A new method for the preparation of tetrazoles from nitriles using trimethylsilylazide/trimethylaluminum

Huff, Bret E.; Staszak, Michael A.

doi:10.1016/s0040-4039(00)61437-5

Cited by 114 publications

(29 citation statements)

References 16 publications

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“…Interestingly, the conversion of all three azide anions of Al(N 3 ) 3 to afford aluminum tetrazolate has not been described to date. [64] In these reactions, trimethylsilyl azide (TMSN 3 ) served as the azide donor. They postulated that Lewis acids should activate the nitrile group towards reaction with azide ions.…”

Section: Methods Using Lewis Acidsmentioning

confidence: 99%

Synthesis and Functionalization of 5‐Substituted Tetrazoles

2012

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Tetrazoles are synthetic heterocycles with numerous applications in organic chemistry, coordination chemistry, the photographic industry, explosives, and, in particular, medicinal chemistry. In organic chemistry, 5‐substituted tetrazoles are used as advantageous intermediates in the synthesis of other heterocycles and as activators in oligonucleotide synthesis. In drug design, 5‐monosubstituted tetrazoles are the most important tetrazole derivatives because they represent non‐classical bioisosteres of carboxylic acids, with similar acidities but higher lipophilicities and metabolic resistance. In this review we focus on the preparation and further functionalization of these heterocycles. Firstly, the role of 5‐substituted tetrazoles in medicinal chemistry is described, including examples of their effects on pharmacokinetics, pharmacodynamics, and metabolism of the associated drugs. Then, the main synthetic approaches to 5‐substituted tetrazoles – consisting of methods based on acidic media/proton catalysis, Lewis acids, and organometallic or organosilicon azides – are presented, from the early procedures to the most recent ones, with special attention paid to the reaction mechanisms. Functionalization of 5‐substituted tetrazoles is a challenging task because it usually leads to the formation of two isomers, 1,5‐ and 2,5‐disubstituted tetrazoles, in various ratios. In this overview, reactions with high or unusual regioselectivities are described, with comments on the possible mechanisms. Microwave‐assisted approaches to the synthesis and functionalization of 5‐substituted tetrazoles are also included.

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Section: Methods Using Lewis Acidsmentioning

confidence: 99%

Synthesis and Functionalization of 5‐Substituted Tetrazoles

2012

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“…Thus, treatment of 20 with Zn(CN) 2 [46]. To form the tetrazole ring, the 2-carbonitrile 48 was subjected to a 1,3-dipolar cycloaddition with in situ prepared Al(N 3 ) 3 [47]. This yielded 76% of the tetrazolyl derivative 49 9 ), which was debenzylated (BCl 3 ) to afford the tetrazolylimidazopyridine 50 (85%).…”

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confidence: 99%

“…± The C(2)-substituted imidazopyridines 9 ± 13, 28,29,32,35,40,41,43,46,47, and 50, and the 2,3-unsubstituted imidazopyridine 8 were tested as inhibitors of b-mannosidase from snail (acetate buffer, 258, pH 4.5) and amannosidase from Jack beans (acetate buffer ZnCl 2 , 378, pH 4.5), with the corresponding 4-nitrophenyl mannosides as substrates. The inhibition data for the bmannosidase ± K i (in some cases IC 50 ) and K i /K M ± and the pK values for those mannoand gluco-imidazopyridines that possess the same substituents at C(2) are compiled in Table 1, while the data for the inhibition of this b-mannosidase by the other mannoimidazopyridines are listed in Table 2.…”

mentioning

confidence: 99%

Synthesis of C(2)‐Substituted manno‐Configured Tetrahydroimidazopyridines and Their Evaluation as Inhibitors of Snail β‐Mannosidase

Terinek

Vasella

2003

Helvetica Chimica Acta

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It was shown that retaining b-glucosidases and galactosidases of families 1 ± 3 feature a strong interaction between C(2)OH of the substrate and the catalytic nucleophile. An analogous interaction can hardly take place for retaining b-mannosidases. A structureÀactivity comparison between the inhibition of the b-glucosidase from Caldocellum saccharolyticum (family 1) and b-glucosidase from sweet almonds by the gluco-imidazoles 1 ± 6, and the inhibition of snail b-mannosidase by the corresponding manno-imidazoles 8 ± 13 does not show any significant difference, suggesting that also the mechanisms of action of these glycosidases do not differ significantly. For this comparison, we synthesized and tested the manno-imidazoles 9 ± 13, 28, 29, 32, 35, 40, 41, 43, 46, 47, and 50. Among these, the alkene 29 is the strongest known inhibitor of snail b-mannosidase (K i 6 nm, non-competitive); the aniline 35 is the strongest competitive inhibitor (K i 8 nm).Introduction. ± The strong inhibition of b-glucosidases by imidazoles of type 1 [1 ± 3] has been rationalized by the similarity of shape of the inhibitor and of the putative reactive intermediate, an oxycarbenium cation, and by the cooperative interaction of the imidazole with the catalytic nucleophile and acid [4]. A correlation between the inhibition constant and the pK value of the C(2)-and C(3)-acetamido imidazoles 7 and 14 ± 16, and by related azoles has established that substituents at C(3) lower the inhibitory activity [5]. The structureÀactivity relation (SAR) resulting from varying the C(2)-substituents has been studied in detail [6]. It was shown that the HOCH 2 group at C(2) in 2, and particularly the flexible hydrophobic PhCH 2 CH 2 group in 3 lead to an improved inhibition, with K i values as low as 0.1 nm (against Caldocellum saccharolyticum b-glucosidase) 1 ). The C(2)-substituents affect both the strength and the type of the inhibition (competitive or mixed, with a varying between 2.5 and 15).Legler and Withers evidenced that the C(2)OH group of b-glucosides and bgalactosides interacts with the catalytic nucleophile of the retaining b-glucosidases and b-galactosidases of families 1 [8], 2 [9], and 3 [10] [11]. 2-Deoxy-and 2-deoxy-2-fluorob-d-glucosides and -galactosides are cleaved much less readily than the parent substrates, the rate-determining step being deglycosylation of the enzyme. The transition state for this reaction is considered very similar to that of the enzyme glycosylation [9], and the most important interaction in the transition state was considered with the C(2)OH 2 ). That 2-deoxyglucosides are cleaved less readily than the parent substrates is surprising, as the OH group at C(2) is known to destabilize an

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“…21 This provided furanyl tetrazole 12 after careful workup with a Na 2 HPO 4 /H 3 PO 4 buffer solution (pH = 2.1). 22 The overall yield of 12 from 9 was 33% (Scheme 1). A mixture of regioisomeric N -methyl tetrazoles 16 , which are unable to ionize via proton transfer, were prepared as controls.…”

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confidence: 99%

Tailored fragments of roseophilin selectively antagonize Mcl-1 in vitro

Bracken

Carlson

Frederich

et al. 2015

Tetrahedron Letters

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We have discovered a fragment of the natural product roseophilin, a member of the prodiginine family, that antagonizes Mcl-1 functions in a liposome-based assay for mitochondrial membrane permeabilization. By tailoring this substance such that it can participate in salt bridging with the protein surface, we have prepared the first prodiginine inspired structure that shows direct, saturable binding to a recombinant Bcl-2 family member in vitro.

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A new method for the preparation of tetrazoles from nitriles using trimethylsilylazide/trimethylaluminum

Cited by 114 publications

References 16 publications

Synthesis and Functionalization of 5‐Substituted Tetrazoles

Synthesis and Functionalization of 5‐Substituted Tetrazoles

Synthesis of C(2)‐Substituted manno‐Configured Tetrahydroimidazopyridines and Their Evaluation as Inhibitors of Snail β‐Mannosidase

Tailored fragments of roseophilin selectively antagonize Mcl-1 in vitro

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