(R)-1-(4-苄氧基-3-硝基苯基)-2-溴乙醇的合成

4-羟基-3-硝基苯乙酮经O-苄基化、溴化、还原制得1-(4-苄氧基-3-硝基苯基)-2-溴乙醇,然后酶促拆分得(R,R)-型福莫特罗的关键中间体(R)-1-(4-苄氧基-3-硝基苯基)-2-溴乙醇,总收率约25%.     

(2S,3S,5S)-2,5-二氨基-3-羟基-1,6-二苯基己烷的合成

L-苯丙氨酸用氯苄进行MO-苄基化、氰化、格氏反应、还原制得（2S，3S，5S）-5-氨基-2-二苄胺基-1，6-二苯基-3-己醇，再经钯炭催化脱苄制得抗病毒药洛匹那韦中间体（2S，3S，5S）-2,5-二氨基-3-羟基-1，6-二苯基己烷，总收率约为63％。     

2-（6-氯胡椒基）-3-[4-（2,6-二氯苄氧基）苯基]丙酸的合成

对羟基苯甲醛和2,6-二氯苄氯经O-烃化、Knoevenagel缩合、还原、C-烃化、水解脱羧反应得到具抗菌活性的2-(6-氯胡椒基)3-[4-(2,6-二氯苄氧基)苯基]丙酸.其中O-烃化在K2CO3作用下室温反应;Knoevenagel反应以三乙胺为催化剂、乙醇为溶剂,方便地获得中间体(Z)-3-[4-(2,6-二氯苄氧基)苯基]-2-氰基丙烯酸乙酯;还原反应中的原料和NaBH4为1:1摩尔量投料;总收率约65%(以对羟基苯甲醛计).     

地尔硫(艹卓)手性中间体的不对称二羟化合成法

以1，4-双（9-O-奎宁烬）-2，3-二氮杂条为手性配体，经锇催化的不对称二经化反应将反式-对甲氧基肉桂酸乙酯转化为（2R，3S-2，3-二羟基-3-（4-甲氧基苯基）内酸乙酯（2），收率87％，ee值大于99％；2与氯化业砜反应得到地尔硫[艹卓]的手性中间体（4S，5R）-4-（4-甲氧基苯基）-5-乙氧羰基-1，3-二氧杂-2-氧代硫杂环戊烷，收率85％。     

(2R,3S)-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]-3-(4-氟苯基)吗啉盐酸盐的合成

对甲氧基苯甲醛(3)和2-氨基乙醇进行还原胺化反应得2-(4-甲氧基苄胺基)乙醇(4),4和乙醛酸经成环反应得2-羟基-4-对甲氧基苄基吗啉-3-酮(5),5和三氟乙酐反应得6后与(R)-1-[3,5-二(三氟甲基)苯基]乙醇(7)缩合,再经结晶诱导不对称转化、格氏反应、氢化脱保护及成盐反应制得阿瑞吡坦关键中间体(2R,3S)-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]-3-(4-氟苯基)吗啉盐酸盐,总收率约18%(以3计)。     

(R,S)-N-(1-乙氧羰基)-3-苯丙基-L-丙氨酸的合成

(S)-苹果酸经羟基保护并脱水得(S)-2-乙酰氧基丁二酸酐,经傅-克酰化反应、钯炭催化还原后成乙酯得(S)-2-羟基-4-苯丁酸乙酯,与三氟甲磺酸酐成酯后,与L-丙氨酸苄酯发生取代反应,最后氢化脱苄制得(R,S)-N-(1-乙氧羰基)-3-苯丙基-L-丙氨酸,总收率约30％.     

1-[3-(3-苄基-4-乙氧基苄基)-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖的合成工艺研究

目的 设计并合成1-[3-（3-苄基-4-乙氧基苄基）-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖。方法 以5-溴-2-氯-4'-乙氧基二苯甲烷为原料,通过Friedel-Crafts酰基化、还原、亲核加成、还原乙酰化、脱乙酰化反应的得到目标化合物。结果 根据理化性质和波谱数据鉴定了目标化合物的结构,总收率为32%,质量分数为98.48%。结论 1-[3-（3-苄基-4-乙氧基苄基）-4-氯苯基]-1,6-二脱氧-β-D-吡喃葡萄糖的合成为tianagliflozin中杂质的研究提供了方便。     

(±)-瑞枯灵的合成

4-羟基-3-甲氧基苯乙胺和3-羟基-4-甲氧基苯乙酸经缩合、O-苄基保护得到2-(3-苄氧基-4-甲氧基苯基)-N-[2-(4-苄氧基-3-甲氧基苯基)乙基]乙酰胺,在POCl3作用下进行Bischler-Napieralski环合反应后,不经分离纯化直接与氯甲酸甲酯进行N-酰化得到7-苄氧基-1-(3-苄氧基-4-甲氧基苯亚甲基)-6-甲氧基-3,4-二氢-1H-异喹啉-2-羧酸甲酯,再经Pd-C氢化脱苄基和用四氢铝锂还原得到(±)-瑞枯灵,总收率23%.     

前列腺癌显像剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯的合成

目的制备前列腺癌显像剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯的前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐;用前体和放射性核素~(18)F合成~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯。方法以2-羟基-1-乙氧基-3-醛基苯为起始原料,经烯化、环化、磺化、成盐反应得到标记前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐;然后与放射性核素~(18)F经亲核氟代反应,得到~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯。标记前体8-乙氧基-2-(4-N,N,N-三甲基氨基苯基)-3-硝基-2H-色烯季胺三氟甲磺酸盐及各步反应中间体的结构均经核磁共振谱和质谱确证。结果与结论成功合成前列腺癌诊断显影剂~(18)F-8-乙氧基-2-(4-氟苯基)-3-硝基-2H-色烯,标记率为(25.8±2.6)%(n=5,未经衰减校正),TLC测定其放化纯度(RCP)为97.5%,为进一步临床研究奠定了基础。     

(S)-1-叔丁氧羰基-3-羟基哌啶的合成

3-羟基吡啶经5％铑炭催化加氢还原得消旋3-羟基哌啶(3),3经D-酒石酸衍生物(2S,3S)-N-(4-氯苯基)-2,3-二羟基丁酰胺酸(4)拆分,再在三乙胺作用下与二碳酸二叔丁酯“一锅法”反应制得(S)-1-叔丁氧羰基-3-羟基哌啶,总收率约40％.     

(R)-(-)-1-(2-萘基)-2-N-甲基氨基乙醇的合成

目的研究拟β-肾上腺素(R)-(-)-1-(2-萘基)-2-N-甲基氨基乙醇(1)的合成方法.方法以β-萘乙烯(2)为原料,通过烯烃的Sharpless不对称双羟化、环化、选择性开环、催化氢化、甲酰化、还原等6步反应制备目标产物.结果与结论设计的合成路线以β-萘乙烯计,6步反应总收率为39.3%,ee值高达97%～99%,合成路线易行.目标产物的结构经质谱、红外光谱、1H-NMR和13C-NMR确证.     

(S)-(-)-氨磺必利-D-(-)-酒石酸盐的合成

目的研究（S）-（-）-氨磺必利-D-（-）-酒石酸盐的制备方法。方法以4-氨基-2-甲氧基-5-巯基苯甲酸为原料,经乙基化、氧化得4-氨基-2-甲氧基-5-乙基磺酰基苯甲酸（4）,另由1-乙基-2-氨甲基吡咯烷经D-（-）-酒石酸拆分得S-（-）-1-乙基-2-氨甲基吡咯烷（6）,4与6缩合制得S-（-）-氨磺必利（7）,再与D-（-）-酒石酸成盐制得目标物S-（-）-氨磺必利-D-（-）-酒石酸盐（1）。总收率达25%（以4-氨基-2-甲氧基-5-巯基苯甲酸计算）。结果所得产物经元素分析,红外光谱、核磁共振谱及质谱确证了结构。结论本方法原料易得,反应条件温和,产品质量易控制。     

3-(R)-(碱基)-4-(S)-羟基-5-(R)-羟亚甲基四氢呋喃的合成及抗肿瘤活性

目的：研究一系列３（Ｒ）单脱氧异核苷的合成和抗肿瘤活性。方法和结果：由Ｌ木糖出发,合成了环氧化物５（Ｒ）二甲氧甲基３（Ｓ）,４（Ｓ）环氧四氢呋喃４;在碱性条件下,利用嘌呤的Ｎ９位或嘧啶的Ｎ１位对环氧化物进行亲核进攻,得到一系列３（Ｒ）单脱氧异核苷５ａｄ和６ａｄ;并进行了体外抗肿瘤活性筛选。结论：其中３（Ｒ）单脱氧异核苷５ａｄ为首次报道;同已报道的３（Ｓ）单脱氧异核苷合成方法相比,路线缩短,收率提高。在体外抗肿瘤和端粒酶抑制活性筛选中,只有化合物６ａ显示了对ＢＩＵ细胞较弱的抑制活性,其余均未显示有意义的抗肿瘤活性和端粒酶抑制活性。     

Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain

(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.     

2-(2-(3-(2-(7-氯-2-喹啉基)乙烯基)苯基)-3-氧代丙基)苯基丙醇的合成工艺

目的对2-(2-(3-(2-(7-氯-2-喹啉基)乙烯基)苯基-3-氧代丙基)苯基)丙醇的合成工艺进行研究。方法以间氰基苯甲醛和邻甲基苯乙酮分别作为起始原料,经过缩合、格氏反应、羟基保护、羟甲基反应、卤化反应,缩合得到最终目标产物。结果总收率为质量分数47.5%。结论该工艺原料易得,降低了制备成本、简化了反应操作条件、提高了产率,更适合工业化生产。     

左旋泮托拉唑钠的合成

5-二氟甲氧基-2-[[(3,4-二甲氧基-2-吡啶基)甲基]硫基]-1H-苯并咪唑在由D-(-)-酒石酸二乙酯-四异丙醇钛-水(2∶1∶0.5)制成的手性络合物和N,N-二异丙基乙胺(DIPEA)作用下,经过氧化羟基异丙苯不对称氧化,再用乙腈重结晶制得左旋泮托拉唑,在乙酸乙酯中经氢氧化钠溶液成盐后冷却析晶,即可制得高纯度左旋泮托拉唑钠,总收率约70%,纯度99.9%。     

Synthesis and antimicrobial activity of some 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-4-bromo-2-pyrazolines and 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-2-pyrazolin-4-ones

A series of 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-2-pyrazolin-4-ones (4a-e) have been synthesized by the oxidation of 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-4-bromo-2-pyrazolines (3a-e) with dimethylsulfoxide. The structure has been established on the basis of spectral data (IR,1H NMR). The synthesized compounds have been screened in vitro for their possible antimicrobial activity.     

Synthesis and antirhinovirus activity of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)-9H-purines

A series of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)purines was synthesized and tested for antirhinovirus activity. Most of the compounds were synthesized by alkylation of 6-chloro-2-(trifluoromethyl)-9H-purine with the appropriate benzyl halide followed by displacement of the chloro group with dimethylamine. Alternatively, 6-(dimethylamino)-2-(trifluoromethyl)purine was alkylated with the appropriate benzyl halide. Although several different aryl substituents provided compounds with IC50's = 0.03 microM against rhinovirus serotype 1B, no congener was significantly more active than the parent 2. Twenty-three compounds were tested against 18 other serotypes, but none exhibited a uniform profile of activity.     

8-chloro-(S)- and -(R)-10-((S)-and -(R)-3'-methylethylaminopyrrolidino)- 10,11-dihydrodibenzo(b,f)thiepins. Synthesis and pharmacological studies.

The synthesis for 8-chloro-(S)- and -(R)-10-[(S)- and -(R)-3'-methylethylaminopyrrolidino]-10,11-dihydrodibenzo[b,f]thiepins is presented. The absolute configuration at position 3' of the aminopyrrolidino side chain is known from synthesis and corresponds to the asymmetric carbon atom in (S)- or (R)-aspartic acid. The absolute configuration at C-10 of the dihydrodibenzo[b,f]thiepin ring system was deduced from ORD-CD analysis coupled with degradation of partially resolved (+)-8-chloro-10-amino-10,11-dihydrodibenzo[b,f]thiepin to (+)-(S)-1,2-diphenylethylamine. The four isomers were studied in mice for their ability to block conditioned avoidance responding, antagonize oxotremorine, and act as analgetics and anticonvulsants. These compounds were found to be nonselective antagonists of histamine, acetylcholine, and BaCl2 in vitro. The compounds exerted effects similar to those of chlorpromazine. Stereoselective differences in activity between diastereoisomers, rather than between enantiomorphs, were generally observed.