低价钛促进的1,2-二氢喹唑啉-4(3H)-酮的合成

喹唑啉-4(3H)-酮是一类生物碱,取代喹唑啉-4(3H)-酮具有广泛的药理学活性．因而对其合成方法和合成新型喹唑啉-4(3H)-酮的衍生物的研究已成为热点．低价钛试剂是一种还原偶联试剂,它能引起醛酮的还原偶联生成烯烃,还能引起其它官能团的还原偶联反应,该反应已应用于天然产物和一些碳环化合物的合成,而用于杂环化合物的合成研究报道较少．本文报道低价钛试剂(TiCl4-Zn体系)促进的1,2-二氢喹唑啉-4(3H)-酮的合成。     

（3S）-2,2-二甲基-3-苄氧基癸酸的合成

以(R)-pantolactone为原料，经还原、羟基保护、环合、开环、脱保护、氧化等8步反应，合成了(3S)-2，2-二甲基-3-苄氧基癸酸，总收率为40．0％．     

甾体不对称合成的研究

(一)2-烷基-2-(3'-乙二醇缩酮丁基)-1,3-环戊二酮的不对称还原 甾体不对称全合成中一个重要中间体2可以由三酮化合物1经微生物不对称还原而得。为避免1在还原时所得的桥环副产物8,我们先将三酮1用乙二醇选择性地保护侧链羰基成3,然后将3用啤酒酵母还原,得到了光学活性化合物4而未分离到8。     

Kishner-Wolff改良法

研究Kishner-Wolff改良法应用于双酮,酮醇,酮酸及α,β-不饱和羰基化合物: 1.α-双酮、联苯甲酰(Ⅰ)及α-酮醇、安息香(Ⅶ)能正常还原,产率甚佳,但碱须后加.并解释α-酮醇、安息香(Ⅶ)变成对应的饱和烃二苯乙烷(Ⅱ)的反应机理. 2.α-酮酸、苯代焦葡萄酸(ⅩⅫ)及γ-酮酸苯甲酰丙酸(ⅩⅩⅩ)能正常还原,产率尚佳. 3.β-双酮、双苯甲酰甲烷(ⅩⅩⅣ),γ-双酮、双苯甲酰乙烷(ⅩⅩⅧ)及β-酮酸、苯甲酰乙酸(ⅩⅩⅥ)均不能正常还原,而得含氮环状化合物3,5-二苯基吡唑(ⅩⅩⅤ),3,6-二苯基哒嗪(ⅩⅩⅨ)及3-苯基吡唑酮(ⅩⅩⅦ). 4.α,β-不饱和醛,糠醛(XLI)及桂皮醛(XLIII)~([1c])均能正常还原,但α,β-不饱和酮,亚苄基苯乙酮(XXX)及亚苄基丙酮(XXXV)均不能正常还原,而得环丙烷衍生物,1,3-二苯基环丙烷(XXXIV)及1-苯基3-甲基环丙烷(XXXVII).至于异丙烯基丙酮(XXXVIII)则得吡唑啉化合物(XXXIX).     

利用选择性转移氢化反应合成含卤素或杂环的饱和酮

在金属前体[IrCl(COD)]2, 1,2-双(二苯基膦)乙烷(dppe)和碳酸铯的催化下,用异丙醇做氢源时,含卤素或杂环的α,β-不饱和酮可以选择性地发生1,4-还原得到饱和酮,产率高达90%.反应中未出现卤素被还原和催化剂中毒的现象.     

双吡啶盐及其聚合物的研究Ⅱ.4,4’-(-1,4-苯撑-)-双-[N-烷(芳)基-2,6-二苯基]-吡啶盐及其聚合物对某些芳香酮还原反应的催化作用

在4,4’-(1,4-苯撑)-双-IN-烷(芳)基-2,6-二苯基I吡啶盐及其聚合物的催化下,二苯甲酮和苯乙烯基苯甲酮与中性条件下的锌粉发生双分子还原反应,生成相应的邻二叔醇;而结构类似的环状酮却主要发生单分子还原反应.双吡啶盐及其聚合物的结构和反应介质的极性对还原反应的速度有很大影响。本文对催化反应的机理也进行了讨论。     

α,β-不饱和酮中C＝C双键的Ir催化的高对映选择性氢化

α-手性酮化合物是一类重要的合成中间体. 至今已有很多工作致力于在酮羰基α-位构建手性中心, 但由于产物易于消旋, 有效地不对称催化合成α-手性酮化合物的方法非常有限. 从结构看通过α,β-不饱和酮的还原是一个构建酮羰基α-位手性中心的直接方法, 但α,β-不饱和酮的还原往往是羰基而不是双键被还原. 中国科学院上海有机化学研究所侯雪龙小组发现, 利用Phosphinooxazoline (PHOX)为配体的Ir催化剂1能有效地催化氢化α,β-不饱和酮的碳碳双键, 反应可以在常压下进行, 产物ee值均大于97%. 这一方法提供了一个高效、简便的α-手性酮化合物的合成手段[在此论文寄至Angew. Chem.编辑部前一星期, 德国的Bolm, C.也投寄了相似工作: Angew. Chem. Int. Ed. 2008, 47, 8920].     

甾体不对称合成的研究 Ⅸ.直链1,5-羟酮化合物经由氧化铝引起的手性转移

周维善等曾报道从微生物不对称还原所得(+)-(1S,2R)-单环1,5-羟酮化合物1的苯溶液,用氧化铝柱层析纯化得到了另一个(+)-(3’R)-单环1,5-羟酮化合物2.它们仅在羟基和酮基的位置不同,可能是由于与Al_2O_3形成六员环过渡态(A)而发生分子内的负氢离子转移,即分子内的氧化还原啪,从而引起了手性转移.因为羟酮处于1,5-位置,故也可称其为1,5-手性转移.以后我们又用与1结构类似的单环1,5-羟酮化合物3,也得到相同的结     

(+)-(1S,7aS)-1-羟基-7a-甲基-茚满-4-烯-5-酮的合成及其烷基化反应研究

以2-甲基-2-(3-丁酮)环戊烷-1,3-二酮为原料,经环合和还原反应合成了手性(+)-(1S,7aS)-1-羟基-7a-甲基-茚满-4-烯-5-酮(3);3在其羟基未进行保护情况下与不同芳香侧链进行α,β-不饱和酮的α-位烷基化反应,制备了5个3的衍生物,其结构经1H NMR确证。     

光学活性N-肉桂酰R(S)-4-异丙基四氢噻唑-2-硫酮的合成及其 量子化学的研究

用KBH~4,CaCl~2为还原使D及L缬氨酸甲酯还原得到光学活性产物R-3-甲基-2-氨基丁醇(2a)及S-3-甲基-2-氨基丁醇(2b)。2a,2b同CS~2在KOH存在下反应得到(R)-4-异丙基四氢噻唑-2-硫酮(3a)及(S)-4-异丙基四氢噻唑-2-硫酮(3b)。肉桂酰氯分别同3a及3b在Et~3N存在下反应得到N-肉桂酰(R)-4-异丙基四氢噻唑-2-硫酮(4a)及N-肉桂酰(S)-4-异丙基四氢噻唑-2-硫酮(4b)。用半经验的量子化学PM3方法研究了反应物和产物的电子结构,得到了产物的最优构型和电荷键序分布以及反应焓变。     

Studies on pyrazines. 7. The synthesis of 5-chloropyrazinecarboxylic acid

The titled carboxylic acid ( 1 ) was prepared by condensation of 2-furylglyoxal with aminoacetamide followed by chlorination of the resulting 2-hydroxy-5-(2′-furyl)pyrazine ( 2 ) and permanganate oxidation. The acid was further converted into methyl ester and 5-hydroxypyrazinecarboxylic acid.     

Furopyridines. I. Synthesis of furo[2,3-c]pyridine

The parent framework of furo[2,3-c]pyridine has been synthesized. 3-Furoic acid chloride ( 2 ) was reduced with bis(triphenylphosphine) copper(1) tetrahydroborate to afford 3-furaldehyde ( 3 ) which was condensed with malonic acid to give β-(3-furyl)acrylic acid ( 4 ). The acrylic acid 4 was converted to the acid azide ( 5 ), which in turn was cyclized to give furo[2,3-c]pyridin-7(6H)-one ( 6 ) by heating at 180° in diphenylmethane. The pyridone 6 was chlorinated with phosphorus oxychloride, followed by reduction with zinc and acetic acid to give furo[2,3-c]pyridine ( 8 ).     

Contribution to the analysis of the essential oil of Helichrysum italicum (Roth) G. Don. Determination of ester bonded acids and phenols

The essential oil of Helichrysum italicum (Roth) G. Don (everlasting or Immortelle essential oil) was isolated by hydrodistillation and analysed by GC and GCMS. Forty four compounds were identified. The main components were alpha-pinene(12.8%), 2-methyl-cyclohexyl pentanoate (11.1 %), neryl acetate (10.4%), 1,7-di-epi-alpha-cedrene (6.8%) and other compounds. The oil was fractionated and ester-containing fraction was hydrolysed with KOH/H(2)SO(4). The liberated volatiles were analysed by GC and GC-MS: three phenols and twenty seven volatile carboxylic acids were identified[70% low fatty acids (C(2)-C(5)), 15% C(10)-C(12) acids and 15% other acids]. The main acids were acetic acid (24.3%) propanoic acid (17.2%), 2-methylpropanoic acid (11.4%),dodecanoic acid (8.7%), 2-methylbutanoic acid (8.3%), (Z)-2-methylbutenoic acid(5.1%) and decanoic acid (4.6%). With respect to the identified bonded carboxylic acids,the minimal number of esters in the oil was twenty seven, but their overall quantity was probably larger due to different possible combinations of alcohols with acids to form esters. On the other hand, only six main esters were identified in the oil before fractionation and hydrolysis.     

Lupane triterpenoids,antioxidant potential and antimicrobial activity of Myrciaria floribunda (H. West ex Willd.) O. Berg.

Chemical composition of the methanol extract of Myrciaria floribunda leaves was investigated. The nor-lupane triterpenoids platanic acid and messagenic I acid were identified, along with other known triterpenoids (betulinic aldehyde, ursolic acid acetate and betulinic acid), a new lupane triterpenoid (2α,6α,30-trihydroxybetulinic acid) and the flavonoids catechin, quercetrin and mirycitrin. The structures were determined by spectroscopic methods (NMR, LC-MS, GC-MS). The major isolated compound was betulinic acid. The methanol extract and 2α,6α,30-trihydroxybetulinic acid were evaluated for their DPPH scavenging potential. The tested triterpenoid was one hundred times more active than betulinic acid, but less active than the extract. Screening for antimicrobial activity showed that the methanol extract was active against Staphylococcus aureus and Escherichia coli, but inactive against Candida albicans and Candida krusei, while 2α,6α,30-trihydroxybetulinic acid was inactive to all tested microorganisms.     

Folic acid analogs. Modifications in the benzene-ring region. 5. 2′,6′-diazafolic acid

The synthesis of 2′,6′-diazafolic acid was accomplished by the condensation of 2-acetylamino-4(3H)pteridinone-6-earboxaldehyde (XIV) with diethyl N-[(5-amino-2-pyrimidinyl)carbonyl]-L-glutamate (XIII) followed by reduction of the anil double bond and alkaline hydrolylic cleavage of the N²-acetyl and ethyl ester protecting groups. Intermediate XIII was prepared by starling with 5-nitro-2-styrylpyrimidine (VI) and proceeding via 5-arnino-2-styrylpyrimidine (IX). The henzyloxycarbonyl derivative of IX was prepared and oxidized to the corresponding 5-benzyloxycarbonylaminopyrimidine-2-carboxylic acid (XI). The coupling of XI with diethyl L-glutamate followed by hydrogenolysis of the henzyloxycarbonyl function afforded the desired intermediate XIII. 2′,6′-Diazafolic acid was a potent inhibitor of Streptococcus faecium and displayed marginal activity against leukemia 1,1210 in mice.     

Research on steroids. 41. Conversion products of 17-alpha-strophanthidins

Pseudostrophanthidin ( 2 ) can be easily prepared by treating strophanthidin ( 1 ) with concentrated hydrochloric acid in the cold [1]. 2 has served as the initial product for the preparation of a number of analogues and homologues of steroid hormones [2] [3]. 17α-Pseudostrophanthidin ( 4 ) is considered a suitable starting material for an extension of these investigations. It was logical to attempt the preparation of 4 from 17α-strophanthidin ( 3 ) under conditions identical with those used in the conversion of 1 into 2. However, these experiments did not lead to 4 but, instead, by way of the unstable 14ξ-chloro-14-deoxy-17α-strophanthidin ( 5 ) to 14-anhydro-17α-strophanthidin ( 6 ). This result is essentially in agreement with findings reported in the literature [5]. To support the structure assigned to 6 , this compound was also prepared by a different, unambiguous, route. Treatment of 3 with thionyl chloride in pyridine gave mainly 3β, 5β-O, Osulfinyl-14-anhydro-17α-strophanthidin ( 8 ), which was converted into 6 by mild hydrolysis. In turn 6 , as obtained via the unstable chloro compound 5 , gave on treatment with thionyl chloride in pyridine a product identical with 8. – 6 was characterized as the 3-acetate 7 . As extension of these experiments, 17α-strophanthidol ( 10 ) [6] was treated with concentrated hydrochloric acid in the cold under conditions similar to those used in the conversion of 3 into 6 by way of 5. This led to the isolation of 14-anhydro-17α-strophanthidol ( 11 ), which could also be obtained by the reduction of 6 with aluminium amalgam. As is known [1] [8], strophanthidinic acid ( 13 ) can be converted into strophanthidinic acid 19,8-lactone ( 14 ) by treatment with concentrated hydrochloric acid in the cold. In view of the negative results obtained in the attempt to transform 3 into 4 under these conditions, the question arose as to whether the conversion of 17α-strophanthidinic acid ( 15 ) into 17α-strophanthidinic acid 19,8-lactone ( 16 ) by the same procedure is also impossible. 15 was prepared by treating 3 with hydrogen peroxide and was characterized as the methyl ester 17 and the methyl ester of the 3-benzoate ( 18 ). 15 and 17 have been mentioned in the literature [5], but the physical constants reported differ from those obtained in this laboratory. It was demonstrated that after treating 15 with concentrated hydrochloric acid in the cold, no 16 could be isolated but, instead, an unstable chloro compound 19 which was converted into 14-anhydro-17α-strophanthidinic acid ( 20 ). 20 was characterized as the methyl ester 21 and the 3-acetate 22 .     

Biosynthesis of cytochalasans. Part 6. The mode of incorporation of phenylalanine into cytochalasin D1.

Rapid equilibrium of D - and L -phenylalanines with phenylpyruvic acid ( 4 ) was shown to account for their equally efficient incorporation into cytochalasin D ( 1 ) by Zygosporium masonii. Transamination of phenylalanines stereospecifically labelled with tritium at C(2) and C(3) proceeded with complete hydrogen loss at the α position and extensive loss at the β position. Considerable suppression of the incorporation of the D -amino acid by phenylpyruvic acid ( 4 ) indicated that the L -enantiomer is the primary precursor of 1 .     

Reactions on polymers with amine groups. V. Addition of pyridine and imidazole groups with acetylenecarboxylic acids

Unsaturated macromolecular carboxybetaines were obtained by reaction of poly(4-vinylpyridine) and poly(N-vinylimidazole) with propiolic acid. A kinetic model was presented for 4-methylpyridine. It consists of three coupled reactions: neutralization, addition which involves two molecules of acid and leads to a cation–anion pair structure, where the cation results from the addition of the amine nitrogen to the triple bond of acid, and an equilibrium reaction between the ion-pair structure and the betaine structure. The addition rate was found to be higher for poly(4-vinylpyridine) than for poly(N-vinylimidazole); it was also higher in water than in a water–methanol mixture. The reaction with acetylenedicarboxylic acid was carried out on poly(N-vinylimidazole), but the transformed units showed the structure that results from propiolic acid. The betaine products from 4-methylpyridine did not polymerize by radical initiation. The polymeric products show characteristics of photocrosslinking polymers. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1615–1623, 1998     

Seimatoric acid and colletonoic acid:Two new compounds from the endophytic fungi,Seimatosporium sp.and Colletotrichum sp.

A new metabolite,named seimatoric acid(1),representing a new oxobutanoic acid derivative has been isolated from Seimatosporium sp., in addition to four known compounds viz.,2-hydroxymethyl-4β,5α,6β-trihydroxycyclohex-2-enone(2),(-)-phyllostine(3),(+)-epiepoxydon(4) and(+)-epoxydon monoacetate(5).Similarly one new benzoic acid derivative,named colletonoic acid(6) was isolated from the ethyl acetate fraction of Colletotrichum sp.The structures of the new compounds were elucidated by detailed ~1 H NMR,~(13)C NMR,COSY,HMQC.HMBC spectroscopic analysis,and HR-E1-MS.Seimatoric acid(1)was also isolated from another taxonomical unidentified fungal strain 4295 in ourgroup.The structures of the known compounds were elucidated by their spectral data comparison to literature data.Preliminary studies showed that colletonoic acid(6) showed good antibacterial,antifungal,and antialgal activities.     

Allan J. Bard and Cynthia G. Zoski (Eds): Electroanalytical Chemistry

Coupled with evaporative light scattering detection, a high-speed counter-current chromatography (HSCCC) method was applied to the separation and purification of three tauro-conjugated cholic acids of taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and taurohyocholic acid (THCA) from Pulvis Fellis Suis (Pig gallbladder bile) for the first time. The two-phase solvent system composed of chloroform-methanol-water-acetic acid (4:4:2:0.3, v/v/v/v) was selected for the one-step separation where the lower phase was used as the mobile phase in the head to tail elution mode. The revolution speed of the separation column, flow rate of the mobile phase and separation temperature were 800 rpm, 1.5 ml/min and 25°C respectively. From 100 mg of the crude extract, 10.2 mg of TCDCA, 11.8 mg of THDCA and 5.3 mg of THCA were obtained with the purity of 94.6%, 96.5% and 95.4%, respectively. in one step separation The HSCCC fractions were analyzed by high-performance liquid chromatography (HPLC) and the structures of the three tauro-conjugated cholic acids were identified by ESI-MS, (1)H NMR and (13)C NMR.