苯甲酰氧基取代的2-吡喃酮的固相光二聚反应

以二苯甲酮为光敏化剂,C4-位苯甲酰氧基取代的6-甲基-2-吡喃酮(1)的固相光二聚反应穿过1的C3-C4双键高选择性地发生[2+2]环加成反应合成了anti头-头二聚物(2),其结构经1H NMR,FI-IR,MS和元素分析表征。反应机理利用WINMOPAC PM5方法推定。     

5-甲基-1,2,4-三唑-3-硫酮类糖苷化合物的合成及抗菌活性

在KOH/丙酮体系中, 以5-甲基-4-N-取代苯基亚胺/胺基-1,2,4-三唑-3-硫酮为原料, 与溴-α-D-四乙酰葡萄糖进行Kenigs-Knorr反应合成了10个新颖的化合物—5-甲基-4-N-取代苯基亚胺基/胺基-3-S-(2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基)-1,2,4-三唑(2a~2e, 5a~5e); 并在二氯甲烷/甲醇/甲醇钠混合体系中水解脱除乙酰基, 得到10个新颖的化合物—5-甲基-4-N-取代苯基亚胺基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(3a~3e)及5-甲基-4-N-取代苯基胺基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(6a~6e). 化合物的结构均经核磁共振波谱(NMR)、 红外光谱(IR)和高分辨质谱(HRMS)分析确证. 生物活性测试结果表明, 目标化合物对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠球菌普遍具有较好的抗菌活性. 化合物3d和3e对4种菌株的最小抑菌浓度相对较低, 表现出较强的广谱抗菌活性.     

新型5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d] 嘧啶-4-酮衍生物的合成及其除草活性

以吡唑膦亚胺、芳基异氰酸酯和芳基甲酰肼为原料，通过串联氮杂Wittig反应关环合成了12种新型的5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d]嘧啶-4-酮衍生物(3a~3l)，其结构经¹H NMR, ¹³C NMR， IR和HR-MS(ESI)表征。对单双子叶除草活性的初步测试结果发现：部分化合物具有优异的除草活性，特别是浓度为100 mg·L^-1时，5-(4-氟苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4(5H)-酮3i和5-(4-吡啶苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4 (5H)-酮3k对油菜和稗草的茎和根的抑制率高达100%。     

D-氨基葡萄糖合成3-苯甲酰胺基-5-乙酰基呋喃

以可再生性D-氨基葡萄糖为底物,在甲醇-三乙胺体系中,以苯甲酰氯作为酰化试剂,经选择性N-酰化反应合成得到N-苯甲酰基-D-氨基葡萄糖,继续在硼酸催化下,转化为3-苯甲酰胺基-5-乙酰基呋喃,两步一锅煮总产率则为44%,其结构经¹H NMR,¹³C NMR, IR和MS(ESI)确证。      

无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应

开发了无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2,2-二氟乙基-1-胺的串联反应.应用该反应在甲醇中回流,以39%~83%的收率合成了一系列4-(N-(2,2-二氟乙基)(N-杂环芳基甲基)氨基)-5,5-二取代呋喃-2(5H)-酮,其结构经1H NMR,13C NMR和HR-ESI-MS表征,并进一步通过3-氯-4-(N-2,2-二氟乙基)(N-嘧啶-5-基甲基胺基)-5,5-螺(4-甲氧基环己基)呋喃-2(5H)-酮(8)的晶体衍射间接证实.测试了所合成化合物的生物活性,结果表明,在600μg·mL^-1浓度时4-(N-2,2-二氟乙基)(N-6-氯吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3a)和4-(N-2,2-二.氟乙基)(N-6-氟吡啶-3-基甲基胺基)-5,5-二甲基呋喃-2(5H)-酮(3c)对桃蚜的死亡率均为100%.     

三-2-吡喃酮与二苯酮的固相[2+2]光环加成反应

4-羟基-6-甲基-2-吡喃酮分别与原甲酸三氯乙酯,三(溴甲基)氧磷和1,3,5-三(溴甲基)苯经取代反应制得三-2-吡喃酮(3a~3c);3a和3b分别与二苯酮(4)通过经历4的三线激发态,横穿3的C5-C6,C5'-C6'和C5″-C6″双键经固相[2+2]光环加成反应,高位置、高配向选择性地合成了4个新型的氧杂类化合物(5a,5a',5b和5b'),其结构经1H NMR,13C NMR,IR,LR-MS和HR-MS表征。     

新型1,3,4-噁二唑-2-硫酮衍生物的合成及其抗肿瘤活性

以手性氨基酸和间甲基苯甲酸(或苯乙酸)为原料,经酯化、缩合、肼解和环合反应合成了12个新型的1,3,4-噁二唑-2-硫酮衍生物(6a~6f或7a~7f),其结构经1H NMR,FT-IR和ESI-MS表征。用MTT法研究了6和7的抗肿瘤活性。结果表明:(2S)-5-(3-甲基苯甲酰胺基)苯乙基-1,3,4-噁二唑-2-硫酮(6f)和(2S)-5-(2-羟基-苯乙酰胺基)乙基-1,3,4-噁二唑-2-硫酮(7b)对红白血病细胞(K562)抑制活性较好。     

3",3"-二甲基吡喃[3',4']2,4,2'-三羟基查尔酮的首次全合成

以2,4---羟基苯乙酮和2,4-二羟基苯甲醛为起始原料,经过C-异戊烯基化、保护酚羟基、羟醛缩合、去保护基反应首次成功地完成了天然产物3",3"-二甲基吡喃[3’,4’]2,4,2’-三羟基查尔酮的全合成,总产率18.4％,其结构经1H NMR,IR和MS表征.中间体8未见文献报道.     

(±)-2-甲基-5-羟基-2-(4'-甲基-3'-戊烯基)-二氢-1-苯并吡喃黄烷酮的全合成

以2,4,6-三羟基苯乙酮和柠檬醛为起始原料,经环化、保护酚羟基、羟醛缩合、脱保护、催化环化等反应以5.9%的总产率完成了天然产物(±)-2-甲基-5-羟基-2-(4'-甲基-3'-戊烯基)-二氢-1-苯并吡喃黄烷酮的全合成,其结构经1H NMR,13C NMR和HR-ESI-MS确证。     

微波辐射下合成2-(未)取代苯甲酰胺基-5-(1-苯基-3-甲基-5-氯吡唑- 4-基)-1,3,4-噻二唑衍生物

分别在微波辐射和常规加热条件下, 通过2-氨基-5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑(1)与(未)取代苯甲酰氯(2a～2j)反应, 合成了一系列未见文献报道的2-(未)取代苯甲酰胺基-5-(1-苯基-3-甲基-5-氯吡唑-4-基)-1,3,4-噻二唑衍生物(3a～3j). 标题化合物的结构经元素分析, IR, 1H NMR确证.     

2-Benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxy-carbonylvinyl-1 as N-protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N-terminal 3-heteroarylamino-2,3-dehydroalanine

Ethyl 2-benzoyl-3-dimethylaminopropenoate ( 6 ) and methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with α-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-α-amino acids 13–19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycar-bonylvinyl-1)-protected dipeptide esters 20–31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo-rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) by glycine gave N-(2-benzoylamino-2-methoxycar-bonylvinyl-1)glycine ( 47 ), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester ( 48 ). Treatment of 48 with 2-arnino-4,6-dirnethylpyrimi-dine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71–82, and pentapeptide esters 83–85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58–85.     

The synthesis of 5-substituted 3-benzoylamino-6-(2-substituted amino-1-ethenyl)-2H-pyran-2-ones and their transformations into 2H-pyrano[3,2-c]pyridine derivatives

A new approach to the 2H-pyrano[3,2-c]pyridine system is described. 5,6-Disubstituted 3-benzoylamino-2H-pyran-2-ones 3a,b , prepared from the corresponding 1,3-dicarbonyl compounds 1a,b and methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate ( 2 ), were converted into 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 4a ) and 5-acetyl derivative 4b . The exchange of the dimethylamino group in 4a,b with aromatic amines 5a-f,m , héteroaromatic amines 5g-i , and benzylamines 5j-l produced 5-ethoxycarbonyl-3-benzoylamino-6-(2-arylamino- or heteroarylamino-or benzylamino-1-ethenyl)-2H-pyran-2-ones 6a-l , and its 5-acetyl analog 6m . The compounds 6 were cyclized in basic media into 2H-pyrano[3,2-c]pyridine derivatives 7a-h . Analogously react also α-amino acid derivatives 8a-c and 11 as nitrogen nucleophiles producing 9a-c, 10 and 12 .     

New,Convenient, One-Pot Method for the Synthesis of Thiazolyl-pyrazolones from Dehydroacetic Acid Derivative via a Multicomponent Approach

A convenient one-pot method for the synthesis of thiazolyl-pyrazolones was described in excellent yields. Reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one with thiosemicarbazide and ethyl 2-(2-arylhydrazono)-3-oxobutanoates in anhydrous ethanol under reflux conditions afforded the corresponding 4-(2-arylhydrazono)-1-(4-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)thiazol-2-yl)-3-methyl-1H-pyrazol-5(4H)-one in good yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, infrared, ¹H NMR, and mass spectroscopic studies.     

Rearrangements of 5-acetyl-3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-2H-pyran-2-one and 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one into 1-aminopyridine,pyrano[2,3-b]pyridine and isoxazole derivatives

Rearrangements of 5-acetyl-3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-2H-pyran-2-one ( 1 ) and 3-benzoylamino-6-(2-dimethylamino-1-ethenyl)-5-ethoxycarbonyl-2H-pyran-2-one ( 7 ) in the presence of N-nucleophiles, such as ammonia, hydrazine, and hydroxylamine, into 1-aminopyridine, pyrano[2,3-b]-pyridine, and isoxazole derivatives 5, 11 , and 15 is described. In the reaction of compounds 1 and 7 with C-nucleophiles, such as 5,5-dimethyl-1,3-cyclohexanedione and barbituric acid, only substitution of the dimethylamino group is taking place to give the compounds 17, 18 , and 20 .     

Transformation of 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone into methyl 2-benzoylamino-3-oxobutanoate. The synthesis of 1-substituted 4-benzoylamino-3-methyl-5(2H)-pyrazolones

Methyl 2-benzoylamino-3-oxobutanoate ( 3 ) was prepared from hippuric acid (1) which was converted with N,N-dimethylacetamide and phosphorus oxychloride into 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 2 ) followed by hydrolysis with hydrochloric acid in methanol. Compound 3 was treated with hydrazines 4 to give 4-benzoylamino-3-methyl-1H-pyrazol-5(2H)-one ( 6a ) and its 1-substituted derivatives 6b-j . The corresponding hydrazones 5f, i, j were isolated as intermediates.     

Combinatorial solution-phase synthesis of alkyl (1S*,2S*,3R*,5R*,6R*)-1-alkyl-3-aryl-6-benzoylamino-1-hydroxy-7- oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-2-carboxylates

Combinatorial solution-phase cycloadditions of (1Z,4R*,5R*)-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines 3 to beta-keto esters 4 afforded a library of 26 bicyclic pyrazolidinones 5 in 6-89% yields and in 14-100% de. All products were isolated in >90% purity according to 1H NMR, and 25 of them were analytically pure. The structures of cycloadducts were confirmed by NMR and X-ray diffraction. Most of the products were isolated as mixtures of the major (1S*,2S*,3R*,5R*,6R*)-epimers 5 and the minor (1R*,2S*,3R*,5R*,6R*)-epimers 6. Epimerization of cycloadducts 5/6 at the anomeric position 1 in solution was confirmed by 1H NMR.     

An Efficient Synthesis of 8-Amino-9-Benzylguanine

The reaction of 2,5-diamino-4-benzylamino-pyrimidin-6(III)-one (6) with benzoyl isothiocyanate furnished 2-amino-4-benzylamino-5-[1-(3-benzoylthioureido)]-pyrimidin-6(1H)-one (7) in good yield. The title compound I was synthesized from compound 7 via a cyclodesulfurative reaction with DCC in DMF at 80°C directly to form 8-benzoylamino-9-benzylguanine (9) which was subsequently treated with 1 N sodium hydroxide.     

Syntheses of Benzoxepinoquinolinone and Benzothiepinoquinolinone

l-Benzoxepino(3, 4-b)quinolin-l3(6H)-one and its halogen,alkyl, alkoxy derivatives Va'-d' and 1-benzothiepino(3,4-b}-quinolin- 13 ( 6H)-one Vf, and its alkyl derivatives Vg, weresynthesized through cyclization of 2-(substituted phenoxymethyl)-3-quinolinecarboxylic acids Va-d and 2-[ (un)substituted phen-ylthiomethyll-3-quinolinecarboxylic acids IVf-g in the presence ofpolyphosphoric acid.The acids IV were obtained from the corresponding ethyl-esters @ whcih were prepared through refluxing ethyl 2-bromo-methyl-3-quinolinecarboxylate(1) with substituted phenol or (un)substituted thiophenol in the presence of NaOEt.The compound Vg, was allowed to react with NBS, KaBH4, NH2OH-HCl to give compounds VII , VIII, and IX, respectively.The structures of 24 new compounds have been confirmed by elemental analysis, IR and 1H NMR.     

Reformatsky reaction of methyl 1-bromocycloalkane-1-carboxylates with phenyl-and benzoylhydrazones derived from aromatic aldehydes

Reformatsky reagents obtained from methyl 1-bromocyclohexane-and 1-bromocyclopentane-1-carboxylates reacted with aromatic aldehyde phenyl-and benzoylhydrazones to give 3-aryl-2-phenylamino-2-azaspiro[3.5]nonan-, 3-aryl-2-phenylamino-2-azaspiro[3.4]octan-, 3-aryl-2-benzoylamino-2-azaspiro[3.5]-nonan-, and 3-aryl-2-benzoylamino-2-azaspiro[3.4]octan-1-ones, respectively. The reaction of furan-2-carbaldehyde phenylhydrazone with methyl 1-bromocyclohexane-1-carboxylate and zinc led to the formation of 4-(2-furyl)-2-phenyl-2,3-diazaspiro[4.5]decan-1-one.