新型手性N,N′-双支套索冠醚的合成及其应用

(S)-苯丙氨醇和原氯乙酸三乙酯作用得到的手性酰胺醇和手性噁唑啉分别与1,7-二氮-12-冠-4反应, 得到了两种手性N,N′-双支套索冠醚N,N′-二[(S)-N-(1-羟甲基-2-苯基乙基)乙酰胺-2]-1,7-二氮-12-冠-4 (1a)和N,N′-二[(S)-4-苄基-噁唑啉-2-亚甲基]-1,7-二氮-12-冠-4 (1b). 前者应用于D/L-肉碱的手性分离; 后者的铜配合物用于重氮醋酸酯对烯烃的不对称环丙烷化反应.     

[1-芳基甲羰基-2-(1,2,4-三唑-1-基)]乙基-N,N-二烷基二硫代氨基甲酸酯衍生物的合成、结构表征及生物活性研究

以芳香基三唑类杀菌剂三唑酮为先导物设计并合成了5个含N,N-二烷基二硫代氨基甲酸酯的芳香三唑类化合物, 通过元素分析、红外光谱、核磁共振氢谱和质谱对其结构进行了表征. 用X射线单晶衍射测定了[α-(4-甲氧基苯甲酰基)-2-(1,2,4-三唑-1-基)]乙基-N,N-二甲基二硫代氨基甲酸酯的晶体结构, 晶体属于三斜晶系, 空间群, 晶胞参数为: a＝0.73482(15) nm, b＝1.1051(2) nm, c＝1.1209(2) nm, α＝90.32(3)°, β＝101.97(3)°, γ＝105.13(3)°, V＝0.8578(3) nm³, Z＝2, D_c＝1.357 g/cm³, F(000)＝368, µ＝0.324 mm^－1. 生物测试结果显示这5种有机化合物都具有杀菌性和植物生长调节活性     

利用工业废弃物中获得的(R)-5-甲基-δ-戊酸内酯为原料合成(2R,6R)-2,6,10-三甲基十一醇

(2R,6R)-2,6,10-三甲基十一醇(1)是维生素E、维生素K和植醇的基本结构单元. 利用从甾体皂甙元氧化降解产生的工业废弃物中所获得的手性化合物(R)-5-甲基-δ-戊酸内酯(6), 先将其转化成为化学性质稳定的(4R)-甲基-5-甲氧甲氧基戊酸甲酯(7), 再经十二步反应, 以14.1%的总收率合成得到了目标化合物(2R,6R)-2,6,10-三甲基十一醇(1).     

5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌和氢醌的首次全合成

以2-甲基对苯二酚和香叶基溴为起始原料, 经过酚羟基保护, 溴代, Li₂CuCl₄催化的芳基溴与Grignard试剂的偶联以及Julia偶联等一系列反应, 完成了裸鳃亚动物的代谢产物, 5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌(1)和氢醌(2)的首次全合成, 将1用NaBH₄还原, 得到(±)-3, (±)-3也是此类天然产物之一.     

(αE,E)-α-(甲氧亚氨基)-2-[1-(芳香醛酮肟氧基)甲基]苯乙酸甲酯的立体选择性合成及生物活性研究

使用邻甲苯基重氮盐与乙醛酸甲酯肟偶联反应高立体选择性合成出 (E)-2-(羟基亚氨基)-2-邻甲基苯乙酸甲酯,经硫酸二甲酯的甲基化反应可得到重要的中间体(E)-2-(甲氧亚氨基)-2-邻甲基苯乙酸甲酯, 再经NBS溴化后与 (E)-芳香醛酮肟进行醚化反应最终得到目标物(αE,E)-α-(甲氧亚氨基)-2-[1-(芳香醛酮肟氧基)甲基]苯乙酸甲酯, 这些化合物多数具有很好的广谱杀菌活性.     

N,N'-二(二乙氧基硫代磷酰基)-1,4-苯二胺的合成、晶体结构及热性能研究

通过二乙氧基硫代磷酰氯与对苯二胺反应生成了标题化合物N,N'-二(二乙氧基硫代磷酰基)-1,4-苯二胺，并应用元素分析, FTIR及¹H NMR对标题化合物进行了表征. 利用X射线单晶衍射测定了其晶体结构, 同时应用TG分析法对其热性能进行了分析. 标题化合物的相对分子质量M_r＝412.42, 为正交晶系, Pbca空间群, 晶胞参数为a＝0.86936(16) nm, b＝1.2787(2) nm, c＝1.8897(3) nm, β＝90°, V＝2.1006(7) nm³, Z＝8, D_c＝1.304 g/cm³, μ(Mo Kα)＝0.425 mm^－1, F(000)＝872, S＝1.052. 最终偏离因子R＝0.0628, wR＝0.1860, 可观测衍射点1852个[I＞2σ(I)]. 该晶体通过对苯二胺连接并以中心对称分布, 并形成层状结构, 且存在弱的分子内氢键N—H…S. TG分析表明该化合物有很好的热稳定性及成炭性, 通过其阻燃聚丙烯腈表明, 该物质是一种高效能的膨胀型阻燃剂.     

N,N'-二茂铁甲基-(1S,2S)-1,2-二苯基乙二胺的合成及其在烯烃的不对称双羟基化反应中的应用

(1S,2S)-1,2-二苯基乙二胺和甲酰基二茂铁经缩合和还原两步反应, 以90%的产率合成了N,N'-二茂铁甲基-(1S,2S)-1,2-二苯基乙二胺, 并以其为配体催化烯烃的不对称双羟基化反应, 获得了较高的对映选择性(71%～86% ee).     

(S)-和(R)-普萘洛尔的不对称合成

普萘洛尔是一种临床上广泛使用的β受体阻断剂, 介绍了一种不对称合成(S)-和(R)-普萘洛尔的方法. 以手性Salen-Co^III催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯度的(S)-环氧氯丙烷和(R)-3-氯-1,2-丙二醇, 以(S)-环氧氯丙烷为手性原料先水解得(S)-3-氯-1,2-丙二醇, 其与1-萘酚反应得(S)-3-(1-萘基)-丙烷-1,2-二醇, 再与氯化亚砜反应得环状亚硫酸酯, 最后和异丙胺作用得(S)-普萘洛尔, 总收率80.9%, 光学纯度大于99%; 而同样以(S)-环氧氯丙烷为手性原料直接与1-萘酚反应得(2R)-3-(1-萘氧基)-1,2-环氧丙烷, 再与异丙胺作用得(R)-普萘洛尔, 总收率74.5%, 光学纯度大于99%.     

α-亚胺酮的不对称转移氢化合成(R)-沙丁胺醇

用手性(S,S)-Ru-TsDPEN催化剂不对称转移氢化α-亚胺酮化合物5-[(1,1-二甲基乙基)亚胺基]乙酰基-2-羟基苯甲酸甲酯(2)得光学纯β-氨基芳基乙醇类化合物(R)-5-[2-[(1,1-二甲基乙基)氨基]-1-羟乙基]-2-羟基苯甲酸甲酯(3), 再经一步还原反应即得(R)-(－)-沙丁胺醇. 对反应关键一步α-亚胺酮的不对称转移氢化反应条件进行了研究.     

氯化铯催化芳硒化钠对炔硒醚加成合成(Z)-1,2-二芳硒基烯

氯化铯催化下, 以商业DMF作溶剂, 芳硒化钠与炔硒醚在室温、氮气保护下反应, 立体选择地生成(Z)-1,2-二芳硒基烯.     

松毛虫性信息素(5Z,7E)-十二碳二烯醇的立体选择性合成

从简单原料乙炔出发,通过炔对丙烯醛的加成反应得到7-溴代-(4Z,6E)-庚二烯醛,再经乙二醇保护、Pd催化偶联、水解、Wittig反应和还原等步骤,立体选择性地得到松毛虫性信息素(5Z,7E)-十二碳二烯醇,其结构通过IR,NMR和MS等技术得到确认.     

气相色谱-质谱法研究多卤代产物的组成和结构

在制备取代的１,４－己二烯过程中,在钯（Ⅱ）催化下烯丙基溴对１,４－二氯－２－丁炔的加成反应生成了一系列未曾预料的复杂产物,运用气相色谱－质谱法（ＧＣ－ＭＳ）对产物进行了逐个分析。分析结果显示：（１）８个化合物中除两个为预期产物外,其余均为氯和溴交换反应的副产物,并且８个化合物中的每两个为一对几何异构体;（２）４对几何异构体中Ｚ／Ｅ的比例随着分子量的增加而逐渐下降。     

经由胂叶立德立体有择合成仿保幼激素──增丝素（ZR－512）及其（2Z，4E）－异构体

３－甲基－２－丁烯酸乙酯４经ＳｅＯ２反式氧化、还原、溴化得到关键中间体４－溴－３－甲基－（２Ｅ）－丁烯酸乙酯７．７与三苯基胂反应生成季８．二氢香茅醛与８在Ｋ＿２ＣＯ＿３－乙醇－微量水的存在下反应，得到（２Ｅ，４Ｅ）－３，７，１１－三甲基－２，４－十二碳二烯酸乙酯１ａ及其（２Ｚ，４Ｅ）－异构体１ｂ，产率７４％。该反应具有（４Ｅ）－立体选择性，同时Ｃ－２双键发生部分构型转化。     

Highly stereoselective synthesis of (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated esters and (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated amides from 1-bromo-1-fluoroalkenes via palladium-catalyzed carbonylation reactions

The highly stereoselective synthesis of (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated esters and (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated amides is described. 1-Bromo-1-fluoroalkenes (E/Z approximately 1:1), which are readily available starting materials, have been found to isomerize to high E/Z ratios after storage at -20 degrees C for 1 week or by photolysis at 254 nm. Since the (E)-isomers have been found to react faster than the corresponding (Z)-isomers at room temperature in Pd(0)-catalyzed reactions, the palladium-catalyzed carboalkoxylation of high E/Z 1-bromo-1-fluoroalkenes lead to a high Z/E (Z/E >/= 98:2) ratio of the alpha-fluoro-alpha,beta-unsaturated esters. When 1-bromo-1-fluoroalkenes (E/Z approximately 1:1) were reacted with HCOOH/NBu(3)/Pd(II)/DMF, the (E)-isomer was selectively reduced, and the remaining (Z)-1-bromo-1-fluoroalkenes were recovered in essentially pure isomeric form. The resulting mixture of (Z)-1-bromo-1-fluoroalkenes and the reduced products underwent similar palladium-catalyzed carboalkoxylation reactions at 70 degrees C, and the (E)-alpha-fluoro-alpha,beta-unsaturated esters were stereospecifically obtained. This methodology was also successfully applied for the stereospecific synthesis of (Z)- and (E)-alpha-fluoro-alpha,beta-unsaturated amides: the palladium-catalyzed carboamidation reaction of high E/Z and (Z)-1-bromo-1-fluoroalkenes lead to pure (Z)- and (E)-alpha-fluoro-alpha,beta-unsaturated amides, respectively.     

Synthesis of (+/-)-bakkenolide-A and its C-7, C-10, and C-7,10 epimers by means of an intramolecular Diels-Alder reaction

(+/-)-bakkenolide-A (1) was prepared in five steps from ethyl 4-benzyloxyacetoacetate by sequential alkylations with tiglyl bromide and (Z)-5-bromo-1,3-pentadiene, followed by an intramolecular Diels-Alder reaction of (E,Z)-triene 25b as the key step. The hydrindane cycloadduct 28 was subjected to hydrogenation and spontaneous or acid-catalyzed lactonization, followed by a Witttig reaction to introduce the exocyclic methylene group of 1. The known 7-epibakkenolide-A (2) and novel 10-epi- and 7,10-diepibakkenolide-A (3 and 4, respectively) stereoisomers were obtained as minor byproducts. When (E)-5-bromo-1,3-pentadiene was used instead of the Z-isomer, the 10-epi- and 7,10-diepibakkenolides were the major products. In both cases exo cyclization was preferred over endo. An alternative approach was based on a similar intramolecular Diels-Alder cycloaddition, using dimethyl malonate instead of ethyl 4-benzyloxyacetoacetate as the starting material for the double alkylation preceding the cycloaddition step. The cycloadduct was then converted into the corresponding alpha-phenylseleno propargyl esters 16 or 22. However, attempted formation of the spiro center by a radical cyclization resulted chiefly in reductive deselenization.     

Synthesis of the N-((1E)-alkenyl)-(2Z,4Z)-heptadienamide side chain of salicylihalamide A and apicularens A and B

[reaction: see text] The unstable N-((1E)-alkenyl)-(2Z,4Z)-heptadienamide side chain of salicylihalamide A (1) and apicularens A and B (3 and 4) has been prepared in one pot by the addition of (1Z,3Z)-hexadienylcuprate, prepared in situ from EtLi, CuBr.SMe2, and acetylene, to a (1 E)-alkenyl isocyanate.     

Stereoselective preparation of (E)- and (Z)-alpha-fluorostilbenes via palladium-catalyzed cross-coupling reaction of high E/Z ratio and (Z)-1-bromo-1-fluoroalkenes

A highly stereoselective method to prepare both (E)- and (Z)-alpha-fluorostilbenes is described. 1-Bromo-1-fluoroalkenes (E/Z approximately 1:1), a readily available starting material, isomerizes to high E/Z ratios by storage at -20 degrees C or by photolysis at 254 nm. Stille coupling between these high E/Z 1-bromo-1-fluoroalkenes and aryl stannanes gave (Z)-alpha-fluorostilbenes in high stereoselectivity. (Z)-1-Bromo-1-fluoroalkenes, which were kinetically separated from 1-bromo-1-fluoroalkenes (E/Z approximately 1:1), can participate in Suzuki coupling reactions to give (E)-alpha-fluorostilbenes stereoselectively.     

P(CH(3)NCH(2)CH(2))(3)N as a dehydrobromination reagent: synthesis of vitamin A derivatives revisited.

Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.     

Novel Aplysinopsin-Type Alkaloids from Scleractinian Corals of the Family Dendrophylliidae of the Mediterranean and the Philippines. Configurational-assignment criteria,stereospecific synthesis,and photoisomerization

From the scleractinian coral Tubastraea sp. (Dendrophylliidae) collected at Palawan, Philippines, 3′-deimino-3′-oxoaplysinopsin ( 4 ) and 6-bromo-3′-deimino-3′-oxoaplysinopsin ( 6 ) are now isolated as 5:2 mixtures of (E/Z) stereoisomers. The 3′-deimino-2′,4′-bis(demethyl)-3′-oxoaplysinopsin ( 7 ) and 6-bromo-3′-demino-2′,4-bis(demethyl)-3′-oxoaplysinopsin ( 5 ) are isolated as 2:3 and 1:1 (E/Z) mixtures, respectively, from another dendrophylliid, Leptopsammia pruvoti, collected near Marseille, Mediterranean coast of France. Larger amounts of these and related compounds, needed for a full structural determination, are obtained by synthesis. Thus, condensations of indol-3-carboxaldehyde (9) or of its 6-bromo derivative 14 with hydantoin (15) , 3-methylhydantoin (11) , or 1,3dimethylhydantoin (10) give the prevalent natural aplysinopsins with high stereospecificity. The minor stereoisomers (Z)- 4 , (Z)- 6 , (E)- 7 , and (E)- 5 are obtained by (E/Z) photoisomerization under UV light of the condensation mixtures. The configuration is assigned from larger H? C(8)/C(5′) ¹H, ¹³C couplings in the (E) than in the (Z) isomer, and, in the case of 4 and 6 , from NOE enhancement at Me? N(2′) on irradiation at H? C(8). The stereospecificity of the condensations is attributed to steric inhibition to planarity in the rate-limiting transition states, due to N(2′)/H? C(2) repulsion with (Z)- 4 and (Z)- 6 , or to C(5′)?O/H? C(2) repulsion with (E)–7 or (E)- 5 . As the aplysinopsins undergo (E/Z ) phostoisomerization also under the daylight conditions of the laboratory, their isomeric composition in nature can not be presently assessed.     

A stereoselective route to alkenyl sulfides through the palladium-catalyzed cross-coupling reaction of 9-alkyl-BBN with 1-bromo-1-phenylthioethene or (E)- and (Z)-2-bromo-1-phenylthio-1-alkenes

The reaction of 9-alkyl-9-BBNs with 1-bromo-1-phenylthioethene or (E)- and (Z)-2-bromo-1-phenylthio-1-alkenes takes place readily in the presence of Pd(PPh₃)₄ and sodium hydroxide to afford stereodefined vinylic sulfides in excellent yields.