Photoreactive analogs

Bukhtiyarov, Y.E., Omer, C.A., and Allen, C.M. (1995). Photoreactive analogs of prenyl diphosphates as inhibitors and probes of hnman farnesyltransferase and geranylgeranyl-transferase type I. J Biol Chem 270 19035-19040. 

The phosphonates (50) are photochemically reactive and lead to products dependent upon the nature of the substituents. Irradiation of the phosphonate (50a) yields the product (51a) as a result of a photoreaction analogous to a Norrish Type I process. An analogous product (51b) is also encountered in the photolysis of phosphonate (50b). In this instance however other products (52b) and (53b) are produced as a result of Norrish Type II reactivity and fission of the resultant biradical. Norrish Type II fission dominates the photoreactions of (50c) and (50d) yielding the monoester (52c, d) and the olefin (53c, d). Fission of the C—bond to afford the radical (54) and products derived from it is the result of irradiation of the phosphine (55). ... 

The properties of oilseed rape DGAT have been examined in particulate fractions from MD cultures [1-3]. Recently, photoreactive acyl-CoA analogs have been used to label microsomal acyl-CoA binding proteins from developing soybean cotyledons [4]. The current smdy examines the potential of using photoreactive analogs of acyl-CoA in the characterization of DGAT from MD embryos of oilseed rape. 

Photooxidafions are also iudustriaHy significant. A widely used treatment for removal of thiols from petroleum distillates is air iu the presence of sulfonated phthalocyanines (cobalt or vanadium complexes). Studies of this photoreaction (53) with the analogous ziuc phthalocyanine show a facile photooxidation of thiols, and the rate is enhanced further by cationic surfactants. For the perfume iudustry, rose oxide is produced iu low toimage quantifies by singlet oxygen oxidation of citroneUol (54). Rose bengal is the photosensitizer. 

The acetoxy dienone (218) gives phenol (220). Here, an alternative primary photoreaction competes effectively with the dienone 1,5-bonding expulsion of the lOjS-acetoxy substituent and hydrogen uptake from the solvent (dioxane). In the case of the hydroxy analog (219) the two paths are balanced and products from both processes, phenol (220) and diketone (222), are isolated. In the formation of the spiro compound (222) rupture of the 1,10-bond in the dipolar intermediate (221) predominates over the normal electron transmission in aprotic solvents from the enolate moiety via the three-membered ring to the electron-deficient carbon. While in protic solvents and in 10-methyl compounds this process is inhibited by the protonation of the enolate system in the dipolar intermediate [cf. (202), (203)], proton elimination from the tertiary hydroxy group in (221) could reverse the efficiencies of the two oxygens as electron sources. 

In a related photoreaction, hexafluorobutadiene forms the [2+4] adduct with p (Al.lV-dimethylamino)styrene in 11% yield, whereas no such adduct could be detected for the same reaction with p-methoxystyrene [124] (equation 104) The analogous thermal reaction at 120 °C leads only to [2+2] adducts... 

The [2 + 2] photodimerization of a, j8-unsaturated sulfones is correctly viewed as a photoreaction of alkenes, rather than the sulfone group, and this aspect has been reviewed recently by Reid, as part of a wider survey of the photoreaction of O- and S-heterocycles. The topic continues to attract considerable interest and a few recent examples, as well as some synthetic applications, will be discussed here. Much of the photodimerization work has been carried out on the benzo[fc]thiophene (thianaphthene) 1,1-dioxide system. For example. Porter and coworkers have shown that both 3-carboxybenzo[i]thiophene 1,1-dioxide (65) and its methyl ester give only the head-to-head (hth), anti dimer (66) on irradiation in ethanol. In a rather unusual finding for such systems, the same dimer was obtained on thermal dimerization of 65. Similar findings for a much wider variety of 3-substituted benzo[fi]thiophene 1,1-dioxides have been reported more recently by Geneste and coworkers . In the 2-substituted analogs, the hth dimer is accompanied by some of the head-to-tail (htt), anti dimer. The formation of the major dimer appears to proceed by way of an excited triplet and the regiochemistry observed is in accord with frontier MO theory. 

Analogous intermediates seem to be involved in at least some of the reported photoreactions of related dihydroheteroaromatic systems. On irradiation in benzene, the isoxazolines 181 are converted to benzonitrile (182) and the aldehydes 183 via fragmentation pathways (see Scheme 6)... 

An example of intramolecular addition of an azo group to an alkene has been described 233 irradiation of azoalkene 280 affords an almost quantitative yield of the diazetidine 281 with no competing elimination of nitrogen. An analogous cycloaddition is thought to be implicated in the photoreaction of azobenzene with diketene.234... 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

The photocyclization of cis-diaminomaleonitrile (372) to 4-amino-5-cyanoimidazole (373) has been shown to proceed via the trans isomer 374.308 4-Amino-3-cyanopyrazole does not seem to be an intermediate in this transformation.309 Analogous cyclizations have been reported in the imidazole 373 which undergoes further photoreaction to yield the bicycle 375, and in o-aminobenzonitrile which is converted into indazole.310 This photocyclization has been extended to include enaminonitriles 376 spectroscopic evidence for the intermediacy of iminoketenimes 377 in this311 and other similar transformations312 have been reported. 

Numerous reports of the photoelimination of nitrogen from spiro-3//-pyrazoles have been published.348 The diaza[2,2]spirenes 420 were converted into the benzocyclopropenes 421 by a pathway which has been shown not to involve intermediate indazoles.349 3f/-Indazoles undergo analogous photoreactions.350... 

Intermolecular addition of photochemically generated nitrenes and in particular acylnitrenes to alkenes provides a useful and widely applied route to aziridines.385 An analogous intramolecular photoreaction is thought to be involved in the conversion of the o-azidophenylethylfuran 461 into the pyrrolo[l,2-a]quinoline 462 as outlined in Scheme 13,386 and intramolecular addition to an azo group has been observed in the 8-azido-1-arylazonaphthalenes 463.387... 

In the above cases, the photoreactivity of indole, coumarin, pyridine, and so forth, does not compete effectively with PFR, which becomes the major reaction. However, in the case of the chromene depicted in Scheme 28, the electrocyclic ring opening prevails over PFR. By contrast, the analogous chromane undergoes clearly acyl migration [86]. 

Figures, h CIDNP spectra (cyclopropane resonances) observed during the electron transfer photoreaction of chloranil with c/s-1,2-diphenylcyclopropane (fop) and ben-zonorcaradiene (.bottom). The opposite signal directions observed for analogous protons in the two compounds constitute evidence that the two radical cations belong to two different structure types.

Photolysis (4045-4078 A) of anhydro-5-hydroxy-l,3,2-oxa-thiazolium hydroxide (169, R = Ph) gives benzonitrile (77%), sulfur (> 90%), and carbon dioxide. This reaction has been interpreted as involving the bicyclic intermediate 172, which then transforms via the thiazirin 173 into the thiobenzonitrile oxide 174. The postulated intermediates 172 and 173 are analogous to those proposed (139 and 140) for another photoreaction. The possible involvement of the thionitrile oxide 174 is indicated by its trapping with dimethyl acetylene dicarboxy-late this yields 4,5-dimethoxycarbonyl-3-phenylisothiazole (175). ... 

In contrast to a straightforward and predictable decomposition pattern of photolysis with >400 nm light, irradiation of nitrosamides under nitrogen or helium with a Pyrex filter (>280 nm) is complicated by the formation of oxidized products derived from substrate and solvent, as shown in Table I, such as nitrates XXXIII-XXXV and nitro compound XXXVI, at the expense of the yields of C-nitroso compounds (19,20). Subsequently, it is established that secondary photoreactions occur in which the C-nitroso dimer XIX ( max 280-300 nm) is photolysed to give nitrate XXXIII and N-hexylacetamide in a 1 3 ratio (21). The stoichiometry indicates the disproportionation of C-nitroso monomer XVIII to the redox products. The reaction is believed to occur by a primary photodissociation of XVIII to the C-radical and nitric oxide followed by addition of two nitric oxides on XVIII and rearrangement-decomposition as shown below in analogy... 

Scheme 16.17. Photochemical generation of 50 and 51 from anhydrides 61 and 62. Compound 50 is photocarhonylated to cyclopentadienylideneketene (63). The analogous photoreaction of 57 to ketene 64 was not observed. ...

In all cases studied the E,Z-isomerization has the higher quantum yield, so it is of no importance from which isomer the photoreaction starts. In analogy to the primary product from stilbene the cyclization products from other diaryl olefins will be denoted by DHP. The lifetime of such DHP s can vary from some milliseconds to several hours I2). 

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