摘要:

Why Pentose‐ and Not Hexose‐Nucleic Acids? Purine‐Purine Pairing in homo‐DNA: Guanine,Isoguanine, 2,6‐Diaminopurine, and XanthineThis paper concludes the series of reports in this journal [1–4] on the chemistry of homo‐DNA, the constitutionally simplifie dmodel system of hexopyranosyl‐(6′ → 4′)‐oligonucleotide systems stidued in our laboratory as potentially natural‐nucleic‐acid alternatives in the context of a chemical aetiology of nucleic‐acid structure. The report describes the synthesis and pairing properties of homo‐DNA oligonucleotides which contain as nucleobases exclusively purines, and gives, together with part III of the series [3], a survey of what we know today about purine‐purine pairingin homo‐DNA. In addition, the paper discusses those aspects of the chemistry of homo‐DNA which, we think, influence the way how some of the structural features of DNA (and RNA) are to be interpreted on a qualitative level.Purine‐purine pairing occurs in the homo‐DNA domain in great variety. Most prominent is a novel tridentateWatson‐Crickpair between guanine and isoguanine, as well as one between 2,6‐diaminopurine and xanthinone, both giving rise to very stable duplexes containing the all‐purine strands in antiparallel orientation. For the guanine‐isoguanine pair, constitutional assignment is based on temperature‐dependent UV and CD spectroscopy of various guanine‐ and isoguanine‐containg duplexes in comparison with duplexes known to be paired in the reverse guanine is replaced by 7‐carbauguanine. Isoguanine and 2,6‐diaminopurine also have the capability of self‐pariring in the reverse‐Hoogsteenmode, as previously observed for adenine and guanine [3]. In this type of pairing, the interchangeably.Fig. 36provides an overall survey of the relative strength of pairing in all possible purine‐purine combinations.Watson‐Crickpairing of isoguanine with guanine demands the former to participate in its 3H‐tautomeric form; hitherto this specific tautomer had not been considered in the pairing chemistry of isoguanine. Whereas (cumulative) purine‐purine pairing in DNA (reverse‐HoogstenorHoogsteen) seems to occur in triplexes and tetrapalexes only, its occurrence in duplexes in a characteristic feature of homo‐DNA chemistry. The occurrence of purine‐purineWatson‐Crickbase pairs is probably a consequence of homo‐DNA'squasi‐linear ladder structure [1][4]. In a double helix, the distance between the two sugar C‐atoms, on which a base pair is anchored, is expected to be constrained by the dimensions of the helix; in a linear duplex, however, there would be no restrictions with regard to base‐pair length. Homo‐DNA's ladder‐like model also allows one to recognize one of the reasons why nucleic‐acid duplexes prefer to pair in antiparallel, rather than parallel strand orientation: in homo‐DNA duplexes, (averaged) backbone and base pair axes are strongly inclined toward one another [4]; the stronger this inclination, the higher the preference for antiparallel strand orientation is expected to be (Fig. 16).In retrospect, homo‐DNA turns out to be one of the first artificial oligonucleotide systems (cf. Footnote 65) to demonstrate in a comprehensive way that informational base pairing involving purines and pyrimidines is not a capability unique to ribofuranosyl systems. Stability and helical shape of pairing complexes are not necessary conditions of one another; it is the potential for extensive conformational cooperativity of hte backbone structure with respect to the constellational demands of base pairing and base stacking that determines whether or nor a given type of base‐carrying backbone structure is an informational pairing system. From the viewpoint of the chemical aetiology of nucleic‐acid structure, which inspired our investigations on hexopyranosyl‐(6′ → 4′)‐oligonucleotide systems in the first place, the work on homo‐DNA is only an extensive model study, because homo‐DNA is not to be considered a potential natural‐nucleic‐acid altenratie. In retrospect, it seems fortunate that the model study was carried out, because without it we could hardly have comprehended the pairing behavior of thepropernucleic‐acid alternatives which we have studied later

ISSN:0018-019X    

DOI:10.1002/hlca.19980810302

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractTo check if the strong inhibition ofN‐acetyl‐β‐D‐glucosaminidase by the tetrazole8and the imidazoles9and10correlates with the presence of a heteroatom corresponding to the glycosidic O‐atom, we prepared the GlcNAc‐derived pyrroles (tetrahydroindolizines)18,19,27,28,34, and35, lacking such a heteroatom. For this. the glucose‐derived pyrroles11–13were treated with aLewisacid in the presence of trimethylsilyl azide. Conditions of kinetic control favored the formation of thegluco‐azides14,23, and30, while thermodynamic control favoured themanno‐azides20,29, and36.Reduction of the azides14,20,23,30, and36by Pd/C‐catalyzed hydrogenolysis or, better, with propanedithiol and Et3N, followed by acetylation or trifluoroacetylation and hydrogenolytic debenzylation, gave the deprotected acetamido‐ and trifluoroacetamido‐pyrroles18,19,22,27,28,34,3540, and41. As compared to the tetrazole8and the imidazole9, the pyrroles18,19,27,28,34, and35are only modest inhibitors ofN‐acetyl‐β‐D‐glucosaminidase from bovine kidney (Kivalues between 10 and 75 μM). indicating the necessity of a heteroatom at the glycosidic position.KiValues between 100 and 160 μM for the inhibition ofN‐acetyl‐β‐D‐glucosaminidase from jack beans were determined for the pyrroles19,34, and35.The trifluoroacetamides inhibited both enzymes about twi

ISSN:0018-019X    

DOI:10.1002/hlca.19980810303

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractThe synthesis of a series of chiral enantiomerically pureC2‐symmetric binucleating ligands is reported. Ligands of type1–4, which consist of a phenolic or heterocyclic unit bridging two chiral dihydrooxazole rings. are readily accessible from chiral amino alcohols. Ligands5aand5bare composed of a cyclic urea or thiourea unit, respectively, and two 3,4‐dihydro‐2H‐pyrrole rings containing a stereogenic center next to theN‐atom. Compounds of this type are readily assembled from ethane‐1,2‐diamine and an imidothioic ester derived from pyroglutamic acid. These new ligands, which can coordinate two metals in close proximity to each other, are of interest regarding possible applications in asymm

ISSN:0018-019X    

DOI:10.1002/hlca.19980810304

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractThe coordination behavior of chiral binucleating ligands of type1–4with various transition metals has been investigated.1H‐NMR Titration experiments with zinc(II) salts gave detailed structural information about the structure of the resulting zinc complexes. Ligand1forms an unusualC3‐symmetric dinuclear zinc complex [Zn2CIL3] (8a) which was characterized by X‐ray crystallography. Treatment of complex8awith various carboxylic acids resulted in ligand‐exchange reactions. With ligand2, a hydroxo‐bridged dinuclear copper complex15was synthesized and its structure elucidated by X‐ray analysis. Solution studies UV and1H‐NMR spectroscopy of the reaction of ligand3with ZnIIand NIIsalts revealed the formation of dimeric species of the type [M2X4L2]. Ligand4formed well‐defined dinuclear complexes with NiIIand CuIIsalts of which the corresponding NiIIcomplex [Ni2(AcO)2(ClO4)2L] (22a) was characterized by crystal

ISSN:0018-019X    

DOI:10.1002/hlca.19980810305

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractBased onO‐methylasparvenone (1), a N‐free 5HT2Cantagonist with moderate affinity (pKi= 6.7), derivatives bearing dimethylamino (7), (dimethylamino)methyl (17,18,21, and22), and aminomethyl substituents (26) in place of the benzylic OH group of1as well as pyrrolidine‐ (33) and piperidine‐fused derivatives (29,43, and45) were synthesized. In contrast to the lead structure1, these new ligands were activein vivoin the rat. The tricycles33and45display high affinities for the 5HT2Creceptor (

ISSN:0018-019X    

DOI:10.1002/hlca.19980810306

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractPirlindole is an antidepressant drug. It acts principally as reversible inhibitor of monoamine oxidase‐A (RIMA) and appears relatively potent in comparison with reference drugs. Pirlindole possesses stereogenic center but is generally used as racemate. In this work, the first preparative resolution of its enantiomeric couple is described. Whereas selective crystallization of salts of chiral acid failed, two asymmetric synthetic pathways were also examined; however, without success. Finally separation and isolation of enantiomers of pirlindole was completed by using the derivatization method coupled with preparative HPLC. Optical purity of each isomer was determined by chiral HPLC. The specific rotation of each antipode was also determine

ISSN:0018-019X    

DOI:10.1002/hlca.19980810307

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractStability constants have been measured for a series of ligands based on a 2,2′‐(pyridine‐2,6‐diyl)bis[1H‐benzimidazole] unit which forms dinuclear double‐stranded helical complexes with copper(I). Variation of different structural parameters confirms the importance of the coordinate bond, the stacking interactions, and the weakly bridging pyridine units observed by X‐ray crystallography. The stabilities of the complexes depend strongly on the solvent, and in MeCN, which is a good solvent for copper(I), the complexes are less stable and assemble in a stepwise manner. The interconversion of the enantiomers may be followed by1H‐NMR and takes place on a millisecond time scale around room temperature. The trends in lability are similar to those found for the stability o

ISSN:0018-019X    

DOI:10.1002/hlca.19980810308

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractThermal reactions of 1,2,3‐trisubstituted aziridines1with 1,3‐thiazole‐5(4H)‐thiones6in toluene yielded, in general, a mixture of two diastereoisomeric spirocyclic [2+3] cycloadducts. The formation of these products can be explained by a stereoselective electrocyclic ring opening of1to give an azomethine ylide2as the reactive intermediate, which is trapped immediately by6viaa stereoselective 1,3‐dipolar cycloaddition. Only in the case oftrans‐dimethyl 1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (trans‐1a), four diastereoisomeric cycloadducts were formed (Scheme 4). This result is rationalized by an isomerization of the intermediate azomethine

ISSN:0018-019X    

DOI:10.1002/hlca.19980810309

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractOligodeoxyribonucleotides containing 7‐deaza‐2′‐deoxy‐8‐methylguanosine (m8c7Gd;2b) were prepared. For this purpose, the phosphonate3aand the phosphoramidite3bwere synthesized and employed in solidphase oligodeoxyribonucleotide synthesis. The structures and the thermodynamic data of duplex formation of oligodeoxyribonucleotides containing2bwere investigated by temperature‐dependent CD and UV spectra and compared with those containing 7‐deaza‐2′‐deoxy‐7‐methylguanosine (m7c7Gd) or 7‐deaza‐2′‐deoxy‐guanosine (c7Gd;2a). In general, compound2breduces the duplex stability. In case of the sequence d(m8c7G‐C)4(18), the B → Z transition was facilitated by the incorporation of2b. Moreover, a single 7‐deaza‐8‐methylguanine residue present in an oligodeoxyribonucleotide tract of guanine residues destabilizes the dG quadruplex significantly. This destabilization is more pronounced than in the case

ISSN:0018-019X    

DOI:10.1002/hlca.19980810310

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY

摘要:

AbstractDue to their small mass, adjacent protons (or H‐atoms) of molecular systems may exhibit quantumentanglement(or quantum correlations), even at ambient conditions. The considerable thermal disturbance and/or manybody interactions of condensed matter and the associateddecoherenceeffect, however, cause this protonic entanglement to be restricted in space and time. Some aspects of entanglement and decoherence are mentioned. Extending our previous theoretical work, in the present paper the focus is on the possible existence of entangled protons belonging to the H‐bonds ofadjacentbase pairs of B‐type DNA. Based on the ‘working hypothesis’ that this effect does really exist, the most probable ‘positions’ for the appearance of protonic entanglement in DNA sequences are qualitatively determined. Furthermore, these ‘positions’ appear to correspond uniquely to dimers of adjacent base pairs of DNA. As a consequence, one can straightforwardly search for an enhanced appearance of such entangled H‐bonds in DNA sequences of living organisms, using the existing DNA databases. A quantitative analysis of protein‐coding DNA sequences of various organisms has been performed, the results of which provide strong evidence for the existence of the considered effect. The most striking finding may be summarized as follows: Quantum entanglement appears preferably between the third base of a codon and the first base of the following one. Quantitative estimates of this and further obtained results are presented. It is also shown that quantum‐chemical considerations of stacking energies cannot account for the results. The new findings provide first evidence for the biological significan

ISSN:0018-019X    

DOI:10.1002/hlca.19980810311

出版商:WILEY‐VCH Verlag GmbH    

年代:1998

数据来源: WILEY