Sydnones derivative

The compound 7-(4-chloro-benzyl)-2-(4-chloro-phenyl)-3,8a-dihydro-pyridazino[4,3-( ][l,3,4] thiadiazin-8-one 42 has been reported to be active against Bacillus Escherchia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by a serial dilution method <2001IJB475>. Triazino-thiadiazines 24f, 25b, 25c, and 25f <2002IJH287> have been reported to be active against S. aureus-, sydnone derivatives of triazino-thiadiazine 24f <2002IJH287> are more reactive than coumarin derivatives. 

The following activities have been claimed for sydnone derivatives (26) antibacterial, antitumor, antifungal, anti-... 

In some cases mesoionic systems have proved to be valuable precursors for 1,2,3-triazoles bearing latent functionalities. Thus, the oxatriazole derivative (314) decompsoes to an intermediate azide, which can be intercepted, e.g. by tolane, forming triazole (315) (68CB536). In a related photoreaction, the sydnone derivative (316) gives a 2/7-1,2,3-triazole (31 by way of an intermediate nitrilimine (317). The reaction mechanism has been studied by N-labelling ( ) (78HCA1477). 

Sydnones were the first mesoionic molecules subjected to detailed study, and are named after the University of Sydney where they were first prepared by Earl and Mackney in 1935. Sydnones are generally prepared by dehydrative cyclization of N-nitrosamino acids, which are synthesized by N nitrosation of amino acids [6]. Sydnone derivatives have been extensively studied for... 

The antitumor effect of SYD-1 might be related to the enzyme-linked function of mitochondria, since it has been shown to depress the efficiency of electron transport and oxidative phosphorylation [11]. Thus, SYD-1 is now one of the most attractive compounds among sydnone derivatives which show antitumor activity. 

Fig. 11 a Bicyclononyne-containing proteins can be labeled with sydnone derivatives and vice versa, b Sydnone-containing proteins can be labeled with bicyclononyne derivatives... 

PROBLEM 23.39 Reaction of A -phenylalanine (1) with nitrous acid affords A -nitroso amino acid (2), which on treatment with acetic anhydride yields sydnone (3). Sydnones belong to a class of compounds known as mesoionic compounds. These compounds cannot be satisfactorily represented by Lewis structures not involving charge separation. The name sydnone derives from the University of Sydney where the first examples were prepared in 1935. Reaction of 3 and dimethyl acetylenedicarboxylate (DMAD) gives pyrazole (4). Propose mechanisms for the formations of 2, 3, and 4. Hint. For the formation of 4, it may be helpful to consider the other possible Lewis structures for sydnone 3. 

Included among the various antimalarlal compounds synthesized >dilch show activity in mice are 6,8-disubstituted pyrido [2,3-b] pyrazines, mono- and di-sydnone derivatives of DDS, 9 90 3 phenylrhodanines,91... 

Pertluoroallene is also quite reactive in its additions to nitrones [20], diazoalkanes [20] and sydnones [19] With sydnones, the isolated product derives from a fluoride ion rearrangement of the primary adduct (equation 21)... 

Alkoxy)alkynylcarbene complexes have been shown to react with nitrones to give dihydroisoxazole derivatives [47]. Masked 1,3-dipoles such as 1,3-thia-zolium-4-olates also react with alkynylcarbene complexes to yield thiophene derivatives. The initial cycloadducts formed in this reaction are not isolated and they evolve by elimination of isocyanate to give the final products [48]. The analogous reaction with munchnones or sydnones as synthetic equivalents of... 

Die Reduzierbarkeit meso-ionischer Verbindungen mit Hydriden ist ebenfalls struk-turabhangig. Sydnone werden z. B. durch Natriumboranat nicht angegriffen1 1,3-Thia-zon-(4)-Derivate reagieren dagegen unter Bildung von 4-Oxo-1,3-thiazolidinen2. 

The mass spectra of compounds 1-14 have been discussed in CHEC-II(1996) <1996CHEC-II(8)733>. The mass spectra of all the new reported compounds displayed the corresponding molecular ions consistent with their respective molecular formulas. The mass spectra of the derivatives 17a (R1 = Ph, R2 = H) and 17b (R1=Ph, Rz = OMe) showed fragment peaks due to loss of (M-NO-CO), characteristic of sydnone-containing molecules, at m/z = 346 and 376, respectively <2002IJH287>. The other significant peaks were observed at m/z =187 and 217 due to the formation of 3-aryM-cyanosydnone. Similarly, in the mass spectrum of 25 <2002IJH287>, the peak at 324 was due to the loss of C02 from molecular ion and the peak at mlz = 171 was due to the formation of 3-cyanocoumarin. The molecular ion peak of the compound 24 (R1 =/-Bu, R2 = H) was observed at m/z = 368. 

Molecular ions were observed by gas chromatography-mass spectrometry (GC-MS) analysis for trifluoroacetyl 58 and trimethylsilyl 60 derivatives of mesocarb (sydnocarb) 59 (Section 5.03.12) <1999JMP1079>. Unlike the silyl derivative 60 and sydnones <1996CHEC-II(4)165>, no [M+—NO] ion was observed for trifluoroacetyl derivative 58. The characteristic ions PhCH2(Me)CH+ (m/z 119) and PhCH2+ (tn/z 91) were observed for both derivatives 58 and 60. 

Phenylsydnone 89 is not restricted to [3+2] cycloaddition. Reaction of sydnone 89 and its derivatives with the substituted azete 90 gives isomeric l//-triazepines after extrusion of carbon dioxide (Equation 8). 

Alkynyl-substituted sydnones 106 are prepared from the new trimethylsilylethynyl derivative 105. 4-Cuprio-3-phenylsydnone 104 <1996CHEC-II(4)165> reacts with l-bromo-2-trimethylsilyl acetylene to give product 105,... 

Synthesis of the first mesoionic nematic and smectic A liquid crystals derived from sydnones has been described and their self-organization into liquid crystal phases has been studied by optical, calorimetric, and powder X-ray diffraction methods <2005CC1552>. 

Some mesoionic heterocycles, structurally correlated to the sydnones and represented by a general 5-membered ring molecule that contains the NO-moiety, behave as NO-donors. They include sydnonimines 81 and mesoionic 1,2,3,4-oxatriazolium derivatives 82 and 83. The latter will be named 3-R-l,2,3,4-oxatriazolium-5-olates (82) and S-R-l S -oxatriazolium-S-Rj-amenates (83) [77]. 

Among the NO-donor mesoinoic heterocycles, the sydnonimines have attracted by far the most interest. They were first obtained by Brookes et al. [78] and Kato et al. [79] by the action of nitrous fumes on a-( N-rnelh yl-N-riilrosoamino)-nitriles followed by the action of acetic anhydride. Whereas sydnones represent a family of stable heterocycles, sydnonimines, with the exception of 3-hydroxysydnonimine (81, R=OH, Ri =H) that forms an inner salt [80], are unstable if not protonated to a salt or acylated to stable N-acylimino derivatives. In this case they can be stored at room temperature... 

The final products derived from 1 1 addition of sydnones to alkenes are usually pyrazoles or dihydropyrazoles. The pyrazoles are formed by oxidation of intermediate dihydropyrazoles. An unusual example of aromatization by elimination of an alkane (toluene) in prefence to hydrogen is illustrated in Scheme 7 <89TL4625>. 

The nitrosoimine derivative RE 2047 (45) in combination with pentoxifylline demonstrates potent antithrombotic activity <95AP(328)71). Other sydnones with pharmacological activity include derivatives of the general formulas (46) and (47). These agents were shown to have antiinflammatory, analgesic, and antipyretic activity <95JPS263). 3-Arylsydnones have been intensively studied because... 

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