Amino acids: Building blocks for the synthesis of greener amphiphiles

Amino acid-based amphiphiles have attracted much attention as environmentally friendly surfactants because of their biodegradability, low toxicity and the use of renewable sources of raw materials for their syntheses. With respect to molecular design, the amino acid-based architecture allows the possibilities of multiple structures of amphiphiles with varying head groups and chain lengths. This review focuses on the synthetic strategies for the development of various types of surfactants derived from amino acids. Their properties in terms of surface, biological and catalytic activities are illustrated.     

Towards practical biocatalytic Baeyer-Villiger reactions: applying a thermostable enzyme in the gram-scale synthesis of optically-active lactones in a two-liquid-phase system

Baeyer-Villiger monooxygenases (BVMOs) are extremely promising catalysts useful for enantioselective oxidation reactions of ketones, but organic chemists have not used them widely due to several reasons. These include instability of the enzymes in the case of in vitro and even in vivo systems, reactant/product inhibition, problems with upscaling and the necessity of using specialized equipment. The present study shows that the thermally stable phenylacetone monooxygenase (PAMO) and recently engineered mutants can be used as a practical catalysts for enantioselective Baeyer-Villiger oxidations of several ketones on a preparative scale under in vitro conditions. For this purpose several parameters such as buffer composition, the nature of the solvent system and the co-factor regeneration system were optimized. Overall a fairly versatile and efficient catalytic system for enantioselective laboratory scale BV-oxidations of ketones was developed, which can easily be applied even by those organic chemists who are not well versed in the use of enzymes.     

Enzyme-catalyzed synthesis of aliphatic polyesters in organic media: Study of transesterification equilibrium shift and characterization of cyclic compounds

Enzyme-catalyzed synthesis of aliphatic polyesters in organic media from methyl diesters and diols was carried out at stoechiometric ratio in the presence of supported lipases (li-pozyme^® and novozyme^®). Two systems were studied to shift the thermodynamic equilibrium which limits the conversion. In the first one, the solution flows through a molecular sieve in which methanol is adsorbed. In the second one, methanol is eliminated by nitrogen bubbling. The system with nitrogen bubbling in hydrophobic solvents at 60°C works best when novozyme^® is used as catalyst. Despite a high fractional conversion (p> 0.99), the number-average molar mass is not very high (M?;_n = 3050 eq. PS). In relation to the nature of monomers, cycles with DP = 2–20 were characterized by chromatographic analyses and mass spectrometry. Their formation explains why high polycondensates cannot be obtained. © 1995 John Wiley & Sons, Inc.     

聚乳酸与聚乳酸-羟基乙酸多孔细胞支架的制备及孔隙的表征

应用溶液烧铸致孔剂浸出技术制备了不同致孔剂用量与不同致孔剂颗粒尺寸条件下的一系列聚乳酸及不同组成的聚乳酸－羟基乙酸多孔细胞支架;用一种改进的方法－重量法测定其孔隙率;在聚乳酸－羟基乙酸多孔支架上进行了软骨细胞培养。研究结果表明,随着制备过程中致孔剂用量的增加,多孔支架的孔隙逐渐增加,而与致孔剂的颗粒大小基本无关;致孔剂的颗粒大小只影响多孔支架的孔径;在致孔剂用量及致孔剂颗粒尺寸都相同的情况下,随着共聚物中乙交酯含量的增加,孔隙率逐渐下降;软骨细胞在支架上繁殖情况良好,三周后已开始分泌细胞外基质。     

Continuous production of lactic acid in a cell recycle reactor

The production of lactic acid from glucose has been demonstrated using a CSTR (continuous stirred-tank reactor) with cell recycle. Studies were conducted withLactobacillus delbrueckii at a fermentation temperature of 42°C and a pH of 6.25. A cell density of 140 g dry weight/L and a volumetric productivity of 150 g/L.h, with complete glucose consumption, were obtained. It was not possible to obtain a lactic acid concentration above 60 g/L because of product inhibition. A cell purge was not necessary to maintain high viability bacteria culture or to obtain a steady state. At steady state the net cell growth appeared to be negligible. The specific glucose consumption for cell maintenance was 0.33 g glucose/g cells-h.     

Current advances in microbial cell factories for lactate-based polyesters driven by lactate-polymerizing enzymes: Towards the further creation of new LA-based polyesters

Polylactic acid (PLA), a representative bio-based polyester, has been commonly synthesized via a multi-step by chemical process. The current modes of generating PLA involve microbial fermentation of starting material, lactic acid (LA), followed by chemical ring-opening polymerization. Recently, one-pot complete bioprocess for LA-based polyesters has been established as a microbial cell factory (MCF). The concept is a process conversion from the usual chemical factory to the MCF. This new challenge was triggered by discovery of an engineered LA-polymerizing enzyme (LPE). The LPE was found as one of the members of an extensive mutant library that has been created through the long-term evolutionary engineering study of natural biopolyester-synthesizing enzymes. Needless to say, a strategic method of getting the beneficial mutation in the enzyme is of the utmost importance and an essential step towards accomplishing the desired purpose, the acquisition of the LA-polymerizing activity in this case. In this review, the structures and properties of LPE-catalyzed polymerization products will be discussed as well as backgrounds on establishment of the MCFs for synthesis of LA-based polyesters. Also, experimental strategies for enrichment of the LA fraction will be proposed to further advance the prototype of MCF based on the related metabolic pathways.     

Towards a biomimetic synthesis of barrenazine A

We report herein a concise and biomimetic synthesis of a precursor of barrenazine A, a cytotoxic alkaloid. The C₂-symmetry of this molecule suggested the dimerization of an aminoketone, as the precursor of the central core pyrazine. This compound was prepared by assembly of aspartic acid and glycine.     

One‐step synthesis of poly(lactic‐co‐glycolic acid)‐g‐poly‐1‐vinylpyrrolidin‐2‐one copolymers

The radical polymerization of 1‐vinylpyrrolidin‐2‐one (NVP) in poly(lactic‐co‐glycolic acid) (PLGA) 50:50 at 100 °C leads to amphiphilic PLGA‐g‐PVP copolymers. Their composition is determined by FT‐IR spectroscopy. Thermogravimetric analyses agree with FT‐IR determinations. Saponification of the PLGA‐g‐PVP polyester portion allows isolating the PVP side chains and measuring their molecular weight, from which the average chain transfer constant (C_T) of the PLGA units is estimated. The MALDI‐TOF spectra of PVP reveal the presence at one chain end of residues of either glycolic acid‐ or lactic acid‐ or lactic/glycolic acid dimers, trimers and one tetramer, the other terminal being hydrogen. This unequivocally demonstrates that grafting occurred. Accordingly, the orthogonal solvent pair ethyl acetate—methanol, while separating the components of PLGA/PVP intimate mixtures, fails to separate pure PVP or PLGA from the reaction products. All PLGA‐g‐PVP and PLGA/PLGA‐g‐PVP blends, but not PLGA/PVP blends, give long‐time stable dispersions in water. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1919–1928     

The study of biocatalyzed thio-Michael reaction: a greener and multi-gram protocol

This Letter introduces a new, cheap and green protocol for the thio-Michael reaction. Here we applied three free enzymes such as lipase from pancreas porcine, chymosin and papain and an immobilized one: the Liposyme®. The reactions were executed at room temperature and resulted in the thio-Michael adduct in good or excellent yields. The protocol describes the use of EtOH as solvent and a less percentage of enzymes, which is in concordance with the green chemistry topics, so we can mention that chymosin and papain were used as biocatalyst in an organic reaction for the first time in this Letter.     

Polystyrene sulfonic acid catalyzed greener synthesis of hydrazones in aqueous medium using microwaves

An environmentally benign aqueous protocol for the synthesis of cyclic, bi-cyclic, and heterocyclic hydrazones using polystyrene sulfonic acid (PSSA) as a catalyst has been developed; the simple reaction proceeds efficiently in water in the absence of any organic solvent under microwave irradiation and involves basic filtration as the product isolation step.     

Effect of gamma‐irradiation sterilization on the physical and mechanical properties of a hybrid wound dressing

A wound dressing should ideally provide an optimal healing environment which enables rapid healing. It should maintain a moist environment at the wound surface, allow gas exchange, act as a barrier to microorganisms, remove excess exudates and afford mechanical protection to the wound. A new bioresorbable hybrid wound dressing which combines a poly(DL‐lactic‐co‐glycolic acid) porous top layer with a spongy collagen sublayer was developed and studied. The top layer contained the antibiotic drug gentamicin for controlled release to the wound site. It is of very high importance to use an appropriate sterilization process for this special new wound dressing, which will not have a deleterious effect on its function. Our investigation therefore focused on the effects of gamma‐irradiation sterilization (10, 25, 35 and 50 kGy) on the structure properties of this wound dressing. The physical and mechanical properties were of the wound dressings were affected by the gamma irradiation because of a combination of chain scission and crosslinking of the collagen layer mainly. The weight loss and water vapor transmission rate were increased, while the water uptake was decreased with the increase in the irradiation dose. The changes were small when doses of 10 or 25 kGy were applied at room temperature. The gamma‐irradiation resulted in stronger but more brittle wound dressings. These trends were smaller when the sterilization process was carried out in liquid nitrogen. Our research shows that gamma‐sterilization process is feasible for our new concept of hybrid wound dressings and optimal conditions can be chosen. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

脂肪酶催化乳酸与乙醇合成乳酸乙酯的反应动力学

对脂肪酶催化乳酸与乙醇合成乳酸乙酯反应的动力学进行了研究,根据乒乓机制和双底物抑制的特性建立了反应速率方程.反应时间常数(tR)和扩散时间常数(tD)的计算结果表明,酯化反应速率未受到明显的限制.反应速率方程可以很好地预测实验结果,由非线性拟合得到的动力学参数中,乳酸(A)和乙醇(B)的抑制常数分别为KiA=10.7mmol/L和KiB=275.0mmol/L.这说明乳酸作为短链极性脂肪酸,对酶的失活作用远大于乙醇.乳酸在微液层中聚集并产生了使酶失活的低pH值环境,同时在酯化反应中存在竞争性抑制作用.     

Enzymatic polymerization: A new method of polymer synthesis

Enzymatic polymerization denotes an in vitro polymerization via nonbiosynthetic pathways catalyzed by an isolated enzyme. This article describes the recent progress of this polymerization technique, developed mainly during this decade. The polymerization utilizes enzymes of hydrolases and oxidoreductases as catalysts. This new method of polymer synthesis provided natural polysaccharides like cellulose, amylose, xylan, and chitin, and unnatural polysaccharides catalyzed by a glycosidase from well-designed monomers, various functionalized polyesters catalyzed by lipase from a variety of monomers, and polyaromatics materials catalyzed by an oxidoreductase and an enzyme model complex from phenols and anilines. An oxidoreductase also initiated vinyl polymerizations. Characteristic features of enzymatic polymerizations are discussed, including the importance of the combination of substrate monomer and enzyme. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3041–3056, 1999     

Sodium dodecyl sulfate in water: greener approach for the synthesis of quinoxaline derivatives

Abstract

A mild and efficient synthetic method has been developed for the preparation of biologically important quinoxalines in excellent yield from relatively safe precursor α-bromoketones and 1,2-diamines using catalytic amount of micellar sodium dodecyl sulfate in water at ambient temperature. The method is also found effective for the introduction of quinoxaline moiety into the ring A of pentacyclic triterpenoid, friedelin. Ambient reaction conditions, renewable catalytic condition, inherently safer chemistry, excellent product yields, and water as a reaction medium display both economic and environmental advantages.     

Fullerene C60 as a stabilizer in the synthesis of liquid-crystalline polyesters

It has been shown that owing to the use of fullerene C₆₀ (～0.01 wt % based on the monomer weight) as a stabilizer in the synthesis of a liquid-crystalline (LC) polyesters via high-temperature acceptorless poly-condensation, the temperature interval of reaction may be widened to 220°C and the crosslinking side reactions may be eliminated.     

Towards the optimal screening collection: a synthesis strategy

The development of effective small-molecule probes and drugs entails at least three stages: 1) a discovery phase, often requiring the synthesis and screening of candidate compounds, 2) an optimization phase, requiring the synthesis and analysis of structural variants, 3) and a manufacturing phase, requiring the efficient, large-scale synthesis of the optimized probe or drug. Specialized project groups tend to undertake the individual activities without prior coordination; for example, contracted (outsourced) chemists may perform the first activity while in-house medicinal and process chemists perform the second and third development stages, respectively. The coordinated planning of these activities in advance of the first small-molecule screen tends not to be undertaken, and each project group can encounter a bottleneck that could, in principle, have been avoided with advance planning. Therefore, a challenge for synthetic chemistry is to develop a new kind of chemistry that yields a screening collection comprising small molecules that increase the probability of success in all three phases. Although this transformative chemistry remains elusive, progress is being made. Herein, we review a newly emerging strategy in diversity-oriented small-molecule synthesis that may have the potential to achieve these challenging goals.     

Towards understanding the increase in strength of thermotropic polyesters with heat treatment

Thermotropic copolyester fibers of oxynaphthoate and oxybenzoate have been subjected to conditions that promote solid-state polymerization as well as annealing. The annealing process causes the crystals to perfect with a simultaneous increase in heat of fusion and melting temperature. Solid-state polymerization, a reaction rate-controlled process, causes the polymer viscosity average molecular weight to increase by chain extension from about 14,000 g/mole to more than 87,000 g/mole with a simultaneous impressive increase in tenacity from about 10 g/d (1.2 GPa) to almost 30 g/d (3.7 GPa). To understand the changes in mechanical properties, we have modeled the fiber structure as short rod-like molecules poorly bonded to a continuous matrix of parallel molecules. Lengthening of the reinforcing molecules facilitates better transfer of load from matrix to molecules, resulting in higher tenacity fibers. © 1994 John Wiley & Sons, Inc.     

Immobilization ofLactobacillus bulgaricus in a hollowfiber bioreactor for production of lactic acid from acid whey permeate

Lactobacillus bulgaricus was immobilized in the shell side of an industrial hollow-fiber ultrafiltration module. Acid whey permeate, containing 46 g/L lactose supplemented with 10 g/L yeast extract, was pumped through the tube side at dilution rates of 0.2–2.5/h. At a cell concentration of 100 g/L, productivity was 1.5–5 g lactic acid/L/h.