Synthesis of 1,5‐Anhydrohexitol Building Blocks for Oligonucleotide Synthesis

This unit describes in detail, the optimized preparations of 1,5‐anhydrohexitol and the 1,5‐anhydrohexitol building blocks for oligonucleotide synthesis (hG, hA, hC, hT).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143593/1/cpnc0109.pd

Development of pyrimidine- and purine bioisosters

In dieser Arbeit wird die Darstellung einer Gruppe von neuen Purin- und Pyrimidin Bioisosteren diskutiert. Der systematische Name von Purin lautet Imidazo[4,5-d]pyrimidine. Als Nucleosidbausteine finden vor allem die am Imidazolring glycosylierten N9-Purinylnucleoside Anwendung. Beim Einbau in Oligonucleotide wird die klassische Watson-Crick Basenpaarung A-U(T), G-C beobachtet. In dieser Studie wurden am N1 glycosylierte Purinylnucleosidbausteine hergestellt. In dieser am Pyrimidinstickstoff glycosylierten Verbindungsklasse sind neben der klassischen Watson-Crick-Basenpaarung auch weitere Wasserstoffbrückenbindungen zum unsubstituierten Imidazolteil des Nucleosides vorstellbar. Im zweiten Teil wird die Synthese eines neuartigen, flexiblen Purinbioisosters diskutiert, das sich als glycosyliertes Dihetarylamin beschreiben lässt. Dabei werden die charakteristischen Erkennungselemente für sowohl Purine alsauch für Pyrimidine beibehalten. Die Synthese des zugrunde liegenden Dihetarylamins erfolgt entweder durch eine palladiumkatalysierte Aminierungsreaktion oder durch reduktive Entschwefelung des 3-cyclischen Azaphenothiazin Vorläufers.This thesis describes the development of a series of novel pyrimidine- and purine bioisosters. Systematically purines are called imidazo[4,5-d]pyrimidine. In nucleoside chemistry the synthesis and incorporation of N9-purinylnucleoside - glycosylated at the imidazole nitrogen atom is well established. In these cases the classical Watson-Crick base pairing A-U (T), G-C is observed. This study deals with the chemical synthesis of N1-glycosylated purinylnucleoside building blocks. In this substance-class, bearing the sugar moiety at the pyrimidine nitrogen, beside the classical Watson-Crick-base pairing additional hydrogen bridges to the unsubstituted imidazole moiety are conceivable. The second part of this thesis deals with the development and synthesis of a novel, flexible purine bioisoster, which also can be described as a glycosylated dihetaryl amine derivative. In this novel class the typical purine and pyrimidine recognition elements are retained. The proposed dihetaryl amines may either be obtained by palladium catalysed amination reaction or via reductive desulfurination of the 3-cyclic azaphenothiazin precursor

N-Cyclo­pentyl-3-(4-hydr­oxy-6-oxo-1,6-dihydro­pyrimidin-5-yl)-3-p-tolyl­propanamide

In the mol­ecule of the title compound, C19H23N3O3, the six-membered rings are oriented at a dihedral angle of 73.06 (3)°. The cyclo­pentyl ring adopts an envelope conformation. In the crystal structure, inter­molecular N—H⋯O and O—H⋯N hydrogen bonds link the mol­ecules. In the tolyl ring, the H atoms and all but one of the C atoms are disordered over two positions and were refined with occupancies of 0.51 (3) and 0.49 (3)

Halogenated Indole Alkaloids from Marine Invertebrates

This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided

Xenobiotic Nucleic Acid (XNA) synthesis by Phi29 DNA Polymerase

Phi29 DNA polymerase (DNAP) is the replicative enzyme of the Bacillus subtilis bacteriophage Phi29. Its extraordinary processivity and its ability to perform isothermal amplification of DNA are central to many molecular biology applications, including high‐sensitivity detection and large‐scale production of DNA. We present here Phi29 DNAP as an efficient catalyst for the production of various artificial nucleic acids (XNAs) carrying backbone modifications such as 1,5‐anhydrohexitol nucleic acid (HNA), 2′‐deoxy‐2′‐fluoro‐arabinonucleic acid (FANA), and 2′‐fluoro‐2′‐deoxyribonucleic acid (2′‐fluoro‐DNA). A full protocol for the synthesis of HNA polymers by an exonuclease‐deficient variant (D12A) of Phi29 DNAP plus a detailed guide for the design and test of novel XNA synthetase reactions performed by Phi29 DNAP are provided