Mechanism of thermal decomposition of diazirine. Evidence for diazomethane intermediate

Jennings, Barry M.; Liu, Michael T. H.

doi:10.1021/ja00436a073

Cited by 29 publications

(14 citation statements)

References 3 publications

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“…Complete rearrangement of 1 in MeOH can be excluded, as the disappearance of the UV absorption at 350 nm during thermolysis is of first order (cf. [93]). …”

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confidence: 99%

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Vasella

Witzig

Waldraff

et al. 1993

Helvetica Chimica Acta

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Dedicated to Duilio Arigoni on the occasion of his 65th birthday (1.X.93)In the context of the hypothesis postulating a heterolytic cleavage of a C-N bond during thermolysis of alkoxydiazirines (Scheme I ) , we report the preparation of the diazirines4,5,7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4,5,7, and 8 (Schemes 2-5) were prepared from the known hemiacetals 10,19,34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11,20,35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together wlth the cyclic hydroxylamine 44. Oxidation of 11,35, and 43 (N-chlorosuccinimide/l,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO,) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)-and (2)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu,. Treatment of the hydroximolactone 0-sulfonates 13,23,37, and 46 with NH,/MeOH afforded the diaziridines 15,25,38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51,16/17,26/27,52/53,39/40,48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C-N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23" led mostly to the diastereoisoineric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal59 was obtained in higher yields (IS%), together with 44% of 5658, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of4 in toluene, THF, or dioxane and of 9 in CH2C12 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.Introduction. -Diazirines [I] are important precursors of carbenes, and the mechanism of their thermolysis attracted considerable attention, which focused on the concertedness of the cleavage of the two C-N bonds and the homo-or heterolytic nature of the bond breaking [2-71. The mechanism and the kinetics of the thermolysis of (a1koxy)alkyldiazirines (see [8] and earlier papers of the series [9-131) have not been studied, but we hypothesized that thermolysis of 1-azisugars, such as 1, i.e. cyclic (alkoxy)alkyldiazirines, is initiated by heterolysis of one of the C( 1)-N bonds, accord-

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“…Complete rearrangement of 1 in MeOH can be excluded, as the disappearance of the UV absorption at 350 nm during thermolysis is of first order (cf. [93]). …”

mentioning

confidence: 99%

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Vasella

Witzig

Waldraff

et al. 1993

Helvetica Chimica Acta

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“…The average concentration of hSERT used in these studies was 267 +/-1 µg/mL. Cholesterol has been shown to interact with membrane proteins and alter their function (37)(38)(39)(40)(41). as well as assist in the formation of lipid rafts (41,42).…”

Section: Resultsmentioning

confidence: 99%

“…1). Irradiation of this analog produces reactive carbene intermediates that form stable adducts with neighboring lipid or protein (37,38). Given the location of the carbene, it is expected that the cholesterol will label proteins at the top and bottom of the acyl chain region of the bilayer, close to the interfacial headgroup region.…”

Section: Resultsmentioning

confidence: 99%

Characterizing the lipid-protein interface of the human serotonin transporter by crosslinking mass spectrometry

DeMarco

Ferraro

Sweigard

et al. 2020

Preprint

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Altered serotonin (5-HT) levels contribute to disease states such as depression and anxiety. Synaptic serotonin concentration is partially regulated by the serotonin transporter (SERT), making this transporter an important therapeutic target. This study seeks to examine the lipid accessible domains of hSERT to provide critical information regarding the apo-state of this transporter in a lipid environment. Recombinant hSERT was inducibly expressed in a human cell line. Solubilized SERT was purified by affinity chromatography using a FLAG Tag and reconstituted into mixed lipid vesicles containing our photoactivatable lipid probe. The lipidaccessible domains of the reconstituted transporter in membranes in its apo-state were probed via photocrosslinking to azi-cholesterol followed by quadrupole time of flight liquid chromatography-mass spectrometry (QTOF-LC-MS). MS studies identified crosslinks in three transmembrane loops consistent with the known topology of SERT. Surprisingly, the amino-and carboxy-terminal domains were similarly crosslinked by cholesterol, suggesting that these regions may also be intimately associated with the lipid bilayer. The data presented herein assist in further refining our understanding of the topography of the apo-state of hSERT via analysis of lipid accessibility. INTRODUCTION:

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“…26 However, in a manner similar to the alkyl counterparts 1b these materials are difficult to synthesise (unless the aryl group is phenyl) and less stable than diazirines derived from ketones. Arylalkyl diazirines 27,28 (see 1g and 5 in Fig. 1) were found to behave in a similar manner to their dialkyl analogues 1a and undergo intramolecular rearrangement to afford styrenic species which are able to react with the carbene to afford cyclopropanes 6.…”

Section: Development Of Diazirinesmentioning

confidence: 96%

Development and application of diazirines in biological and synthetic macromolecular systems

2005

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Many different reagents and methodologies have been utilised for the modification of synthetic and biological macromolecular systems. In addition, an area of intense research at present is the construction of hybrid biosynthetic polymers, comprised of biologically active species immobilised or complexed with synthetic polymers. One of the most useful and widely applicable techniques available for functionalisation of macromolecular systems involves indiscriminate carbene insertion processes. The highly reactive and non-specific nature of carbenes has enabled a multitude of macromolecular structures to be functionalised without the need for specialised reagents or additives. The use of diazirines as stable carbene precursors has increased dramatically over the past twenty years and these reagents are fast becoming the most popular photophors for photoaffinity labelling and biological applications in which covalent modification of macromolecular structures is the basis to understanding structure-activity relationships. This review reports the synthesis and application of a diverse range of diazirines in macromolecular systems.

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Mechanism of thermal decomposition of diazirine. Evidence for diazomethane intermediate

Cited by 29 publications

References 3 publications

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Glycosylidene Carbenes. Part 13. Synthesis and thermolysis of representative 1‐azi‐glycoses

Characterizing the lipid-protein interface of the human serotonin transporter by crosslinking mass spectrometry

Development and application of diazirines in biological and synthetic macromolecular systems

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