Diazoacetyl compounds

The reaction with carboxylates occurs over a range of pH values, but is optimal at pH 5. Unfortunately the diazoalkyl compounds will cross-react with sulfhydryl groups at this pH. Under higher pH conditions, the reaction is even less specific due to reaction with other nucleophiles. In aqueous solution, the most likely side reaction is hydrolysis. 

Carbodiimides are used to mediate the formation of amide or phosphoramidate linkages between a carboxylate and an amine or a phosphate and an amine, respectively (Hoare and Koshland, 1966 Chu etal., 1986 Ghosh etal., 1990). Regardless of the type of carbodiimide, the reaction proceeds by the formation of an intermediate o-acylisourea that is highly reactive and short-lived in aqueous environments. The attack of an amine nucleophile on the carbonyl group of this ester results in the loss an isourea derivative and formation of an amide bond (see Reactions 11 and 12). The major competing reaction in water is hydrolysis. 

Diazomethane and other diazoalkyl derivatives long have been used to label carboxylate groups for analysis (Herriott, 1947 Riehm and Scheraga, 1965). A major application of such 

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Ghatak and co-workers49 have reported further progress on their synthetic elaboration of the atisane system, as outlined in Scheme 5. A key step in the synthesis of the tetracyclic compound (162) was the CuO-catalysed inter-molecular alkylation of the diazoacetyl compound (163). 

The syntheses of diazoacetyl compounds have been described ( 5.8.2). Because pf their potential utility, the synthesis of an ethyl diazomalonyl derivative and an aryl azide precursor of carbenes and nitrenes, respectively, are presented below. 

Diazoacetyl compounds s. a. a-Diazoketones 3-Diazoacetyl-d 5-pyrazoline ring... 

Franich et have found that aromatic amines cannot be converted to the diazoacetyl compound via the 4-nitrophenyl ester or via the car-... 

There are two catalytically active residues in pepsin Asp-32 and Asp-215. Their ionizations are seen in the pH-activity profile, which has an optimum at pH 2 to 3, and which depends upon the acidic form of a group of pKa 4.5 and the basic form of a group of pKa 1.1.160,161 The pKa values have been assigned from the reactions of irreversible inhibitors that are designed to react specifically with ionized or un-ionized carboxyl groups. Diazo compounds—such as A-diazoacetyl-L-phenylalanine methyl ester, which reacts with un-ionized carboxyls—react specifically with Asp-215 up to pH 5 or so (equation 16.28).162-164 Epoxides, which react specifically with ionized carboxyls, modify Asp-32 (equation 16.29). 

Optical induction emanating from a chiral diazoacetamide is apparently not much higher. The 2-phenylcyclopropanecarboxylates cis-222 and trans-222, obtained in low yield from (N-diazoacetyl)oxazolidones 220,221 and styrene in the presence of Rh2(OAe)4 followed by ethanolysis, showed only small enantiomeric excesses 215). Starting with either diazo compound, the (1/ ) enantiomer was predominant in both cis- and trans-222. 

The diazo compound 0-(2-diazoacetyl)-L-serine, known also as azaserine (see Fig. 22-48), is a powerful inhibitor of glutamine amidotransferases. If growing cells are treated with azaserine, what intermediates of nucleotide biosynthesis would accumulate Explain. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

Carbenes, which may be formed photochemically from precursors such as diazo compounds and diazirines, are highly reactive entities containing divalent carbon. The first photogenerated reagent was a carbene, formed by irradiation of diazoacetyl chymotrypsin (Singh et al., 1962). 

Protease Classification. In order to rationally design an inhibitor for a protease it is first necessary to place it into one of four families of proteases (see Table V). For a new enzyme, a study of its inhibition profile with a series of general protease inhibitors is sufficient to classify it into one of the four families. The inhibitors usually used are diiso-propylphosphofluoridate (DFP) or phenylmethane sulfonyl fluoride (PMSF) for serine proteases, 1,10-phenanthroline for metalloproteases, thiol reagents such as iodoacetate or N-ethylmaleimide for thiol proteases, and pepstatin or diazo compounds such as diazoacetyl-norleucine methyl ester for carboxyl proteases. 

Acetylphenyl butyl tellurium is formylated at the acetyl-methyl group by methyl formate and sodium in diethyl ether. The formyl compound is converted to butyl 2-(diazoacetyl)-phenyl tellurium upon treatment with 4-methylbenzenesulfonyl azide1. The diazoacetyl group is converted to the dibromoacetyl group by bromine in diethyl ether1. 

Derivatives of fentanyl and sufentanil with chemo- and photoaffinity functionalities attached to the anilido nitrogen (e.g., NCOCH2Br, NCOCH=N2) have been reported, but affinity labeling experiments performed with theses compounds on brain tissue met with little success. Some of the compounds, notably the diazoacetyl analog of cis 3-methylfentanyl, displayed high binding affinities.(60)... 

This compound is a severe skin irritant, hence great care should be exercised to avoid any contact. For best yields in the rearrangement step this crystallization is recommended, since I he yield of ethyl 1-naphthylacetate is reduced by about 20% if the crude product is used in the rearrangement. A sample of crystallized l-(diazoacetyl)naphthalene, m.p. 52-53°, that had been stored in a screw-top bottle in a refrigerator for about 2 weeks afforded the same yield of ethyl 1-naphthylacetate as a freshly prepared sample. 

Thermolysis of 2-(diazoacetyl)cyclobutanones 338 furnishes 5-spirocyclo-propyl-A -butenolides via intermediate a-ketenylcyclobutanones. The method is acceptable for the synthesis of various spiropolycyclic compounds 340, 341 in moderate to high yields (91JOC1453). Diazo compound 342 was pyrolyzed (350°C/0.1 mm) to give 343 in 40% yield (86TL2447). 

Carbenes, generated by photolysis of di- and tetrachloro-o-quinone diazides, react with oxetane in a 1 3 ratio to afford 15-membered crown ethers. Benzocrown ether 675 was obtained in 16% yield (91CB1865). Derivatives of macrocyclic crown ethers with four or five oxygen atoms in a ring were synthesized by Cu(acac)2-catalyzed cyclization of a,polyethylene glycols. 20-26-Membered crown-4(5) ethers 676 were prepared from the above-mentioned diazo ketones with tri- or tetra-ethylene glycols in 7-26% yields. Treatment of l,8-bis(diazoacetyl)octane with dodecane-l,12-diol under the same conditions results in a mixture of 52-membered tetraether 646 (40%) and compound 645 (81CC616). 

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