Thiazole Fragment Research Articles

Benzothiazolium-π-thiazole-dicyanomethanides: new nonlinear optical chromophores

A series of merocyanines with a benzothiazolylidene donor and a quinoidal thiazole moiety have been synthesized. Experimental results and theoretical calculations show that these compounds have zwitterionic ground states and negative second-order optical nonlinearities. Unlike most merocyanines, the degree of charge transfer does not decrease on increasing the separation between the donor and the acceptor groups, an unexpected feature related to the presence of the proaromatic thiazole fragment.

6,7]‐Heterocycle‐Fused 14‐Hydroxymorphinan Derivatives: Design, Synthesis, and Opioid Receptor Activity

A series of new 14-hydroxymorphinan analogues with a thiazole or imidazo[2,1-b]thiazole fragment as the heterocyclic function fused to ring C were designed and synthesized. These compounds can be viewed as the result of a direct modification at ring C of the 14-hydroxymorphinan scaffold. Among these compounds, three were identified as having potent binding affinity (approximately 1 nM) at both kappa and mu receptors, and acting as agonists at kappa and partial agonists or antagonists at mu receptors. In view of the promising results from studies on compounds with mixed kappa and mu receptor activities, these new compounds warrant further investigation.

Cover Picture: Facile, One-Step Production of Niacin (Vitamin B3) and Other Nitrogen-Containing Pharmaceutical Chemicals with a Single-Site Heterogeneous Catalyst (Chem. Eur. J. 8/2008)

Single-Site Catalytic green production of Niacin is reported by R. Raja, J. M. Thomas et al. on page 2340 ff. The compound, which is used for the preparation of Vitamin B3, is obtained in a single-step, solvent-free, and environmentally benign manner with a solid source of active oxygen. Reducing Agents In his Concepts article on page 2310 ff., C. Chatgilialoglu describes the flexibility and applicability of (Me3Si)3SiH in several synthetic transformations, such as radical reductions, consecutive radical reactions, and hydrosilylation.1 Antibiotic Thiazolylpeptides In their Full Paper on page 2322 ff., T. Bach et al. describe the synthesis of the potent antibiotic thiazolylpeptide GE2270 A using a modular assembly of the individual thiazole fragments to the pyridine core to yield the compound in 4.8 % over 20 steps. 1 Polyoxometalate Hybrid Assemblies In their Full Paper on page 2349 ff., L. Cronin et al. describe the design of polyoxometalate nanoscale hybrid assemblies comprising a core shell hydrophilic–hydrophobic structure. The synthesis has been achieved by covalently tethering alkyl chains (C6, C16 and C18) to a Mn-Anderson cluster core producing a surface-grafted cluster architecture.1

Construction of macrocyclic thiodepsipeptides: synthesis of a nosiheptide ‘southern hemisphere’ model system

A 20-membered macrocyclic thiodepsipeptide has been synthesized as a model for the southern hemisphere of nosiheptide, the key steps being assembly of an acyclic precursor by amide coupling of indole and thiazole fragments followed by formation of the thiolactone in the macrocyclization step.

Discovery and SAR of Potent, Orally Available and Brain‐Penetrable 5,6‐Dihydro‐4H‐3‐thia‐1‐aza‐benzo[e]azulen‐ and 4,5‐Dihydro‐6‐oxa‐3‐thia‐1‐aza‐benzo[e]azulen Derivatives as Neuropeptide Y Y5 Receptor Antagonists.

Combination of structural elements from a potent Y5 antagonist (2) with thiazole fragments that exhibit weak Y5 affinities followed by lead optimisation led to the discovery of (5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino and (4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino derivatives. Both classes of compounds are capable of delivering potent and selective orally and centrally bioavailable NPY Y5 receptor antagonists.

Discovery and SAR of potent, orally available and brain-penetrable 5,6-dihydro-4H-3-thia-1-aza-benzo6e9azulen- and 4,5-dihydro-6-oxa-3-thia-1-aza-benzo6e9azulen derivatives as neuropeptide Y Y5 receptor antagonists

Combination of structural elements from a potent Y5 antagonist (2) with thiazole fragments that exhibit weak Y5 affinities followed by lead optimisation led to the discovery of (5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino and (4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-piperidin-4-ylmethyl-amino derivatives. Both classes of compounds are capable of delivering potent and selective orally and centrally bioavailable NPY Y5 receptor antagonists.

Discovery and SAR of potent, orally available and brain-penetrable 5,6-dihydro-4 H-3-thia-1-aza-benzo[ e]azulen- and 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[ e]azulen derivatives as neuropeptide Y Y5 receptor antagonists

Combination of structural elements from a potent Y5 antagonist ( 2) with thiazole fragments that exhibit weak Y5 affinities followed by lead optimisation led to the discovery of (5,6-dihydro-4 H-3-thia-1-aza-benzo[ e]azulen-2-yl)-piperidin-4-ylmethyl-amino and (4,5-dihydro-6-oxa-3-thia-1-aza-benzo[ e]azulen-2-yl)-piperidin-4-ylmethyl-amino derivatives. Both classes of compounds are capable of delivering potent and selective orally and centrally bioavailable NPY Y5 receptor antagonists.

New laser media based on bifluorophore coumarin molecules

The effect of heterocycles of different types on the fluorescence and generation properties of ten new bifluorophores is investigated experimentally. It is shown that a number of 7-diethylaminocoumarins with a triazole cycle or an oxydiazole cycle are characterized by the highest generation efficiency in the region of 500–515 nm. The maximum generation energy was 2.5 J in lamp pumping, which exceeds widely known coumarin 334 in efficiency by a factor of 1.7. Stabilization of the coumarin fragment by the nucleus of julolidine—7-N(CH2)6—has a favorable effect on the photostability of these molecules. The effect and the role of the isomer form of the thiazole fragment on the spectral and generation properties of the molecule are established. A favorable effect on the generation efficiency of the imino group in the coumarin fragment of the molecule is shown.

A Formal Total Synthesis of Epothilone A: Enantioselective Preparation of the C1−C6 and C7−C12 Fragments1

Our continued interest in the anticancer agent paclitaxel is driven by the desire to understand the structural features and spatial arrangement necessary for tubulin binding2 and stabilization of microtubule dynamics.3 The recently reported class of natural products, epothilone, now provides us with compounds structurally distinct from taxol and taxol analogues but with similar biological activity. In addition, epothilones have much greater activity against multi-drug resistant cell lines.4 After independently determining the relative stereochemistry of epothilone A we reported our synthetic approach, Figure 1, which includes a late-stage macrocyclic olefin metathesis.5 Our initial publication presented an enantioselective preparation of thiazole fragment C and the successful application of a ring-closing olefin metathesis reaction to an epothilone model system. Concurrently, three other synthetic groups reported similar approaches to epothilone A all of which have culminated in total synthesis.6-10 Herein we report the details of our independent, enantioselective preparation of the ketone fragment B and aldehyde A. Ketone B has been prepared from a sequence which is highlighted by a samarium-mediated Reformatsky reaction11 originally developed by Molander, Scheme 1. The sequence begins with racemic alcohol 2 readily prepared in one step from propionaldehyde and 3-methyl-2-butenylmagnesium chloride. Enzymatic resolution in methyl tert-butyl ether using Altus Biologics12 Chiro-CLECPC(which is reusable without significant loss of activity) provided an efficient route to gram quantities of (R)-2 after purification and deacylation. The enantioselectivity of the resolution at 47% conversion was determined to be >20:1 by Mosher ester methodology13 and chiral capillary gas chromatography (see Experimental Section for details). The enantiomeric excess was found to be dependent upon percent conversion (97% ee at 15% conversion and 92% ee at 48% conversion). The unreacted alcohol 2 can be easily recycled by a two-step oxidationreduction sequence. Acylation of the secondary hydroxyl occurred readily with bromoacetyl bromide in the presence of N,N-dimethylaniline to provide ester 3 in excellent yield. Ozonolytic cleavage of the terminal olefin yielded the necessary Reformatsky precursor which under exposure to freshly prepared SmI2 provided the lactone 4 in quantitative yield with >20:1 diastereose-

Total synthesis of nosiheptide. Synthesis of thiazole fragments

AbstractThe preparation of three new thiazole derivatives from natural products is described, as well as improvements in the synthesis of ethyl 2‐aminomethyl‐4‐thiazolecarboxylate.

Histamine H2antagonists: powerful ligands for copper(II). Reinterpretation of the famotidine–copper(II) system

Potentiometric, absorption, EPR and 13C NMR spectroscopic studies performed for a series of effective H2 antagonists of histamine (imidazole-4-ethanamine) including effective antiulcer drug famotidine, have shown that all ligands containing a guanidine–thiazole fragment co-ordinate copper(II) ions at pH around 2 using two nitrogen donors. The guanidine moiety having acidic nitrogen (log K 1.5–3.0) acts as an anchor and the thiazole nitrogens with protonation constants around pK 6.7 very efficiently form a chelate ring. The adjacent thioether sulfur may also be involved in metal-ion binding, contributing to the stabilities of the complexes formed. At higher pH an amine terminal fragment is involved in co-ordination via one of its nitrogens leading to a {N,N,S,N} binding set. Comparison of all results obtained for the seven compounds studied strongly suggests that only equimolar species can be detected in this system. This allows a convincing reinterpretation of earlier studies on the copper(II)–famotidine system.

Negative ion fragmentations of deprotonated heterocycles. The isothiazole, thiazole, isoxazole, and oxazole ring systems

The major collision-induced dissociations of deprotonated isothiazole occur from the 5-anion, while deprotonated thiazole fragments almost equally through the 2- and 5-anions. Both 5-anions fragment by a simple retro cleavage yielding HC 2S − and HCN. The 5-anion of isothiazole and the 2-anion of thiazole also rearrange to the common intermediate −SCHCHCN which decomposes by losses of H 2, HCN and H 2S. There is no evidence for direct interconversion of isothiazole and thiazole anions. The spectra of deprotonated methylisothiazoles are complex, but the major fragmentations are of ring deprotonated ions and are generally analogous to the parent systems. The fragmentation behaviour of deprotonated isoxazole and oxazole is analogous to that of the isothiazole and thiazole systems.

Cultural and biochemical characteristics of a leptospire from frog kidney.

Growth of a leptospire isolated from frog kidney tissue was stimulated by the addition of glucose to a bovine albumin polysorbate 80 medium, did not grow in the absence of polysorbate 80, but did respire on a complex of polysorbate 80 and bovine albumin. Growth was completely inhibited by 2-deoxy-D-glucose in a glucose-free bovine albumin polysorbate 80 medium. A requirement for vitamins B1 (thiamine) and B12 was demonstrated. Oxythiamine and the thiazole fragment of thiamine were nearly equivalent to vitamin B1 in growth supporting activity while thyamine pyrophosphate, thyamine monophosphate, the pyrimidine fragment of vitamin B1 and pyrithiamine were much less effective. The isolate was continually propagated at 31.5, 29, 20, 15, and 9 C. Growth could be initiated at 33.5–34 C. but serial subculture failed. Growth was not initiated at 35 u.c. The organism had a cellular but no extracellular tributyrinase.

A New Synthesis of the Thiazole Fragment of Vitamin B11

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA New Synthesis of the Thiazole Fragment of Vitamin B11Thomas E. Londergan, Norman L. Hause, and William R. SchmitzCite this: J. Am. Chem. Soc. 1953, 75, 18, 4456–4458Publication Date (Print):September 1, 1953Publication History Published online1 May 2002Published inissue 1 September 1953https://doi.org/10.1021/ja01114a018RIGHTS & PERMISSIONSArticle Views803Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (401 KB) Get e-Alerts Get e-Alerts