Chemical Synthesis of Amino Acid Containing Lipids I: Lipids Derived from Monobasic Amino Acids

Long-chain alkyl esters of N-acyl monobasic amino acids were prepared by reacting N-acyl amino acids with long-chain alkyl methane sulfonates in the presence of sodium bicarbonate in dimethylformamide. The necessary N-acyl amino acids were prepared by reacting an amino acid with an active fatty acid ester of p-nitrophenol in ethanol containing sodium bicarbonate. Reaction between a fatty acid and p-nitrophenol in chloroform, in presence of thionyl chloride, yielded the active ester necessary for the N-acylation of an amino acid.     

Geschützte Aminooxazoline der Arabinose und Ribose

Protected Aminooxazolines of Arabinose and Ribose The reaction of D-arabinose or D-ribose with cyanamide afforded 2-amino-1,2-oxazolines 1 which were treated with dihydropyran or ethylvinylether. In the presence of PTS the 3′,5′-di-THP- or 3′,5′-di-O-ethoxyethyl-D-arabino-(ribo)-furo-[1′,2′:4,5]-2-oxazolines 2 and 3 could be isolated as useful intermediates for the preparation of nucleosides. When the 2-aminooxazolines are treated with benzyloxycarbonylchloride or its p-substituted derivatives the N-3 atom of the oxazoline ring is preferentially substituted. Under these conditions the exocyclic amino function is always replaced and 2-oxo-3-benzyloxycarbonylderivatives 4 are obtained; only traces of the corresponding 2-aminoderivatives 5 are formed. Treatment of 4 with acetic anhydride, benzoylchloride, and benzoylcyanide, respectively, results in the 3′-, 5′-di-O-acyl derivatives 6 . Mild hydrolysis of the benzyloxycarbonyl group with trifluoroacetic acid yields the 3′,5′-di-O-acyl-D-arabino-(ribo)-furo-[1′,2′:4,5]-2-oxooxazolidines as further intermediates for the synthesis of nucleosides.     

硝唑尼特合成工艺的研究

由乙酰水杨酸和2-氨基-5-硝基噻唑为原料,选用N,N-二甲基甲酰胺和三乙胺分别作为催化剂和缚酸剂,经酰胺化反应生成一种抗寄生虫新药—硝唑尼特,其较佳的工艺条件:酰氯化反应温度70℃,氯化亚砜与乙酰水杨酸的摩尔比为1.3∶1,乙酰水杨酸与2-氨基-5-硝基噻唑的摩尔比为1.4∶1,酰胺化反应时间2.5 h,收率达76.8%。该工艺简单,收率高,具有较好的应用价值。     

Characterization and Toxicity of Amanita cokeri Extract

The nonprotein amino acids 2-amino-3-cyclopropylbutanoic acid and 2-amino-5-chloro-4-pentenoic acid were isolated from the mushroom Amanita cokeri. The cyclopropyl amino acid is toxic to the fungus Cercospora kikuchii, the arthropod Oncopeltus fasciatus (milk weed bug), and the bacteria Agrobacterium tumefaciens, Erwinia amylovora, and Xanthomonas campestris. Toxicity to bacteria was reversible by addition of isoleucine to the medium. No toxicity was observed for 2-amino-5-chloro-4-pentenoic acid.     

油酸酰胺的选择性加氢工艺研究

研究首次提出油酸酰胺直接选择性加氢工艺,选用价格低廉的骨架镍催化剂对油酸酰胺进行了选择性加氢,取得了较好的效果。实验结果表明,通过选择性加氢工艺,其中的亚油酸酰胺、亚麻酸酰胺等不饱和组分大部分转化为油酸酰胺而被除去,油酸酰胺含量由67.532%增加到76.198%,提高了油酸酰胺的含量和使用性能。得出反应条件为：反应温度160℃,反应压力405.3 kPa,反应时间3.0 h,催化剂加量3%。     

Continuous spectrophotometric assay of conjugated bile acid hydrolase

Conjugated bile acid hydrolase (CBAH) refers to a class of enzymes which catalyze the cleavage of the amino acid moieties from conjugated bile acids. These enzymes are significant because of their role in providing substrates for further microbial metabolism in the gastrointestinal tract. They also are used in research laboratories for the deconjugation of bile acids prior to structural analyses. A continuous spectrophotometric assay for CBAH activity was developed using a conjugate of cholic acid and the chromophore, 5-amino-2-nitro-benzoic acid. The free chromophore is detected by virtue of its absorbance at 410 nm. The CBAH fromClostridium perfringens displayed aK _m for this substrate of 120 μM. These results demonstrate that this new compound functions as an effective substrate of the enzyme and forms the basis for a convenient and rapid method to monitor CBAH activity.     

An investigation of alumina-supported catalysts for the selective catalytic oxidation of ammonia in biomass gasification

Alumina-supported catalysts containing different transition metals (Ni, Cu, Cr, Mn, Fe and Co) were prepared and tested for their activity in the selective oxidation of ammonia reaction at high temperatures (between 700 and 900 °C) using a synthetic gasification gas mixture. The catalysts were also characterised for their acidic properties by infrared studies of pyridine and ammonia adsorption and reaction/desorption. The Ni/Al₂O₃ and Cr/Al₂O₃ catalyst displayed the highest selective catalytic oxidation (SCO) activity in that temperature range with excellent N₂ selectivities. FT-IR studies of adsorbed pyridine and NH₃ indicate that Lewis acid sites dominate and that NH₃ adsorption on these sites is likely to be the first step in the SCO reaction. FT-IR studies on less active catalysts, particularly on Cu/Al₂O₃ allowed the detection of oxidation intermediates, amide (NH₂), and possibly hydrazine and imido and nitroxyl species. The amide and hydrazine intermediate gives credence to a proposed SCO mechanism involving a hydrazine intermediate, while the proposed imide, =N–H, and/or nitroxyl, HNO species could be intermediates in incomplete oxidation of NH₃ to N₂O.     

治疗骨髓增殖性肿瘤药物TG101209的合成

本文研究了治疗骨髓增殖性肿瘤药物TG101209的合成工艺。以2,4-二羟基-5-甲基嘧啶为起始原料,与三氯氧磷、氨水发生氯化、取代反应生成2-氯-4-氨基-5-甲基嘧啶(B),B再与N-叔丁基-3-溴苯磺酰胺(C)发生Buchwald偶联反应得到3-[(2-氯-5-甲基-4-嘧啶基)胺基]-N-(叔丁基)苯磺酰胺(D)。以甲醇为溶剂,D与CH3OH-HCl反应得到3-[(2-氯-5-甲基-4-嘧啶基)胺基]-N-(叔丁基)苯磺酰胺盐酸盐(E),E与1-甲基-4-(4-氨基苯基)哌啶(G)发生亲核取代反应得到N-叔丁基-3-(5-甲基-2-[4-(4-甲基-1-哌嗪)苯胺基]-4-胺基嘧啶)-苯磺酰胺(TG101209)。总收率达到30.9%,HPLC测得纯度达到99.7%。     

Synthesis of N-acyl amino acids and correlation of structure with surfactant properties of their sodium salts

The effect of structural variation in fatty acid and amino acid moieties on surfactant properties of sodium salts of N-acyl condensates of amino acids was investigated. Pure N-acyl leucines and N-lauroyl condensates of different amino acids were synthesized and neutralized. Among the N-acyl leucinates, N-lauroyl leucinate exhibited optimum properties and compared well with sodium lauryl sulfate (SLS). Among the salts of Nα-lauroyl amino acids, Nα-lauroyl lysinate was found comparable to SLS. Salts of Nα-lauroyl condensates of leucine, tryptophan, phenylalanine and proline showed good wetting ability; proline also displayed high calcium ion tolerance. Salts of N-lauroyl tyrosine and phenylalanine exhibited good foaming ability. N-Lauroyl aspartate showed inferior properties compared to SLS in spite of having an additional carboxylic group. HCT Communication No. 2525.     

氟丙嘧草酯的合成与生物活性

氟丙嘧草酯是先正达公司开发的非选择性脲嘧啶类除草剂,2001年上市。以5-氨基-2-氯苯甲酸为起始原料,经酰氯化并与2-羟基异丁酸烯丙酯的钠盐发生酯化反应,得到5-氨基-2-氯苯甲酸(1-甲基-1-烯丙氧羰基乙)酯(M-3);该中间体与3-(3,3-二甲基脲基)-4,4,4-三氟巴豆酸乙酯进行环合后,进一步经N-甲基化反应得到目标产物。目标化合物和部分中间体的结构经1H NMR和LC-MS确证。苗后除草活性测试结果表明,氟丙嘧草酯对百日草和苘麻具有优异的除草活性,在9.4 g/hm~2有效成分用量下对二者的防除效果分别为100%和65%。     

Neue Pyoverdin-Siderophore aus Pseudomonas putida C

New Pyoverdin Siderophores from Pseudomonas putida C Four new pyoverdins (C 2A, C 2B, C 3A, C 3B) were isolated from cultures of Pseudomonas putida C. Their structures were elucidated by chemical and spectroscopic methods. The compounds consist of a chromophore – (1S)-5-amino-2,3-dihydro-8,9-dihydroxy-1H-pyrimido [1,2-a]quinoline-1-carboxylic acid – substituted at the amino group with a dicarboxylic acid or its amide. The carboxyl group of the chromophore is amidically bound to the N-terminus of L-Asp-D-[N⁵-hydroxy-N⁵-(D-β-hydroxybutyryl)] Orn-D-Dab-L-Thr-Gly-D-Ser-L-Ser-L-threo-β-hydroxy-Asp-L-Thr. The four pyoverdins differ only in the nature of the dicarboxylic acid (amide), viz. L-malamoyl- (C 2A), succinamoyl- (C 2B), L-3-carboxy-2-hydroxypropanoyl- (C 3A) or 3-carboxypropanoyl (C 3B) residue. The hydroxamate function consists of N⁵-hydroxy-Orn and β-hydroxybutyric acid, a structural unit which has been encountered for the first time in a pyoverdin.     

Histone Tail Sequences Balance Their Role in Genetic Regulation and the Need To Protect DNA against Destruction in Nucleosome Core Particles Containing Abasic Sites

Abasic sites (AP) are produced 10 000 times per day in a single cell. Strand cleavage at AP is accelerated ≈100-fold within a nucleosome core particle (NCP) compared to free DNA. The lysine-rich N-terminal tails of histone proteins catalyze single-strand breaks through a mechanism used by base-excision-repair enzymes, despite the general dearth of glutamic acid, aspartic acid, and histidine—the amino acids that are typically responsible for deprotonation of Schiff base intermediates. Incorporating glutamic acid, aspartic acid, or histidine proximal to lysine residues in histone N-terminal tails increases AP reactivity as much as sixfold. The rate acceleration is due to more facile DNA cleavage of Schiff-base intermediates. These observations raise the possibility that histone proteins could have evolved to minimize the presence of histidine, glutamic acid, and aspartic acid in their lysine-rich N-terminal tails to guard against enhancing the toxic effects of DNA damage.     

脂肪酸系列表面活性剂的研究进展

概括和综述了4大类10余个脂肪酸系列表面活性剂的合成、性能和应用现状，重点评述了烷醇酰胺及其衍生物、乙氧基化脂肪酸甲酯、脂肪酸甲酯磺酸盐、N-酰基ED3A、氨基酸、咪唑啉、甜菜碱、双子表面活性剂等脂肪酸系列表面活性剂的研究进展。此系列表面活性剂易生物降解、安全、多功能和高效能。     

Formation of N- and O-methyl derivatives of lipids containing amino,amide or hydroxy groups by the pyrolytic reaction with trimethylsulfonium hydroxide

Base-catalyzed transesterification of acyl lipids with methanol in the presence of trimethylsulfonium hydroxide (TMSH) is an easy and convenient method for the preparation of fatty acid methyl esters for GC analyses. However, lipids containing functional groups such as amino, amide and hydroxy groups are converted in varying degrees to the corresponding N- and O-methyl derivatives by the pyrolytic reaction of TMSH occurring in the injector of the gas chromatograph. For example, lipids containing amino or amide groups are converted into the corresponding N-methyl and N,N-dimethyl derivatives, fatty acid ethanolamides to the corresponding N-methyl, O-methyl and N,O-dimethyl derivatives, whereas alkyl methyl ethers are formed from long-chain alcohols. Furthermore, 2-O- and 3-O-monomethyl ethers as well as 2,3-di-O-methyl ethers are formed from 1-O-alkylglycerols, methoxy fatty acid methyl esters from hydroxy fatty acids as well as steryl 3β-O-methyl ethers from cholesterol and other sterols. Since some of the mentioned artefacts may interfere with fatty acid methyl esters in GC separations the TMSH derivatization method is recommended only with caution for lipids containing amino, amide and hydroxy groups. The methylation reactions, which finally lead to the corresponding N-methyl, O-methyl, N,N-dimethyl or N,O-dimethyl derivatives of fatty acids and lipids may, however, be of some diagnostic value for the structural analysis of such lipids by GC/MS.     

神经降压素的固相合成工艺研究

神经降压素是由13个氨基酸残基组成的生物活性多肽,具有多重生理功能,且高活性、作用快速,可作为潜在的安定药、镇痛药和降压药等,具有广阔的应用前景。本研究主要进行了神经降压素固相合成的工艺研究。以Fmoc保护的氨基酸为原料,Wang树脂为载体,按照神经降压素的氨基酸序列,从C端向N端进行合成。考察了缩合试剂、脱保护试剂、脱出树脂等条件对合成效果的影响,确定了合成工艺:以二氯甲烷(DCM)为反应溶剂,O-苯并三氮唑-N,N,N′,N′-四甲基脲四氟硼酸酯(TBTU)/1-羟基苯并三氮唑(HOBT)/N,N-二异丙基乙胺(DIEA)为缩合体系,采用(三氟乙酸(TFA)/H2O/甲基苯基硫醚(thioanisole)/Phenol/乙二硫醇(EDT)体系,体积比为82∶5∶5∶6∶2的下树脂条件,2倍过量保护氨基酸进行缩合反应,反应时间为3h。反应结果使神经降压素粗品的收率达61.8%,纯度达46%。     

微波辅助法合成手性β-氨基酸

手性β-氨基酸是一类在药物开发和生物研究中具有广泛应用的中间体,尝试了以L-天冬氨酸为手性源合成手性β-氨基酸的研究,其合成方法：首先对天冬氨酸进行氨基保护,然后利用微波,高效地合成（ S）-N-保护的丝氨酸-γ-内酯,最后通过傅克反应,合成具有芳香性的手性β氨基酸。具有路线短、操作方便、绿色经济等优点,适合工业化大生产。     

Preparation and properties of poly(amide acid) gels

Poly(amide acid) gels were first synthesized by the reaction of a poly(amide acid) with diisocyanates as crosslinking agents. Poly(amide acid) was synthesized from 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) and bis(4-amino-3-ethylphenyl)methane (DEDPM). From the change in the IR spectra, the key process of crosslinking was determined to be the decarboxylation from the reaction product of the carboxyl group and isocyanate group. The gels markedly change their volume with the composition change of NMP–water mixed solvent. Thermal properties of the poly(amide acid) gels are also studied.     

Synthesis of novel hyperbranched poly(ester-amide)s based on acidic and basic amino acids via “AD + CBB′” couple-monomer approach

A series of novel hydroxyl- or methyl ester- terminated hyperbranched poly(ester-amide)s (HBPEAs) based on acidic (l-glumatic acid and l-aspartic acid) and basic amino acids (l-lysine) have been synthesized via the “AD + CBB′” couple-monomer approach. The ABB′ intermediates were stoichiometrically formed through thio-ene reaction benefited from reactivity differences between functional groups. Without any purification, in situ self-polycondensations of the intermediates at elevated temperature in the presence of Ti(OBu)₄, as a catalyst, afforded HBPEAs with high molecular weights. More rapid polymerization rate and much higher molecular weight as well as broader polydispersity were observed for the polymerization process of intermediates based on acidic amino acids than basic amino acids which is related to the catalytic mechanism and structure difference of intermediates. Moreover, polymerization of intermediate derived from l-aspartic acid was carried out faster by comparison with that from l-glumatic acid. The DB values were approximately estimated to be 47%–49% for the polymers derived from l-aspartic acid and l-glutamic acid. The resultant HBPEAs possessed glass transition temperature (T_g) in the range of ?3 to 11 °C, among which those derived from l-lysine shows the highest T_g, and decomposition temperatures at 10% weight loss under air and nitrogen are in close regions of 261–271 °C and 264–268 °C, respectively.     

氯虫苯甲酰胺的合成及表征

以3-甲基-2-硝基苯甲酸为原料通过RaneyNi加氢还原制得3-甲基-2-氨基苯甲酸,接着与N-氯代丁二酰亚胺(NCS)反应制得3-甲基-2-氨基-5-氯苯甲酸,然后3-甲基-2-氨基-5-氯苯甲酸与氯化亚砜在75～80℃下回流3h后,接着缓慢滴加甲胺水溶液,在室温下搅拌反应12h,得到2-氨基-5-氯-N,3-二甲基甲酰胺。然后再与3-溴-1-(3-氯吡啶-2-吡啶基)-1 H-吡唑-5-甲酸在-5～0℃下滴加甲基磺酰氯反应得到产品氯虫苯甲酰胺,四步总收率37.0%,产品HPLC纯度是96.05%。     

单氨基改性PBO的AB型新单体的合成

研究了以4-(甲氧羰基)-2-硝基苯甲酸(β-MNT)与4-氨基-6-硝基间苯二酚盐酸盐(ANR·HCl)为原料经酰氯化、N-酰化、环合、水解和催化加氢还原等一系列反应合成得到中间体4-((2,4-二羟基-5-硝基)氨甲酰基)-3-硝基苯甲酸甲酯(3-NMNC)、4-(5-硝基-6-羟基-2-苯并 唑基)-3-硝基苯甲酸甲酯(3-NMNB)、4-(5-硝基-6-羟基-2-苯并 唑基)-3-硝基苯甲酸(3-NNBA)及单氨基改性PBO的AB型新单体4-(5-氨基-6-羟基-2-苯并 唑基)-3-氨基苯甲酸(3-AABA),并对环合、水解和催化还原加氢的反应条件进行了优化.结果表明:对于环合反应,以二乙二醇二甲醚为溶剂,PPA为环合脱水剂其中P₂O₅含量84%,w(PPA):w(3-NMNC)=9.5:1,反应温度140℃,反应时间8h,3-NMNB收率73.16%,HPLC纯度99.10%;水解反应,以乙醇与水为溶剂,n(K₂CO₃):n(3-NMNB)= 1.8:1,加热水解2h,3-NNBA收率74.19%,HPLC纯度为98.59%;催化加氢还原反应,甲醇为溶剂,w(10%Pd/C):w(3-NNBA)=1:20,1 MPa氢压,80℃反应5h得3-AABA,HPLC纯度99.43%,收率65.08%.中间体和产物结构经FT-IR、¹³C-NMR和ESI-MS表征确认.