and the SOS/umu test for the first time here. The results with the positive controls and the mycotoxins confirm that the organ used for the S9 fraction preparation has an influence on the genotoxic activity of some compounds.     

Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether

A series of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 μg ml(-1)) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.     

新3,5-二取代唑烷酮抗菌剂的合成及其体外抑菌活性新3,5-二取代唑烷酮抗菌剂的合成及其体外抑菌活性

目的设计、合成唑烷酮新化合物并测定其体外抑菌活性。方法对文献方法进行了改进，在文献报道的构效关系基础上，设计、合成唑烷酮新化合物并测定体外抑菌活性。结果合成了39个新化合物，其中目标物18个，其结构经IR,¹HNMR,MS等方法确证。16个化合物显示出较好的抑菌活性，其中化合物9，10，10b对4种试验菌的MIC50和 MIC90值小于或接近4种对照药，化合物9a和11c没有抑菌活性。结论化合物9，10和10b值得进一步研究。