Synthesis of acetogenin analogues. Asymmetric transfer hydrogenation coupled with dynamic kinetic resolution of α-amido-β-keto Ester

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Atsetogeniinid on huvitav grupp looduslikke ühendeid, millel on leitud selektiivne tsütotoksilisus vähirakkude vastu. Kuigi atsetogeniine on juba mõnda aega uuritud, ei ole nende struktuuri ja bioloogilise toime suhe veel selge. Oluline on uurida ka atsetogeniinide sünteesimisvõimalusi, panustades nii nende erinevate struktuuride paremale kättesaadavusele, kuna taimeekstraktid sisaldavad atsetogeniine vähestes kogustes ja tihti mitut erinevat atsetogeniini struktuuri korraga. Antud uurimistöös sünteesiti kuus atsetogeniini analoogi ja hinnati nende bioloogilist toimet mudelvähirakuliinil. Väljatöötatud sünteesirada saab kohandada igale sünteesitud analoogile, mis erinevad üksteisest ühe keskse ühiku poolest. Seega saab analoogi erinevad struktuurielemendid eraldi valmis sünteesida ja lõpp-ühendiks kokku panna alles viimastes etappides. Sünteesi juures pöörati erilist tähelepanu aatomite ruumilisele asetusele struktuuris ehk stereokeemiale, millel on tihti väga oluline mõju ühendi bioloogilisele toimele. Neli ühte tüüpi analoogi mõjutasid rakukasvu üksteisega võrreldaval määral, kuigi ei viinud nii palju mudelvähirakke rakusurmani kui looduslikud atsetogeniinid; kaks teist tüüpi analoogi avaldasid rakukasvule vähem mõju. Uurimistöö teine osa käsitleb võrreldes esimese teemaga suhteliselt väikeste ühendite, aminohappe derivaatide, sünteesi. Selliseid ühendeid saab edukalt kasutada keerukamate molekulide sünteesil. Töös keskenduti aminohappe derivaatide sünteesivõimalusele asümmeetrilise vesiniku ülekande teel läbi dünaamilise kineetilise lahutamise, mis andis kõrgeid saagiseid. Reaktsiooni käigus liideti aminohappe derivaadi eellasele üks vesiniku aatom kõrge stereoselektiivsusega. Vesiniku aatom pärines ühelt teiselt reaktsioonis osalevalt orgaaniliselt ühendilt, mitte gaasiliselt vesinikult nagu sarnaste reaktsioonide puhul tihti kasutatakse. Leitud meetod võimaldab reaktsiooni läbi viia toatemperatuuril ja õhukeskkonnas, vältides gaasilise vesiniku ja kõrgete rõhkude kasutamist.Acetogenins are an interesting group of natural compounds, which can exhibit selective cytotoxicity towards tumorous cell-tissue. Although acetogenins have been studied for a while now, the relationship between their structure and bioactivity has not been fully elucidated. In this work six analogues of acetogenins were synthesized and their bioactivity was assessed in a model tumorous cell line. The developed synthetic route can be adjusted for all of the analogues synthesized – this approach allows units of the compound to be prepared separately, and joined together in later stages to form the end-compound. The spatial arrangement of the atoms in the structure, called stereochemistry, was also under scrutiny during the synthesis. The three-dimensional positioning within the structure can often be very important for the bioactivity. Four of the synthesized analogues, similar in type, retained bioactivity in model tumour cells causing cell death, although being less active than their natural counterparts. Two other synthesized analogues exhibited negligible bioactivity in the tested cell-line. The second part of the presented work discusses the synthesis of amino acid like derivates. These relatively small, yet important molecules can be used as ‘building blocks’ in the synthesis of more complex molecules. The study entailed the synthesis of these derivates via asymmetric transfer of a hydrogen atom coupled with dynamic kinetic resolution, giving high yields. During the reaction one hydrogen atom was added to the starting material with high stereoselectivity, noting that the hydrogen atom originated from another organic compound in the reaction mixture and not from hydrogen gas. The developed method permits the reaction to be run at room temperature and in air atmosphere, omitting the use of high pressures and hydrogen gas, often used for similar transformations

PENGARUH KUALITAS PRODUK DAN HARGA TERHADAP MINAT BELI KONSUMEN PADA QUBICLE COFFEE PALEMBANG

Penelitian ini bertujuan untuk mengetahui pengaruh kualitas produk dan harga terhadap minat beli konusmen pada Qubicle Coffee Palembang baik secara parsial maupun simultan. Analisis data dilakukan dengan metode regresi linear berganda yang diolah dengan menggunakan aplikasi SPSS versi 22 for windows. Data dikumpulkan dengan menggunakan kuesioner. Teknik pengambilan sampel pada penelitian ini menggunakan metode non probability sampling yaitu teknik accidental sampling, sehingga didapatkan sampel pada penelitian ini sebanyak 37 responden yaitu konsumen pada Qubicle Coffee Palembang. Berdasarkan hasil penelitian analisis koefisien determinasi (R2) besarnya pengaruh kualitas produk dan harga terhadap minat beli konsumen adalah sebanyak 53,8% dan sisanya sebesar 46,2% dipengaruhi oleh hal lainnya yang tidak dibahas dalam penelitian ini. Berdasarkan hasil uji t secara parsial kualitas produk berpengaruh secara positif terhadap minat beli konsumen, sedangkan secara parsial harga berpengaruh secara positif terhadap minat beli konsumen. Berdasarkan hasil uji F secara simultan kualitas produk dan harga secara signifikan berpengaruh terhadap minat beli konsumen pada Qubicle Coffee Palembang

O-GlcNAcase contributes to cognitive function in Drosophila

Contains fulltext : 219183.pdf (publisher's version ) (Open Access

Discovery of a wide companion near the deuterium burning mass limit in the Upper Scorpius association

We present the discovery of a companion near the deuterium burning mass limit located at a very wide distance, at an angular separation of 4.6+/-0.1 arcsec (projected distance of ~ 670 AU) from UScoCTIO108, a brown dwarf of the very young Upper Scorpius association. Optical and near-infrared photometry and spectroscopy confirm the cool nature of both objects, with spectral types of M7 and M9.5, respectively, and that they are bona fide members of the association, showing low gravity and features of youth. Their masses, estimated from the comparison of their bolometric luminosities and theoretical models for the age range of the association, are 60+/-20 and 14^{+2}_{-8} MJup, respectively. The existence of this object around a brown dwarf at this wide orbit suggests that the companion is unlikely to have formed in a disk based on current planet formation models. Because this system is rather weakly bound, they did not probably form through dynamical ejection of stellar embryos.Comment: 10 pages, including 4 figures and 2 table

Characterization of a piezoelectric acoustic sensor fabricated for low-frequency applications: a comparative study of three methods

Piezoelectric transducers are widely used for generating acoustic energy, and choosing the right radiating element is crucial for efficient energy conversion. In recent decades, numerous studies have been conducted to characterize ceramics based on their elastic, dielectric, and electromechanical properties, which have improved our understanding of their vibrational behavior and aided in the manufacturing of piezoelectric transducers for ultrasonic applications. However, most of these studies have focused on the characterization of ceramics and transducers using electrical impedance to obtain resonance and anti-resonance frequencies. Few studies have explored other important quantities such as acoustic sensitivity using the direct comparison method. In this work, we present a comprehensive study that covers the design, manufacturing, and experimental validation of a small-sized, easy-to-assemble piezoelectric acoustic sensor for low-frequency applications, using a soft ceramic PIC255 from PI Ceramic with a diameter of 10 mm and a thickness of 5 mm. We present two methods, analytical and numerical, for sensor design, followed by experimental validation, allowing for a direct comparison of measurements with simulated results. This work provides a useful evaluation and characterization tool for future applications of ultrasonic measurement systems.This workwas supported by the grants PID2020-116329GB-C22 and TED2021-129336B-I00 funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR. This work is also a result of an internship funded by the Autonomous Community of the Región of Murcia through the Fundación Séneca—Agencia de Ciencia y Tecnología de la Región de Murcia (Seneca Foundation—Agency for Science and Technology in the Region of Murcia) and the European Union’s NextGenerationEU program