Synthesis of tricyclic analogues of methyllycaconitine using ring closing metathesis to append a B ring to an AE azabicyclic fragment

The synthesis of several ABE tricyclic analogues of the alkaloid methyllycaconitine 1 is reported. The analogues contain two key pharmacophores: a homocholine motif formed from a tertiary N-ethyl amine in a 3-azabicyclo[3.3.1]nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester 4. The synthesis of the ABE tricyclic analogues of MLA 1 began with selective allylation at C-3 of 3 to produce allyl beta-keto ester 4. Double Mannich reaction of 4 with ethylamine and formaldehyde produced bicyclic amine 5 The C-9 ketone of bicyclic amine 5 was selectively reduced to form bicyclic alcohols 6 and 7 which were subsequently allylated to form dienes 8 and 9. Ring closing metathesis of dienes 8 and 9 afforded tricyclic ethers 11 and 12, respectively, the C-8 ester of which was reduced to a hydroxymethyl group to form ABE tricyclic analogues 13 and 14. Addition of allylmagnesium bromide to the C-9 ketone of 20 afforded dienes 21 and 22, which underwent ring closing metathesis to form tricyclic esters 23 and 24, respectively. Reduction of the C-8 ethyl ester of 23 and 24 to a hydroxymethyl group afforded diols 25 and 26 respectively. The 2-(3-methyl-2,5-dioxopyrrolin-1-ly)benzoate ester was introduced by conversion of alcohols 13, 14, 25 and 26, to the anthranilate esters 16, 17, 27 and 28 using N-(trifluoroacetyl)anthranilic acid 15 followed by fusion with methylsuccinic anhydride to afford the substituted anthranilates 18, 19, 29 and 30 containing the key 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester pharmacophore.     

Tributylstibine-mediated olefination of carbonyl compounds with bromomalonic ester and with dibromomalonic ester—A possible pathway through a stibonium ylide via halophilic initiation by tertiary stibines

Tributylstibine can mediate the olefination of carbonyl compounds with bromomalonic ester and with dibromomalonic ester. An initial halophilic attack of tributylstibine on the bromine of bromomalonic or dibromomalonic ester forming an ion pair of bromotributylstibonium cation and malonic (A) or bromomalonic ester carbanion (B) , respectively, is proposed. These ion pairs react with carbonyl compounds to achieve subsequent olefination. Alternatively, 2 equiv of A collapse, with elimination of malonic ester, to form stiborane D , and the ion pair B reacts with another equivalent of tributylstibine to form stiborane D. This last undergoes a Wittig-type reaction with carbonyl compound to achieve olefination.     

Capillary electrophoresis chemiluminescent detection system equipped with a two-step postcolumn flow interface for detection of some enkephalin-related peptides labeled with acridinium ester

Despite its low equipment cost and simple design, as one of the sensitive detectors for CE, the chemiluminescence (CL) detector was less developed compared to the detectors of MS and LIF. The main reasons were the limitation of CL reagents, the repeatability problems and the relatively low sensitivity compared to LIF. In this paper, a highly sensitive CE-CL detection system was developed for detection of some enkephalin-related peptides labeled with acridinium ester. A new detection interface was designed for CE with CL detection of acridinium ester and its labeled analytes. The interface included two sections: one was used to acidify the capillary outflow so that the corresponding acridinium pseudo-base form can be changed into acridinium ester form by adding excess acid to the system; the other was designed to provide a suitable solution to produce the CL from acridinium ester. The effect factors, such as pH, the concentration of reaction reagents and the flow rates of the reagents, were investigated. The results showed that acridinium ester had similar CL properties in this interface when pH values of CE BGE were changed from 2.0 to 10.8. The interface was used to detect acridinium ester and three acridinium ester-labeled enkephalin-related peptides, the corresponding LODs were found to be in the attomole range. This CL detection system proved to be of high sensitivity, good repeatability, and relatively low cost.     

Die Glykoside der Wurzeln von Kanahia laniflora (FORSSK.) R. BR. 1. Mitteilung: Isolierungen. Glykoside und Aglykone, 299. Mitteilung

The roots of Kanahia laniflora (FORSSK .) R. BR . contain, in addition to small quantities of cardenolides, a large amount of ester glycosides which are difficulty separable from one another. However, two of these ester glycosides were obtained in a nearly pure form. The crude mixture of ester glycosides, after mild acidic hydrolysis, gave a mixture of acyl-genins and three sugars: D -oleandrose, D -digitoxose and D-canarose, all of which were obtained in crystalline form. Acetic acid, benzoic acid and another unidentified acid were obtained on alkaline hydrolysis of the mixture of acyl-genins along with 17-isolineolon, lineolon, deacetylmetaplexigenin and a small amount of sarcostin-ketone. Besides these known genins, three probably new genins (α, τ, λ) were obtained in small, but crystalline amounts.     

Enantiodivergent, biocatalytic routes to both taxol side chain antipodes

[Reaction: see text]. Two enantiocomplementary bakers' yeast enzymes reduced an alpha-chloro-beta-keto ester to yield precursors for both enantiomers of the N-benzoyl phenylisoserine Taxol side chain. After base-mediated ring closure of the chlorohydrin enantiomers, the epoxides were converted directly to the oxazoline form of the target molecules using a Ritter reaction with benzonitrile. These were hydrolyzed to the ethyl ester form of the Taxol side chain enantiomers under acidic conditions. This brief and atom-efficient route to both target enantiomers demonstrates both the synthetic utility of individual yeast reductases and the power of genomic strategies in making these catalysts available.     

大环手性磷酰胺对氨基酸衍生物的分子识别研究

以(S)-α-甲基苯乙胺和天然氨基酸(L-丙氨酸、L-苯甘氨酸及L-苯丙氨酸)为手性源,以2,5-二(邻羟基苯基)-1,3,4- 二唑和2,4-二(邻羟基苯基)-1,3,5- 二唑为刚性单元,合成了一系列具有光学活性的新型含 二唑磷酰胺和磷酯手性大环化合物.用NMR,IR和FABMS方法研究了所合成的手性大环对氨基酸甲酯盐酸盐和二肽的分子间相互作用和分子识别.结果表明,这些主体对D-或L-氨基酸甲酯盐酸盐和二肽具有选择性的结合作用.     

Synthesis of potential antitumor agents,dimeric and trimeric chlorins,from methylpheophorbide <Emphasis Type="Italic">a</Emphasis>

A series of dimeric and trimeric chlorins were synthesized from methylpheophorbide a. They are potential photosensitizers for photodynamic therapy in oncology. The macrocycles were conjugated due to the formation of ester and amide bonds. The carboxy groups were activated and catalytic transesterification was carried out to form the ester bond. The amide bond was formed using carboxy group activation; in several cases, amidation of the ester group in position 13(2) of the exocycle of methylpheophorbide α was carried out, which does not require activation.     

Breakdown of Chlorophyll: Partial synthesis of a putative intermediary catabolite. Preliminary communication

The partial synthesis of 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a ( 1 ) from pheophorbide a methyl ester (2) is described. A regioselective, photooxygenolytic reaction of (pheophorbidato a methyl ester)cadmium(II)( 3 ) provides the entry to the crucial 4,5-secoporphinoid structure in form of the (10,22-dihydro-4,5-dioxo-4,5-seco-pheophorbidato a methyl ester)cadmium(II) ( 4 ). The hydride reduction of this 4,5-dioxo-4,5-secophytoporphyrin ester occurs selectively at the ‘eastern’ meso-position to lead (after demetallation) to 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a methyl ester ( 5 ). This oxobilin-carbaldehyde has the structure assigned earlier to an ester of an isolation form of the red pigment(s) from Chlorella protothecoides. Hydrolysis of the propanoate ester function of 5, selectively catalyzed by pig liver esterase, then yields the title compound 1 . The red tetrapyrrole 1 may represent an intermediary chlorophyll catabolite in degreening plants.     

关于双环[2.2.1]庚-5-烯-2,3-二甲酰亚胺

对以NA封头的“PMR型”聚酰亚胺溶液中产生的沉淀物进行了分离和鉴定。测定了NA乙酯、二苯甲酮四甲酸二乙酯与二氨基二苯甲烷的反应速度常数,并对树脂溶液的稳定性和低聚物的结构进行了讨论。     

3,8-双乙酰基次卟啉二甲酯的合成

以氯化血红素(Ⅰ)为原料,经过溴化氢-冰醋酸加成反应、羟基亲核取代反应和无水氯化氢催化酯化反应制得3,8-双-(1-羟基乙基)次卟啉二甲酯(Ⅲ),然后通过琼斯试剂氧化反应制备了3,8-双乙酰基次卟啉二甲酯(Ⅳ)。 考察了血红素与溴化氢-冰醋酸饱和溶液反应过程中温度和时间对3,8-双-(1-羟基乙基)次卟啉二甲酯(Ⅲ)产率的影响;改进了酯化反应的实验条件;选用了廉价易得、选择性较好的羟基选择性氧化剂。 实验结果表明,当反应温度为35 ℃、反应时间为25 h时,血卟啉(Ⅱ)的产率最高,为98.5%;当催化剂为无水氯化氢时产物(Ⅲ)的产率最高,为72.1%;使用琼斯试剂做氧化剂使实验成本大大降低。 通过1H NMR、MS和IR测试技术对产物结构进行了表征。     

Totalsynthese von Betalainen

A total synthesis of betalaine pigments ( 6 ) is described. The key intermediate is betalamic acid in the form of its dimethyl ester semicarbazone ( 9 ), which was transformed with L-proline ( 16 ) into indicaxanthine dimenthl ester ( 5 ), with L-cyclodopa methul ester ( 17 ) into betanidine trimethyl ester ( 3 ) and by hydrolysis of the latter into betanidine ( 2 ).     

Investigations on the cure chemistry and polymer properties of benzoxazine-cyanate ester blends

Thermosetting polymer blends composed of bisphenol A based benzoxazine (BA-a) and cyanate ester (BACY) were prepared via co-curing of benzoxazine with cyanate ester. DSC results manifested a multiple curing pattern with associated heat of reaction implying a co-reaction between oxazine moiety and cyanate group. The catalysis during the co-curing of blend was ascribed to the cycloaddition reaction between the two groups followed by the ring-opening of benzoxazine and cyclotrimerisation of cyanate ester. The spectral and analytical data supported the possibilities of further polymerization through the insertion of the phenolic OH of polybenzoxazine to cyanate group to form the intermediate iminocarbonate, which further induce curing of cyanate ester to form polycyanurate. A co-reacted network composed of triazine ring as a part of polybenzoxazine matrix is postulated. The co-reaction temperature diminished with increase in cyanate ester content in the blend. A single T_g was observed in DMTA of the cured matrix that implied a linked homogeneous matrix containing both triazine and polybenzoxazine. This was substantiated by the TGA, DTA and SEM behavior of the cured polymer. The modulus of the cured blend was higher than those of the component resins of the blend. The co-reaction with cyanate ester enhanced the high temperature stability of polybenzoxazine.     

Synthesis and amphiphilic properties of decanoyl esters of tri- and tetraethylene glycol

Well-defined decanoyl triethylene glycol ester and decanoyl tetraethylene glycol ester were synthesized and compared to their ether counterparts (C(10)E(4) and C(10)E(3)). Their physicochemical properties i.e. critical micelle concentrations (CMC), cloud points, and equilibrium surface tensions were determined. Binary water-surfactant phase behavior was also studied by polarized optical microscopy. The stability of the ester bond was determined by investigating alkaline hydrolysis of the compounds. It was found that CMC, cloud point and equilibrium surface tension are roughly the same for corresponding ethers and esters. In the binary diagram, the esters form only lamellar phases, the area of which is smaller than that of the ether counterparts. These different behaviors can be related to the modification of the molecular conformation induced by the replacement of the ether group by the ester group.     

Coloured complexes of all-trans-retinal with benzocaine and other local anaesthetics

Coloured Schiff base complexes with lambda max values of 500 nm or above were formed between the visual pigment all-trans-retinal and the local anesthetics procaine (lambda max = 533 nm), benzocaine (4-amino-benzoic acid ethyl ester, lambda max = 535 nm), 3-amino-benzoic acid ethyl ester (lambda max = 500 nm) and 2-amino-benzoic acid ethyl ester (lambda max = 509 nm) in methanol acidified with HCl. The anaesthetics lidocaine and urethane failed to form coloured compounds with lambda max values greater than 500 nm under the same conditions. The relevance of these observations to the effect of anaesthetics on the visual pigments is discussed.     

Substrate-assisted antibody catalysis

A new strategy in transition-state analog design is demonstrated to elicit catalytic antibodies. The strategy is based on substrate-assisted antibody catalysis and utilizes analogs designed to mimic the transition-state for intramolecular catalysis and thereby favor antibodies that can recruit catalytic groups from substrate. The hydrolysis of the benzoyl ester of cocaine provides an illustration. The benzoyl ester of cocaine is distant from the protonated nitrogen in the stable chair conformer but proximate in the strained boat form. An antibody stabilizing the boat form and approximating ester and amine could catalyze ester hydrolysis. To mimic the transition-state for the intramolecular catalysis, we synthesized a cocaine analog that replaces this ester with a methylenephenylphosphinate bridge to the tropane nitrogen. This bridged analog elicited 85 cocaine esterases out of 450 anti-analog antibodies-a performance markedly superior to that of a simple phosphonate ester-based analog with an identical tether. The correspondence of the analog to a "high energy" conformer eliminated product inhibition. For certain polyfunctional targets, substrate assistance can be an effective strategy for eliciting catalytic antibodies.     

Synthesis and properties of thiolactam analogs of pyrromethenones

Thiolactam analogs of kryptopyrromethenone and xanthobilirubic acid methyl ester were prepared from the parent pyrromethenone using Lawesson's reagent and are shown to form dimeric association complexes through intermolecular hydrogen bonding.     

Preparation of polysiloxanes from silicic acid. V. Condensation of silicic acid butyl esters and formation of silica fiber from the ester solutions

The condensation of silicic acid butyl esters was investigated by gel permeation chromatographic (GPC) analysis. The results revealed that the condensation was greatly dependent on a degree of esterification of the esters. The ester with the lowest degree of esterification underwent condensation to form a highly polymerized ester. It was found that fibers could be drawn from the ester solution before gelation.     

Thermoresponsive nanostructures by self-assembly of a poly(N-isopropylacrylamide)-lipid conjugate

The synthesis and purification of a poly(N-isopropylacrylamide)-lipid conjugate and its use in the preparation of a thermoresponsive lipid mesophase is described. Specifically, poly(N-isopropylacrylamide) with a single carboxyl group at one end was activated with dicyclohexylcarbodiimide/N-hydroxysuccinimide to form an active ester. This N-hydroxysuccinimide ester was then used to form a dimyristoyl-sn-glycero-3-phosphoethanolamine conjugate with poly(N-isopropylacrylamide) via an amide bond, rendering the conjugate amphiphilic. Quaternary phases comprising the conjugate, a phosopholipid, dimyristoylphosphatidylcholine, and a cosurfactant, N,N-dimethyldodecylamine-N-oxide, dispersed in water were found to self-assemble at room temperature to form liquid crystalline gels, adopting an expanded lamellar structure. A modest increase in temperature triggered the reversible conversion of the aggregate to a collapsed lamellar structure, while a modest reduction in temperature resulted in its conversion to a nonlamellar phase. The phases were characterized by polarized optical microscopy and small-angle X-ray scattering (SAXS).     

TiCl4-promoted direct N-acylation of sulfonamide with carboxylic ester

Several Lewis acids were investigated as promoters in the intermolecular or intramolecular direct N-acylation reaction of sulfonamides using carboxylic ester as an acylating agent. TiCl₄ was found to possess the highest activity and enhanced efficiently sulfonamide to form N-acylsulfonamides under optimized conditions. This method provides a novel approach to make N-acylsulfonamides from ester via an easy work-up procedure.     

Ester‐Mediated Amide Bond Formation Driven by Wet–Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth

Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α‐amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α‐hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α‐hydroxy acids and α‐amino acids form depsipeptides—oligomers with a combination of ester and amide linkages—in model prebiotic reactions that are driven by wet–cool/dry–hot cycles. Through a combination of ester–amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long‐standing hypothesis that peptides might have arisen from ester‐based precursors.