Didemnaketal A类似物的合成研究──C8-C15中间体的合成

DidemnaketalA是一类具有明显抗艾滋病活性的天然螺环缩酮类化合物^[1],但至今未见有关合成及立体化学研究的报道.为进一步研究这类螺环缩酮类化合物的生理活性,我们开展了侧链简化的类似物(如化合物1)的合成研究.     

茼蒿素类似物的分子多样性2-(Z)-亚苄基-1,6,9-三氧杂螺环 [4,5-癸-3-烯类化 合物的合成

有多种生物活性的茼蒿素类似物是一类具有螺环缩酮烯醚独特结构的化合物。本文报道用糠醇为原料,以我们的呋喃二醇脱水－螺环缩酮化反应为关键反应,合成了一类三氧杂螺环-[4,5]-癸烯的新型茼蒿素类似物。为这类化合物分子多样性开辟了新的途径。     

微波作用下3-取代-(1H)-嘧啶［1，2-a］喹啉-1-酮的一步合成法

5-(双甲硫基亚甲基 ) -2 ,2 -二甲基 -1 ,3 -二环己 -1 ,4-二酮 (1 ) [1] 既具有丙二酸亚异丙酯的环状结构 ,又具有乙烯基硫代缩酮的结构特征 .它是一种多功能的合成试剂 ,其最重要性质是可与多种亲核试剂发生加成反应 ,继而消除甲硫基 ,从而可以转变成一系列有用的合成中间体 (2 ) [2～ 5] .若亲核试剂具有两个亲核部位 Nu1及 Nu2 ,则 Nu1反应后 ,Nu2可进一步与丙二酸亚异丙酯的羰基进行分子内的亲核加成 ,从而形成环状化合物 (3 ) ,这一模式已在多种杂环化合物合成中获得应用[6～ 8] .Me SMe SOOMe OOMe　+ Nu1-Nu Me SNu1Nu …     

螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的改进合成

以2,4-二氧代戊酸甲酯(1)和1,5-二甲基-6-亚甲基环己烯(2)为原料,通过[2+2]光环加成和retro-Benzilicacid重排,合成了具有螺[4,5]癸烷结构的岩兰烷基本碳架的化合物3.用锌粉选择还原五元环上碳碳双键得螺环二酮(4),对环外羰基实施保护并将环上酮基转化为亚甲基得到重要的合成前体6,经与甲基溴化镁的格氏反应生成混合的标题化合物.利用羟基和异氰酸苯酯的反应生成一对N-苯基氨基甲酸酯异构体(12),二者分离后经四氢铝锂还原,完成了螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的全合成.     

螺环倍半萜(±)-α-花柏烯-3-酮的全合成

通过萜品油烯 ( Terpinolene)与 2 ,4-二氧代戊酸甲酯的 de Mayo反应得到 [2 +2 ]光加成产物 ,经反aldol重排 ,再环合成具有螺 [5 ,5 ]十一烷结构的花柏烯基本碳架 ,进而对其官能团进行化学修饰 ,完成了螺环倍半萜 (± ) -α-花柏烯 -3 -酮的全合成 .     

不饱和螺环缩酮的合成及对桔小实蝇(Bactrocera dorsalis)性引诱活性与构效关系研究（英文）

螺环缩酮结构片段广泛存在于许多具有不同来源的生物活性天然产物中,该片段往往对生物活性起着重要作用.合成了两类结构新颖的螺环缩酮类化合物,并以甲基丁香酚为标准品对照,测试其对桔小实蝇(Bactrocera dorsalis)的电生理活性.结果表明:雄性和雌性桔蝇对大部分化合物小实有明显的电生理响应.螺环缩酮的立体化学和其苯环上取代基对电生理响应有一定的影响.     

光/电化学驱动螺环化合物的合成研究进展

螺环作为一种重要的有机分子骨架,在有机化学、药物化学、材料科学等领域中广泛存在.由于螺环骨架具有较大的三维空间结构,满足药物设计中对构象刚性的需求,因此开发高效的螺环化合物的合成方法尤为重要.近年来,光催化和电催化作为绿色、高效的合成手段,为螺环化合物的合成注入了新的潜力.主要按螺[4.5]类骨架、螺[5.5]类骨架、螺[2.3]类骨架以及螺吲哚类骨架的构建进行了分类,并从光催化和电催化合成两个方面对螺环化合物的构建进行了综述.     

催化不对称[8+2]环加成反应构建环庚三烯并吡咯烷-3,3'-吲哚酮

设计了azaheptafulvenes作为偶极子与N-Boc-3-烯基吲哚酮反应,用来构建螺环[吡咯烷-3,3'-吲哚酮]衍生物.在1mol%手性氮氧-Ni(II)配合物催化剂条件下,该不对称[8+2]环加成反应以高的收率(90%~99%收率),好的非对映选择性(高达97∶3 dr)和优异的对映选择性(92%~99%ee)得到手性环庚三烯并螺环[吡咯烷-3,3'-吲哚酮]衍生物.     

α,β,γ,δ-四-{4-13-(9-(4-(3-(9-(4-(2-(5,5-二酰氧基甲基-1,3-二噁烷基))))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基)))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基]}苯基卟啉星形化合物的合成

以对苯二甲醛、丙二腈、季戊四醇和毗咯为原料,合成了含有螺环结构单元的中间体3-[4-(2,2-二氰基)乙烯基]苯基-9-(4-甲酰基)苯基-2,4,8,10-四氧杂螺[5.5]十一烷(3)和α,β,γ,δ-四-(4-甲酰基苯基)卟啉(4).4与过量的季戊四醇反应,得到α,β,γ,δ-四-{4-[2-(5,5-二羟甲基-1,3-二噁烷基)]}苯基卟啉(5),5与3的反应产物经10%NaOH处理后,再与过量的季戊四醇反应,得到α,β,γ,δ-四-{4-[3-(9-(4-(3-(9-(4-(2-(5,5-二羟甲基-1,3-二噁烷基))))苯基一2,4,8,10.四氧杂螺[5.5]十一烷基)))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基]]苯基卟啉(6),6与乙酐、丙酐、苯甲酰氯反应,得到α,β,γ,δ-四-{4-[3-(9-(4-(3-(9-(4-(2-(5,5-二乙酰氧基甲基-1,3-二噁烷基))))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基)))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基])苯基卟啉(7),α,β,γ,δ-四-{4-[3-(9-(4-(3-(9-(4-(2-(5,5-二丙酰氧基甲基-1,3-二噁烷基))))苯基.2,4,8,10-四氧杂螺[5.5]十一烷基)))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基]}苯基卟啉(8)和α,β,γ,δ-四-{4-[3-(9-(4-(3-(9-(4-(2-(5,5-二苯甲酰氧基甲基-1,3-二噁烷基))))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基)))苯基-2,4,8,10-四氧杂螺[5.5]十一烷基]}苯基卟啉(9)等三种卟啉星形化合物.中间体1～6和星形化合物7～9均进行了IR,1H NMR,MS和元素分析等结构表征.对影响反应的诸因素进行了讨论.     

基于[3+2]环加成反应的氮杂螺[3,4]环辛烷的合成

哌嗪、吗啉是小分子药物中常见的结构片段,2,6-二氮杂螺[3,4]环辛烷和2-氧-6-氮杂螺[3,4]环辛烷等四元螺环化合物作为其类似物,在药物化学领域具有良好的应用前景.本研究以廉价易得的丙二酸二乙酯或丙烯酸乙酯为起始原料,经[3+2]环加成反应,可便捷高效地完成6-苄基-2,6-二氮杂螺[3,4]环辛烷和2-氧-6-氮杂螺[3,4]环辛烷克级水平的合成.     

Acid catalysed novel rearrangement of bicyclic dienone

The dienone (4) on heating with methanolic hydrochloric acid underwent ring cleavage yielding the aromatic ketal (6) which on acid hydrolysis produced the aldehyde (7). Similar treatment of the dienone (4) with acetic anhydride and p-toluenesulfonic acid furnished the ester (8) which on alkaline hydrolysis afforded the dimeric product (10). The structure of the products (6), (7), (8) and (10) are defined on the basis of the spectral evidence.     

Synthesis of Tricyclo [6.2.1.01,5]undecadiones via Intramolecular Photoaddition of 5-(1-Cyclopentenylmethyl)-3-alkoxy-2-cyclopentenones

Irradiation of the dienone methyl ether 3a furnished the unstable regioisomeric photoadducts 4a and 5a which on Lewis acid-catalyzed fragmentation afforded the tricyclic diketones 6,7 and 8 . The same mixture was obtained from the isobutyl ether 3b (Scheme 2).     

Syntheses of anomerically phosphodiester-linked oligomers of the repeating units of the Haemophilus influenzae types c and f capsular polysaccharides

Spacer-equipped dimers and trimers of the repeating units of the capsular polysaccharide of Haemophilus influenzae type c, -4)-3-O-Ac-beta-D-GlcpNAc-(1-->3)-alpha-D-Galp-(1-OPO(3-)-, and type f, -3)-beta-D-GalpNAc-(1-->4)-3-O-Ac-alpha-D-GalpNAc-(1-OPO(3-)-, have been synthesized for use in immunological studies. H-Phosphonate chemistry was used for the formation of the interglycosidic phosphate diester linkages. Two types of building blocks, a spacer glycoside disaccharide starting monomer (15 and 22) and an anomeric monoester alpha-H-phosphonate disaccharide elongating monomer (12 and 27), were built up for each serotype structure from properly protected monosaccharide precursors using mainly thioglycosides as glycosyl donors. Stereospecificity in the formation of the alpha-linked monoester H-phosphonate was possible in type c through crystallization of the pure alpha-anomer of the precursor hemiacetal from an alpha/beta-mixture, whereas in type f, the hemiacetal was isolated directly as exclusively the alpha-anomer. Subsequent phosphonylation using triimidazolylphosphine was performed without anomerization. Formation of the anomeric phosphate diester linkages was performed using pivaloyl chloride as coupling reagent followed by I(2)/H(2)O oxidation of the formed diester H-phosphonates. Original experiments afforded no diester product at all, but optimization of the oxidation conditions (lowering the temperature and dilution with pyridine prior to I(2) addition) gave the dimers in good yields (71% and 81%) and, subsequently, after removal of a temporary silyl protecting group in the dimers, the trimers in fair yields (36% and 37%), accompanied by hydrolysis of the dimer phosphate linkage. One-step deprotection through catalytic hydrogenolysis efficiently afforded the target dimer (30 and 36) and trimer structures (32 and 39). The synthetic scheme allows for further elongation to give higher oligomers.     

Polyfluoro-compounds based on the cycloheptane ring system. Part 7. Ethoxypolyfluorocycloheptenes and polyfluorocycloheptenones

Dodecafluorocycloheptene and ethanolic potassium hydroxide afforded 1- ethoxyundecafluorocycloheptene which at 410°C decomposed to decafluorocyclohept-2-enone. Decafluorohepta-l,3-diene likewise gave mainly 1-ethoxynona- fluoro-, together with some 1,4-diethoxyoctafluoro-cyclohepta-1,3-diene. The 1-ethoxy-1,3-diene was photoisomerised to 1-ethoxynonafluorobicyclo- (3,2,0)hept-6-ene (proving its structure), and was decomposed on pyrolysis at 430°C to give a complex mixture, from which octafluorocyclohepta-2,4- dienone was isolated.     

Steroidal analogues of unnatural configuration—VII : Total synthesis of 17β-hydroxy-9-methyl-9β, 10α-oestr-4-en-3-one,a novel retrotestosterone isomer

Conjugate methylation of 17β-hydroxy-des-a-oestr-9-en-5-one (1) and the derived 4,5-seco-steroid (6b) afforded the respective 9β-methyl compounds. Base-catalysed alkylation of 17β-hydroxy-9-methyl-des-a-9/gb-oestran-5-one (3a) resulted in attack at C(6); this result was used to prepare the anthrasteroid (5). Ring closure of the 9β-methyl-4,5-seco-steroid (8) derived from 6b afforded 17β-hydroxy-9-methyl-9β,10α-oestr-4-en-3-one (9a). Conjugate methylation of 17β-hydroxyoestra-4,9-dien-3-one (11) resulted in 1,4-addition to the dienone system.     

Stereospecific synthesis of dienone iron tricarbonyl complexes by friedelcrafts acylation

Acylation of diene Fe(CO)₃ complexes using the Perrier complexes RCOCl/AlCl₃ in methylene chloride at 0°C gives dienone complexes in high yield. Substitution occurs only at unsubstituted terminal carbons of the diene unit. Quenching the reaction mixtures in cold aqueous ammonia gives cis dienone complexes only. Trans dienone complexes are prepared by subsequent isomerization in methanolic sodium methoxide. Formylation of diene Fe(CO)₃ complexes proceeds in modest yield using dichloromethylmethyleter/AlCl₃ in methylene chloride to give trans-dienal complexes. Reduction of the dienone and dienal complexes as well as those of dienols and dienoic esters with 4 : 1 AlCl₃/LiAlH₄ results in complete removal of the oxygen function to give trans-diene complexes in good yield.     

The retro-Nazarov reaction

Treatment of 2-bromo-4-t-butoxy-2-cyclopentenone with an amine base in refluxing trifluoroethanol afforded a ring-opened product in moderate yield. The mechanism of the reaction has been formulated as a retro-Nazarov reaction in which an oxyallylic cation undergoes ring-opening to a dienone. Several other examples of the reaction have been established through a protocol involving the conjugate addition of an organocuprate to 2-bromo-4-t-butoxy-2-cyclopentenone followed by treatment of the adducts with base in refluxing trifluoroethanol.     

Pefluoroaralkyl ethers

Some perfluorinated ethers have been prepared containing both alkyl and aryl groups and either one or two oxygen atoms.Pentafluorophenylmagnesium bromide, with octafluoroadipoyl chloride, perfluoro-oxydiacetyl chloride and perfluoro-oxydipropionyl chloride, gave the corresponding diketones which, upon treatment with sulphur tetrafluoride, afforded perfluoro-1,6-diphenylhexane, perfluoro-bis(2-phenylethyl)ether and perfluoro-bis(3-phenylpropyl)ether, respectively.Pentafluorophenylmagnesium bromide with perfluoro-2-methyl-3-oxanonanedioyl fluoride (prepared from octafluoroadipoyl fluoride and hexafluoropropene oxide) gave a diketone which was treated with sulphur tetrafluoride to give perfluoro-2-methyl-1,9-diphenyl-3-oxanonane.Reactions between octafluoroadipoyl chloride and pentafluorophenol, nonafluoro-4-hydroxybiphenyl and perfluoro-3-hydroxy-4,4′-dimethylbiphenyl gave the corresponding diester which were then each treated with sulphur tetrafluoride and hydrogen fluoride. The first two diesters gave perfluoro-1,6-diphenoxyhexane and perfluoro-1,6-bis(4-phenylphenoxy)hexane, but the corresponding diether was not isolated from the third diester.The effect of structure upon the liquid ranges of the ethers is discussed.     

Conversion of pravastatin into an advanced intermediate for the synthesis of the HMG-CoA reductase inhibitor BB-476

Rearrangement of the decalin system of pravastatin under S_N2′ Mitsunobu conditions and subsequent selective hydrolysis and oxidation afforded a key dienone 23, which upon copper-catalyzed addition of a 1E-propenyl moiety established the carbon framework of BB-476 3 in high diastereomeric excess.     

A new approach to the synthesis of pyridazino[4,5-c]pyridazinones

The reaction of 5-hydrazinopyridazin-3(2H)-ones 1 with α-keto diester 2 in acetic acid afforded the corresponding 4,6-dihydropyridazino[4,5-c]pyridazin-5(1H)-ones 3 and pyrrolo[2,3-d)pyridazin-4(5H)-ones 4 . Compounds 3 were also obtained from 4-bromo-5-hydrazinopyridazin-3(2H)-ones 8 and 2 under milder conditions. 5-Bromo-4-hydrazinopyridazin-3(2H)-one 9 , the regioisomer of 8b , also reacted readily with 2a to give 4,7-dihydropyridazino[4,5-c]pyridazin-8(1H)-one 10b , the regioisomer of 3b .