The Reaction of Nitriles With Hydrazoic Acid: Synthesis of Monosubstituted Tetrazoles

Mihina, Joseph S.; Herbst, Robert

doi:10.1021/jo01151a027

Cited by 140 publications

(47 citation statements)

References 10 publications

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“…Compounds 1a, 3b, and 3c, the CcO model, (4-((4-azidophenyl) ethynyl)phenyl)methanethiol, and Tris-(benzyltriazolylmethyl)amine (TBTA) were synthesized according to literature procedures (23)(24)(25)(26)(27)(28). The compound 1d was obtained from the Developmental Therapeutics Program Open Chemical Repository at the National Cancer Institute.…”

Section: Methodsmentioning

confidence: 99%

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Barile

Herrmann

Tyvoll

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Platelets are important mediators of blood coagulation that lack nuclei, but contain mitochondria. Although the presence of mitochondria in platelets has long been recognized, platelet mitochondrial function remains largely unaddressed. On the basis of a small amount of literature that suggests platelet mitochondria are functional, we hypothesized that the inhibition of platelet mitochondria disrupts platelet function and platelet-activated blood coagulation. To test this hypothesis, members of the tetrazole, thiazole, and 1,2,3-triazole families of small molecule heterocycles were screened for the ability to inhibit isolated mitochondrial respiration and coagulation of whole blood. The families of heterocycles screened were chosen on the basis of the ability of the heterocycle family to inhibit a biomimetic model of cytochrome c oxidase (CcO). The strength of mitochondrial inhibition correlates with each compound's ability to deter platelet stimulation and platelet-activated blood clotting. These results suggest that for this class of molecules, inhibition of blood coagulation may be occurring through a mechanism involving mitochondrial inhibition. Platelets are directly involved in a number of functions necessary for clotting, including recognition of vascular lesions, triggering activation of the coagulation cascade, and activation of other platelets. The platelet membrane serves as a scaffold for clot formation, and platelets are involved in the activation and cocatalysis of reactions involving many of the soluble clotting factors (1). Like red blood cells, platelets lack nuclei and consequently are unable to replace damaged proteins encoded in the nuclear genome. However, unlike red blood cells, platelets contain actively metabolizing mitochondria (2). Some hints as to the role these mitochondria play in platelet function have been elucidated (3). Along with glycogen granules, platelet mitochondria provide energy that is needed at least indirectly for platelet aggregation and secretion of procoagulant molecules (4). More direct evidence of a role for mitochondria in coagulation rests on observations that changes in the permeability of mitochondrial membranes are linked to changes in coagulation activity (5, 6). These facts imply that inhibition of platelet mitochondrial function should have an inhibitory effect upon platelet-activated blood coagulation.Experimental investigation led to the discovery of three families of small molecule heterocycles that reversibly inhibit mitochondrial respiration and attenuate platelet-activated blood coagulation. These three families of compounds comprise unique examples of a class of anticoagulants proposed to inhibit blood clotting through a mitochondrial mechanism (Fig. 1).The discovery of these particular families of platelet inhibitory molecules occurred after initial work from the Collman laboratory related to biomimetic modeling of cytochrome c oxidase (CcO). CcO is the terminal enzyme in the electron transport chain that catalyzes the four-electron reduction of O 2...

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Section: Methodsmentioning

confidence: 99%

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Barile

Herrmann

Tyvoll

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Initially,t his transformation was achieved by laborious methods using tin or silicon azides or by using strong Lewis acids. [3] As afe,c onvenient, and environmentally friendly procedure was then reported by Sharpless and co-workers. [4] They found that with Zn II salts as Lewis acid catalysts,t his [2+ +3] cycloaddition reaction of azide with nitriles,f or the syntheses of av ariety of 5-substituted 1H-tetrazoles,c an be easily realized in water, an environmentally friendly system.…”

mentioning

confidence: 97%

“…It should be noted that in both cases,s ufficient quantities of NaN 3 were used for complete reaction with terephthalonitrile.T herefore,u nder Lewis acid catalysis (Cd(NO) 3 or Cd(Ac) 2 ), the cycloaddition reaction of terephthalonitrile with NaN 3 proceeds almost completely.Both cyano groups of terephthalonitrile undergo cycloaddition with two molar equivalents of N 3 À ions leading to the generation of the H 2 BDT ligand in situ and the formation of the corresponding coordination polymers,which is consistent with previous reports.…”

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confidence: 99%

Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ Cycloaddition Reaction: An Experimental Approach

et al. 2015

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“…As for the new reaction, subsequent studies showed that transition metal-coordinated azide smoothly and readily undergoes cycloaddition with a great variety of functional and non-functional alkyl and aryl nitriles, much in contrast to organic azides, [24b,161,162] HN 3 , [163] and the free azide ion, [164][165][166] which only react with highly electron-deficient perfluoroalkyl nitriles, cyanoformates and N-alkylated nitriles (nitrilium salts), or require extreme reaction conditions, respectively. Note, however, that the rate of cycloaddition can be greatly enhanced when the azide and nitrile moieties are in the same molecule, or, particularly, when CϵN is attached to a heteroatom (O, S, N) (cf.…”

Section: Complexes With Terminal Azide Ligandsmentioning

confidence: 99%

“…1.6. ), transition metal azides) [164,[302][303][304] -running the reactions in acidic media, [163,164,303,305] in the presence of Lewis acids (BF 3 , AlCl 3 ,. ), [164,306] or with the help of homogeneous and heterogeneous main group and transition metal catalysts as activating agents (e.g.…”

Section: Cleavage Of the Metal-tetrazole Bond: Tetrazole Synthesesmentioning

confidence: 99%

Azide Chemistry – An Inorganic Perspective, Part II^[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems

Fehlhammer

Beck

2015

Zeitschrift anorg allge chemie

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Abstract. In whatever state of bonding -whether covalent to an organic residue or a heteroatom, or polar to ionic in contact with a metal -the azide moiety N 3 is characterized by its high potential of reactivity which essentially manifests itself in two basic processes: the elimination of dinitrogen and the entry into 1,3-dipolar cycloadditions with suitable dipolarophiles, the latter of which clearly predominates the chemistry of azide, also that of its metal compounds. In a preceding review entitled "Part I -Metal Azides: Overview, General Trends and Recent Developments" which was meant to lay the foundations for the present paper, these and other reactions have already been touched upon. The present review -Part II -now focusses in great detail on the formation of five-membered heterocyclestetrazol(at)es, triazol(at)es, triazolin(at)es, thiatriazol(at)es, etc. as well as various consecutive products -from azide and nitriles, isocyanides, alkynes, alkenes and heteroallenes (CS 2 , RN=C=S) in the ligand sphere of the metal. Generally, these [3+2]-cycloadditions are found to CONTENTS

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The Reaction of Nitriles With Hydrazoic Acid: Synthesis of Monosubstituted Tetrazoles

Cited by 140 publications

References 10 publications

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ Cycloaddition Reaction: An Experimental Approach

Azide Chemistry – An Inorganic Perspective, Part II^[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems

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The Reaction of Nitriles With Hydrazoic Acid: Synthesis of Monosubstituted Tetrazoles

Cited by 140 publications

References 10 publications

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration

Uncovering the Role of Metal Catalysis in Tetrazole Formation by an In Situ Cycloaddition Reaction: An Experimental Approach

Azide Chemistry – An Inorganic Perspective, Part II[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems

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Azide Chemistry – An Inorganic Perspective, Part II^[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems