Methyl Ester Derivatives Research Articles

Robotized method for the quantification of fatty acids by gas–liquid chromatography

Analysis of fatty acid profile in fats and oils is conventionally performed by gas–liquid chromatography (GLC) as their fatty acid methyl ester (FAME) derivatives. Accurate quantification can be achieved by adding internal standard(s) prior to the derivatization step and calibration of the system using certified FAME mixture. GLC instruments equipped with online sample preparation units became recently commercially available and in theory can be used to improve laboratory productivity and safety. However, studies showing that this type of approach can be used to obtain reliable results are scarce. In the present study, we developed a method suitable for quantitative analysis of fatty acids in fats and oils by robotic preparation and online GLC analysis of FAME using methanolic potassium hydroxide as transmethylation reagent. The method has been validated on different fats and oils including milk fat, palm kernel, rapeseed and long‐chain polyunsaturated fatty acids containing oil samples. Method performance has been compared to the corresponding manual procedure and results show good repeatability [CV(r)<5%] and good intermediate reproducibility [CV(iR)<5%] in accordance with FDA guidelines. The results obtained show that transmethylation and GLC analysis of fats and oils can be robotized while remaining accurate and providing fatty acid data expressed as g of fatty acid per 100 g of sample. Compared to conventional methods, the volume of reagent and solvent is three times lower per sample analyzed with the robotized version which contributes to the reduction of waste and chemical risk exposure.

Characterization of esterified cassava starch with long alkyl side chains and different substitution degrees

The present work describes the characterization and thermal properties of hydrophobic starch obtained by the esterification of cassava starch with acyl imidazoles, acid chlorides and methyl ester derivatives of fatty acids with n-alkyl chains with 12–22 carbon atoms, in order to compare the dependence of their properties as a function of the length of the side chain and the methodology used for their synthesis. The n-acyl starches presented degrees of substitution (DS) between 0.06 and 1.2. Most of the derivatives obtained with acyl imidazoles were found to be stable at temperatures up to 300°C, whereas those synthesized with acid chlorides or methyl ester decomposed below. Finally, when the n-acyl starches were substituted with n-alkyl side chains of 16 or more carbon atoms, they were capable to crystallize in separate paraffinic phases independent of the starch backbone.

ENANTIOMER SEPARATION OF N-t-BOC AND N-CBZ α-AMINO ACIDS AND THEIR ESTERS ON POLYSACCHARIDE DERIVED CHIRAL STATIONARY PHASES

Liquid chromatographic enantiomer separation of N-t-BOC and N-CBZ α-amino acid, methyl ester, and ethyl ester derivatives was performed on chiral stationary phases (CSPs) based on polysaccharide derivatives. Good resolution of N-t-BOC and N-CBZ α-amino acid derivatives was achieved on Chiralcel OD, Chiralcel OF, and Chiralpak AD, respectively. Enantioselectivites of N-CBZ protected derivatives were found better than those of N-t-BOC protected derivatives. Moreover, the results of liquid chromatography and computational chemistry suggest that L-form is more retained in the case of carboxylic group of enantiomer locating toward to the inside of grooves, on the other hand, D-form is more retained in the case of alkyl group of α-position of N-protected α-amino acid derivatives locating toward to the inside of grooves.

Tuning Nanopore Formation of Oligocholate Macrocycles by Carboxylic Acid Dimerization in Lipid Membranes

Oligocholate macrocycles self-assemble into transmembrane nanopores by the associative interactions of water molecules inside the amphiphilic macrocycles. Macrocycles functionalized with a terephthalic acid "side chain" displayed significantly higher transport activity for glucose across lipid bilayers than the corresponding methyl ester derivative. Changing the 1,4-substitution of the dicarboxylic acid to 1,3-substitution lowered the activity. Combining the hydrophobic interactions and the hydrogen-bond-based carboxylic acid dimerization was an effective strategy to tune the structure and activity of self-assembled nanopores in lipid membranes.

Structure and Absolute Configuration of Methyl (3R)-Malonyl-(13S)-hydroxycheilanth-17-en-19-oate, a Sesterterpene Derivative from the Roots of Aletris farinosa

We report the isolation and structure elucidation of a new cheilanthane sesterterpene from the roots of Aletris farinosa that possesses an unusual malonate half-ester functional group. The structure of 1 was determined via mass spectrometry and 1D and 2D NMR spectroscopy, while its absolute configuration was determined via X-ray crystallographic analysis performed on its methyl ester derivative 2.

Synthesis and physiochemical property evaluation of carbamate derivatives of scutellarin methyl ester

A series of carbamate prodrugs of scutellarin methyl ester (4a–4e) were prepared in the presence of bis(trichloromethyl) carbonate (BTC) with scutellarin methyl esters and l-amino acid tert-butyl ester hydrochloride as starting materials. In vitro stability and aqueous solubility of target compounds were evaluated. The results indicated that compounds 4d and 4e have higher solubility and in vitro stability than scutellarin respectively.

AMR‐Me inhibits PI3K/Akt signaling in hormone‐dependent MCF‐7 breast cancer cells and inactivates NF‐κB in hormone‐independent MDA‐MB‐231 cells

AMR-Me, a C-28 methylester derivative of triterpenoid compound Amooranin isolated from Amoora rohituka stem bark and the plant has been reported to possess multitude of medicinal properties. Our previous studies have shown that AMR-Me can induce apoptosis through mitochondrial apoptotic and MAPK signaling pathways by regulating the expression of apoptosis related genes in human breast cancer MCF-7 cells. However, the molecular mechanism of AMR-Me induced apoptotic cell death remains unclear. Our results showed that AMR-Me dose-dependently inhibited the proliferation of MCF-7 and MDA-MB-231 cells under serum-free conditions supplemented with 1 nM estrogen (E2) with an IC50 value of 0.15 µM, 0.45 µM, respectively. AMR-Me had minimal effects on human normal breast epithelial MCF-10A + ras and MCF-10A cells with IC50 value of 6 and 6.5 µM, respectively. AMR-Me downregulated PI3K p85, Akt1, and p-Akt in an ERα-independent manner in MCF-7 cells and no change in expression levels of PI3K p85 and Akt were observed in MDA-MB-231 cells treated under similar conditions. The PI3K inhibitor LY294002 suppressed Akt activation similar to AMR-Me and potentiated AMR-Me induced apoptosis in MCF-7 cells. EMSA revealed that AMR-Me inhibited nuclear factor-kappaB (NF-κB) DNA binding activity in MDA-MB-231 cells in a time-dependent manner and abrogated EGF induced NF-κB activation. From these studies we conclude that AMR-Me decreased ERα expression and effectively inhibited Akt phosphorylation in MCF-7 cells and inactivate constitutive nuclear NF-κB and its regulated proteins in MDA-MB-231 cells. Due to this multifactorial effect in hormone-dependent and independent breast cancer cells AMR-Me deserves attention for use in breast cancer prevention and therapy.

Effects of Synthetic Peptides on the Inflammatory Response and their Therapeutic Potential

Recently, interest in small peptide molecules as potential drug candidates has revived. In this review, two series of synthetic peptides and their selective effects on the inflammatory response have been described, focusing on the intracellular pathways involved and on their therapeutic potential. A series of F(D)LF(D)LF analogs has been synthesized, including either N- t-Boc or different N-ureido substituents. The free acid derivatives as they are good candidates as antiinflammatory drugs are able to antagonize the multiple neutrophil functions evoked by N-formyl-L-methionyl-L-leucyl-Lphenylalanine (fMLF), i.e. chemotaxis, superoxide anion production and lysozyme release. Their methyl-ester derivatives are ineffective. The second series of peptides derives from the endogenous protein kinase C (PKC) inhibitor PKI55, a 55-amino acid protein, whose synthesis is induced by PKC activation, so that a feedback loop of inhibition is established. In vitro experiments showed that PKI55 inhibits recombinant PKC isoforms α, β1, β2, γ, δ, ζ, ; to identify the minimal amino acid sequence of PKI55 protein maintaining the inhibitory effects on PKC, peptides derived from both C- and N-terminal sequences have been synthesized. The N-terminal peptides 5 (MLYKLHDVCRQLWFSC), 8 (CRQLWFSC) and 9 (CRQLW), that in human neutrophils retain the inhibitory activity on PKC, decrease the chemotaxis, and, in mice, display anti-inflammatory and analgesic action, after both central and peripheral administration of very low doses. Furthermore, the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro, favouring the recovery of synaptic function. These findings suggest interesting possible therapeutic applications for these peptides.

Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation

In this study, target compounds 5–12 were synthesized via acid amine coupling of ibuprofen and naproxen with methyl ester derivatives of amino acids, namely, l-proline, sarcosine, l-tyrosine, and l-glutamic acid. When tested for anti-inflammatory activity using the acute carrageenan-induced hind paw method in rats, compounds 5–12 showed significantly greater anti-inflammatory activity, in the range of 40.64%–87.82%, compared with a placebo control group (P < 0.001). Among the newly synthesized compounds 5–12, naproxen derivatives 9–12 with anti-inflammatory activity ranging between 66.99% and 87.82% showed significantly higher (P < 0.05) potency than ibuprofen derivatives 5–8 with inhibition in the range of 22.03%–52.91% and control groups of ibuprofen (76.34%) or naproxen (75.59%, P < 0.05). Moreover, derivatives 9–12 derived from naproxen, in particular compounds 9 and 10 which achieved 83.91% and 87.82% inhibition of inflammation, respectively, showed significantly (P < 0.05) higher potency than naproxen derivatives 11 and 12. Notably, among naproxen derivatives 9–12, the gastric ulcerogenicity for 9 (ulcer index 11.73) and 10 (ulcer index 12.30) was found to be significantly lower (P < 0.05) than that of the active ibuprofen and naproxen control groups with ulcer indices of 22.87 and 24.13, respectively. On the other hand, naproxen derivatives 9–11 showed significant inhibition (P < 0.05) of prostaglandin E2 synthesis when compared with the active control group receiving indomethacin, suggesting a correlation between the observed low ulcerogenicity and effect on prostaglandin E2 synthesis for compounds 9 and 10. However, significant inhibition of prostaglandin E2 observed for naproxen derivative 11 (107.51) did not correlate with its observed ulcer index (16.84). Our overall findings for carbamoylmethyl ester derivatives named 5–12 clearly suggest that the compounds showing potent antiinflammatory effect.

Photochemical electrocyclic ring closure and leaving group expulsion from N-(9-oxothioxanthenyl)benzothiophene carboxamides

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG(-) = Cl(-), PhS(-), HS(-), PhCH(2)S(-)) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG(-). The LG(-) photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH(3)CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01-0.04, depending on LG(-) basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG(-) is thought to occur once this species converts to the closed shell ground state.

Application of supercritical carbon dioxide–co-solvent mixtures for removal of organic material from archeological artifacts for radiocarbon dating

Archeological artifacts such as burial and embalmment materials are commonly dated by 14C labeling using accelerator mass spectrometry (AMS). The presence of contaminant organic matter can interfere with the accurate determination of an object's age, hence sample preparation is a critical step before radiocarbon-based dating. Both harsh acid and base treatments have been applied to remove contamination, such as humic acids, resin-based adhesives, and plant oils. Additional removal of carbon-laden material can also be affected by applying such methods as plasma oxidation. In this study, SC-CO2 with addition of a cosolvent has been applied to remove the above materials prior to plasma oxidation and subsequent dating via AMS. Initially, wood/charcoal samples were extracted using a modified-Isco SFX-2-10 extraction unit (Isco Inc., Lincoln, NE). Experiments were conducted using supercritical carbon dioxide/10% methanol at a pressure of 20.4MPa (3000psig) (pr=2.80) and 40°C (Tr=1.36), and carbon dioxide flow rates of ∼1.4±0.1ml/min. Comparison of the SC-CO2–methanol cosolvent treatment with traditional acid–base–acid sample pretreatment on identical wood-charcoal samples showed comparable radiocarbon dating results encompassing a period of 10,000 years. In addition, both Russian and Egyptian mummy gauzes and Russian textiles were similarly treated and the extracts analyzed by MALDI-TOF-MS and GC/MS to determine the chemical identity of the extracted material. A polyglycerol-based polymer was positively identified in addition to fatty acid moieties as their fatty acid methyl ester derivatives (FAMES), which potentially formed from the in situ reaction of the triglycerides present in the embalment materials with the SC-fluid mixture. Model extractions from spiked-linen gauze samples have verified removal of such materials as beeswax, coconut oil, frankincense, glycerol, and humic acids in varying amounts. Application of supercritical fluid extraction (SFE) appears to be a promising method to pretreat small samples for 14C radiocarbon dating where conservation of the archeological artifact is of importance. The SFE pretreatment has the potential to replace harsh acid–base pretreatment methods, and can be coupled with a non-destructive argon or oxygen plasma treatment for microgram carbon removal prior to accelerator MS isotope ratio age determination of the archeological artifact. This combination of techniques requires as little as 0.05mg of carbon-equivalent weight for the age determination of the artifact while minimizing sample degradation.

English

The Ammi visnaga seeds oil constituents of methyl ester derivatives of fatty acids were analyzed using gas chromatography coupled with mass spectrometer. The results obtained contain saturated as well as unsaturated fatty acids of A. visnaga seeds oils. A total of 15 different components were identified and quantified. Methyl ester of oleic acid was found in high concentration (13.30%) among the identified analytes of interest. In addition, methyl ester of linoleic acid (11.39%), palmitic acid (7.88%) and stearic acid (1.88%) were found. Concentration of the rest of identified fatty acids analytes were less than 1%. Thus, from the results it is apparent that the therapeutic efficacy of the plant may be due to the presence of high percentage of valuable analytes concentrations detected in the fatty acid of A. visnaga. The reason for the consumption in the pharmaceuticals as well as its wide applications in the prevention of dental carries, for various skin diseases and different infections. Key words: Ammi visnaga, methyl ester, fatty acid, gas chromatography (GC), analyte.

Biosynthesis, isolation, and NMR analysis of leukotriene A epoxides: substrate chirality as a determinant of the cis or trans epoxide configuration

Leukotriene (LT)A₄ and closely related allylic epoxides are pivotal intermediates in lipoxygenase (LOX) pathways to bioactive lipid mediators that include the leukotrienes, lipoxins, eoxins, resolvins, and protectins. Although the structure and stereochemistry of the 5-LOX product LTA₄ is established through comparison to synthetic standards, this is the exception, and none of these highly unstable epoxides has been analyzed in detail from enzymatic synthesis. Understanding of the mechanistic basis of the cis or trans epoxide configuration is also limited. To address these issues, we developed methods involving biphasic reaction conditions for the LOX-catalyzed synthesis of LTA epoxides in quantities sufficient for NMR analysis. As proof of concept, human 15-LOX-1 was shown to convert 15S-hydroperoxy-eicosatetraenoic acid (15S-HPETE) to the LTA analog 14S,15S-trans-epoxy-eicosa-5Z,8Z,10E,12E-tetraenoate, confirming the proposed structure of eoxin A₄. Using this methodology we then showed that recombinant Arabidopsis AtLOX1, an arachidonate 5-LOX, converts 5S-HPETE to the trans epoxide LTA₄ and converts 5R-HPETE to the cis epoxide 5-epi-LTA₄, establishing substrate chirality as a determinant of the cis or trans epoxide configuration. The results are reconciled with a mechanism based on a dual role of the LOX nonheme iron in LTA epoxide biosynthesis, providing a rational basis for understanding the stereochemistry of LTA epoxide intermediates in LOX-catalyzed transformations.

β-Cyclodextrin derivative as chiral carrier in membrane transport of some aromatic amino acids

The chiral functionalized β-cyclodextrin (heptakis (2,3,6-tri-o-acetyl)-β-cyclodextrin) was studied as an extraction receptor in liquid–liquid extraction and carrier through bulk liquid membrane for highlighting its ability to enantiomeric discrimination of some native aromatic amino acids (tryptophane, phenylalanine, and tyrosine) and methylester derivatives (tryptophane methylester hydrochloride, phenylalanine methylester hydrochloride, and tyrosine methylester hydrochloride). The receptor exhibited carrier ability for aromatic amino acids transport through chloroform liquid membrane, especially for l-amino acids form aiming at their separation. Active transport of amino acids assisted by the pH gradient was carried out. Additional, the circular dichroism measurements were performed to point out the enantiomeric discrimination of aromatic amino acids by functionalized β-cyclodextrin. The results showed that the structural properties of amino acids are an important parameter in extraction and transport experiments.

The mystery of the ‘resin-of-canuaru’: A medicine used by caboclos river-dwellers of the Amazon, Amazonas, Brazil

Ethnopharmacological relevance‘Resin-of-canuaru’ is a medicine utilized by caboclos living in the Amazon Region, Brazil. There is a mystery regarding its origin because the caboclos maintain that this substance is derived only from animal secretions (from a frog called canuaru), whereas the historic literature claims that ‘resin-of-canuaru’ is derived solely from a plant exudate (resin). Based on our ethnographic studies, we hypothesized that this substance is a combination of both. Because the past reports on this resiniferous material in the literature are based solely on observations, we aimed to present ethnographic, zoological and chemical data to try to elucidate the origin of the ‘resin-of-canuaru’. Materials and methodsEthnographic techniques and methods were applied, including participant observation, the use of field diaries and informal and unstructured interviews. The canuaru frog (Trachycephalus resinifictrix Goeldi, 1907) and ‘resin-of-canuaru’ were collected for taxonomic identification and chemical analysis, respectively. The resiniferous ‘resin-of-canuaru’ was extracted using MeOH and then analyzed by silica gel TLC and NMR. ResultsCanuaru frogs live in tree cavities and secrete a large amount of substances during spawning, resulting in a resiniferous material. NMR analysis of the MeOH extract of this crude material showed peaks assigned to 3,4-secofriedel-4(23)-en-3-oic acid (putranjuvic acid) and its methyl ester derivative (methyl putranjivate) and to biogenetic precursor of these two compounds (a lactone derivative), which is formed by the oxidation of friedelin. Based on evidence that Protium species accumulate primarily tetracyclic/pentacyclic triterpenoids and that the co-occurrence of the compounds listed above is rarely described in plant species, we suggest that these compounds could be products of the biotransformation of friedelin by the frog. ConclusionsAccording to our data, the ‘resin-of-canuaru’ seems to have both animal and vegetal origins.

The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer

Novel drugs and drug combinations are needed for the chemoprevention and treatment of cancer. We show that the histone deacetylase inhibitor vorinostat [suberoylanilide hydroxamic acid (SAHA)] and the methyl ester or ethyl amide derivatives of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me and CDDO-Ea, respectively) cooperated to inhibit the de novo synthesis of nitric oxide in RAW 264.7 macrophage-like cells and in primary mouse peritoneal macrophages. Additionally, SAHA enhanced the ability of synthetic triterpenoids to delay formation of estrogen receptor-negative mammary tumors in MMTV-polyoma middle T (PyMT) mice. CDDO-Me (50 mg/kg diet) and SAHA (250 mg/kg diet) each significantly delayed the initial development of tumors by 4 (P < 0.001) and 2 (P < 0.05) weeks, respectively, compared with the control group in the time required to reach 50% tumor incidence. CDDO-Ea (400 mg/kg diet), as a single agent, did not delay tumor development. The combination of either triterpenoid with SAHA was significantly more potent than the individual drugs for delaying tumor development, with a 7 week (P < 0.001) delay before 50% tumor incidence was reached. SAHA, alone and in combination with CDDO-Me, also significantly (P < 0.05) inhibited the infiltration of tumor-associated macrophages into the mammary glands of PyMT mice and levels of the chemokine macrophage colony-stimulating factor in primary PyMT tumor cells. In addition, SAHA and the synthetic triterpenoids cooperated to suppress secreted levels of the pro-angiogenic factor matrix metalloproteinase-9. Similar results were observed in mouse models of pancreatic and lung cancer. At concentrations that were anti-inflammatory, SAHA had no effect on histone acetylation. These studies suggest that both SAHA and triterpenoids effectively delay tumorigenesis, thereby demonstrating a promising, novel drug combination for chemoprevention.

Exploitation of a Laccase/Meldola’s Blue System for NAD+ Regeneration in Preparative Scale Hydroxysteroid Dehydrogenase‐Catalyzed Oxidations

AbstractAn enzymatic regeneration system consisting of laccase and the 2H+/2e− redox mediator Meldola’s blue (MB) was developed for the efficient oxidation of reduced nicotinamide adenine dinucleotide (NADH) cofactor and employed in the gram‐scale oxidation of cholic acid (1) to its 7‐keto derivative (1a) by 7α‐hydroxysteroid dehydrogenase (7α‐HSDH) in an aqueous, buffered reaction system. The regenerating enzyme, laccase, reduces molecular oxygen as terminal 4H+/4e− acceptor to water and concomitantly reoxidizes NADH via MB at high turnover rates. The regeneration system was successfully applied to quantitatively convert 1 (50 mM, 20.4 g) into 1a with a space‐time yield of 5.8 mmol L−1 h−1. High total turnover numbers were achieved for 7α‐HSDH (4.2×105) and laccase (1.1×106). Alternatively, the regeneration system was employed on the conversion of the methyl ester derivative of cholic acid (2, 200 mM, 5.9 g) dissolved in isopropyl acetate as organic solvent in a biphasic system. Due to the high concentration of 2 and the excellent performance of the enzymatic cascade reaction even under the harsh process conditions, space‐time yields of up to 20 mmol L−1 h−1 (8.5 g L−1 h−1) of the produced 7‐keto derivative 2a were obtained. The irreversibility and high driving force of the regenerating reaction allowed quantitative conversions and easy product recovery.

Analytical Characterization of Fatty Acids Composition of Bioactive Stem Oil of Maytenus royleanus by Gas Chromatography Mass Spectrometry

AbstractThe significant inhibition and selectivity for human solid tumor cell by oily fraction of Maytenus royleanus, was subjected to GC‐MS analysis for determination of its chemical constituents. GC‐MS profile of methyl ester derivatives of fatty acids, showed that Palmitic acid (35.41%), Oleic acid (10.91%), Stearic acid (5.31%), Margaric acid (5.13%), Behenic acid (5.18%) and Hexanoic acid (4.97%) were the major components in the isolated oily fraction, while rest of the other fatty acids were present in minor concentration. The literature revealed that no such work has been done for the determination of fatty acids in M. royleanus stem oil.

A statistical investigation of biodiesel physical and chemical properties, and their correlation with the degree of unsaturation

Abstract In the present work, a detailed statistical investigation is conducted in order to a) assess the average values of all properties (incl. fatty acid composition) of the most investigated biodiesels and b) quantify the effects of feedstock unsaturation on the physical and chemical properties of the derived methyl ester. To this aim, the available literature on biodiesel properties and fatty acid composition was gathered (more than 750 papers published in International Journals and Conferences), and the reported measurements are statistically analyzed with respect to the feedstock and its chemical composition and structure; in total, 26 different biodiesel feedstocks are studied, comprising of twenty-two edible and non-edible vegetable oils and four animal fats. From the analysis, collective results and statistical data are derived for each property that are then compared with the European and American specifications. The effects of unsaturation are investigated with separate best-fit linear curves provided for each interesting property with respect to the average number of double bonds. The various trends observed are discussed and explained based on fundamental aspects of fuel chemistry and on the consequences they have on real engine operation.

Synthesis and Reactions of New Chiral Linear and Macrocyclic Tetraand Penta-peptide Candidates

9a A series of linear and macrocyclic pentapeptide derivatives have been prepared via the coupling of pyridine-2,6-dicarboxylic acid (1) or pyridine-2,6-dicarbonyl dichloride (2) with appropriate amino acid methyl esters. The coupling of 1or 2with aminoacid methyl esters gave the corresponding pyridine dipeptide methyl esters 3, which were hydrolyzed with sodium hydroxide to the corresponding acids 4. The latter compounds 4were coupled with other amino acid methyl esters to afford the corresponding tetrapeptide esters 5, which were hydrolyzed with sodium hydroxide to the corresponding acids 6. Cyclization of tetrapeptide acids with L-lysine methyl ester or with aliphatic diamide derivatives afforded the corresponding cyclic pentapeptide methyl ester derivatives 7and cyclic tetrapeptide diamines 8, respectively. Finally, hydrolysis with 1 N sodium hydroxide or hydrazinolysis with hydrazine hydrate of methyl esters 7afforded the corresponding acids - e and hydrazides 10a - e, respectively