N,N-Diprotected dehydroamino acid derivatives: versatile substrates for the synthesis of novel amino acids

Non-proteinogenic amino acids are an important class of organic compounds that can have intrinsic biological activity or can be found in peptides with antiviral, antitumor, anti-inflammatory or immunosuppressive activities. This type of compounds is also important in drug development, in the elucidation of biochemical pathways and in conformational studies. Therefore, research towards efficient methods that allow the synthesis of these compounds constitutes an important area of peptide chemistry. In our laboratories we have developed a new and high yielding method for the synthesis of N,N-diprotected dehydroamino acid derivatives using tert-butyl pyrocarbonate and 4-dimethylaminopyridine. These compounds were used as substrates in several types of reactions, allowing the synthesis of a variety of new amino acid derivatives. Some of these new compounds are heterocyclic systems or contain heterocyclic moieties such as pyrazole, indole, or imidazole. Thus, several nitrogen heterocycles were reacted with N,N-diprotected dehydroalanine to give new beta-substituted alanines and dehydroalanines. Furanic amino acids were obtained treating the methyl ester of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl) dehydroalanine with carbon nucleophiles of the beta-dicarbonyl type having at least one methyl group attached to one of the carbonyl groups. Treatment of these furanic amino acids with trifluoracetic acid afforded pyrrole derivatives in good to high yields. A N,N-diprotected 1,4-dihydropyrazine was obtained reacting the methyl ester of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl)dehydroalanine with 4-dimethylaminopyridine and an excess of potassium carbonate. Tetrahydropyrazines were synthesized by reaction of this 1,4-dihydropyrazine derivative with nucleophiles or by electrochemical reduction. Cleavage of the N-protecting groups from the 1,4-dihydropyrazine gave a disubstituted pyrazine. This review covers the synthesis of N,N-diprotected dehydroamino acids and their application as precursors for the synthesis of newFEDER - Federación Española de Enfermedades Raras (POCI/QUI/59407/2004

A robust feature extraction for automatic speech recognition in noisy environments

This paper presents a method for extraction of speech robust features when the external noise is additive and has white noise characteristics. The process consists of a short time power normalisation which goal is to preserve as much as possible, the speech features against noise. The proposed normalisation will be optimal if the corrupted process has, as the noise process white noise characteristics. With optimal normalisation we can mean that the corrupting noise does not change at all the means of the observed vectors of the corrupted process. As most of the speech energy is contained in a relatively small frequency band being most of the band composed by noise or noise-like power, this normalisation process can still capture most of the noise distortions. For Signal to Noise Ratio greater than 5 dB the results show that for stationary white noise, the normalisation process where the noise characteristics are ignored at the test phase, outperforms the conventional Markov models composition where the noise is known. If the noise is known, a reasonable approximation of the inverted system can be easily obtained performing noise compensation still increasing the recogniser performance

Catches in ghost-fishing octopus and fish traps in the northeastern Atlantic Ocean (Algarve, Portugal)

Ghost fishing is the term used to describe the continued capture of fish and other living organisms after a fisherman has lost all control over the gear. Traps may be lost for a variety of reasons including theft, vandalism, abandonment, interactions with other gear, fouling on the bottom (i.e., traps and ropes are caught on rocky substrate), bad weather, and human error (Laist, 1995). Annual trap loss can be as high as 20% to 50% of fished traps in some fisheries (Al-Masroori et al., 2004). Because lost traps can continue to fish for long periods, albeit with decreasing efficiency over time (e.g., Smolowitz, 1978; Breen, 1987, 1990; Guillory, 1993), ghost fishing is a concern in fisheries worldwide

Synthesis and reactivity of a 1,4-dihydropyrazine derivative

N,N-Bis-(tert-butoxycarbonyl)-2,5-bis-methoxycarbonyl-1,4-dihydropyrazine can be obtained in high yield by treatment of the methyl ester of N-(4-toluenesulfonyl)-N-(tert-butoxycarbonyl)-alpha,beta-didehydroalanine with dimethylaminopyridine and potassium carbonate. This compound was used as substrate in Michael addition reactions with several types of nucleophiles. The electrochemical behaviour of this pyrazine derivative was also studied by cyclic voltammetry and by controlled potential electrolysis.We wish to thank the Fundação para a Ciência e a Tecnologia for financial support (project no. POCTI/1999/QUI/32689)

Detecting abnormalities in endoscopic capsule images using color wavelet features and feed-forward neural networks

This paper presents a system to support medical diagnosis and detection of abnormal lesions by processing endoscopic images. Endoscopic images possess rich information expressed by texture. Texture information can be efficiently extracted from medium scales of the wavelet transform. The set of features proposed in this paper to encode textural information is named color wavelet covariance (CWC). CWC coefficients are based on the covariances of second order textural measures, an optimum subset of them is proposed. The proposed approach is supported by a classifier based on multilayer perceptron network for the characterization of the image regions along the video frames. The whole methodology has been applied on real data containing 6 full endoscopic exams and reached 87% specificity and 97.4% sensitivity.Center Algoritm

Classification of endoscopic capsule images by using color wavelet features, higher order statistics and radial basis functions

This paper presents a system to support medical diagnosis and detection of abnormal lesions by processing capsule endoscopic images. Endoscopic images possess rich information expressed by texture. Texture information can be efficiently extracted from medium scales of the wavelet transform. The set of features proposed in this paper to code textural information is named color wavelet covariance (CWC). CWC coefficients are based on the covariances of second order textural measures, an optimum subset of them is proposed. Third and forth order moments are added to cope with distributions that tend to become non-Gaussian, especially in some pathological cases. The proposed approach is supported by a classifier based on radial basis functions procedure for the characterization of the image regions along the video frames. The whole methodology has been applied on real data containing 6 full endoscopic exams and reached 95% specificity and 93% sensitivity.Centre Algoritm

Synthesis of Dehydrodipeptide and N-ethyl-dehydrodipeptide Derivatives with an α-Aminoisobutyric Acid Residue

Several dipeptides with an N-benzyloxycarbonyl or an N-(tert-butyloxycarbonyl) α-aminoisobutyric acid residue and a β-hydroxyamino acid methyl ester were subjected to dehydration to form dehydrodipeptide derivatives. N-Ethylation of these dipeptides using triethyloxonium tetrafluoroborate with potassium tert-butoxide as auxiliary base led to complex mixtures that failed to render pure products. However, when the 4-nitrophenylsulfonyl protecting group was substituted for the benzyloxycarbonyl or tert-butyloxycarbonyl groups and N,N-diisopropylethylamine was substituted for potassium tert-butoxide, the dehydrodipeptide derivatives were selectively N-alkylated at the amino terminal nitrogen in fair to high yields. Alternatively, N-ethylation can be carried out prior to dehydration. Thus, through a combination of dehydration and N-ethylation procedures, it was possible to obtain dipeptides with α-aminoisobutyric acid and dehydroamino acid residues, which are N-alkylated at the amino terminal nitrogen.Foundation for Science and Technology (FCT) – Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT.info:eu-repo/semantics/publishedVersio

High yielding synthesis of dehydroamino acid and dehydropeptide derivatives

By using a dimethylaminopyridine (DMAP) catalysed reaction of b-hydroxyamino acid derivatives with tert-butylpyrocarbonate [(Boc)2O], dehydroamino acid derivatives are obtained in high yields. The same methodology applied to dipeptides with a b-hydroxyamino acid residue gives the corresponding dipeptides with a dehydroamino acid residue

Michael addition of thiols, carbon nucleophiles and amines to dehydroamino acid and dehydropeptide derivatives

Michael additions of nitrogen heterocycles, thiols, carbon nucleophiles and amines to dehydroalanine derivatives, including a glycyldehydroalanine peptide, were performed in fair to good yields. Dehydroaminobutyric acid derivatives reacted only with the stronger nucleophiles but in considerably lower yields and often no reaction was observed with the corresponding dehydrophenylalanine derivatives. When a tosyl group was bonded to the nitrogen atom of the dehydroamino acid, in some cases the addition product underwent elimination of this group and yielded the corresponding b-substituted derivative of the a,b-dehydroamino acid. Addition of some b- dicarbonyl compounds led to formation of products to which the structure of a,a-disubstituted cyclic amino acid derivatives was assigned