Diazo compounds diazoacetyl

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. 

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). 

Does the preparation react with the ligand analog in the dark during the time required for a typical photolysis During prolonged pho-tolyses, e.g., diazo compounds at 350 nm, a diazoacetyl derivative may label the receptor in a dark reaction by an electrophilic mechanism. Analysis of such incubation mixtures also tests for removal of noncova-lently bound material in the work-up procedure. 

Renin can be inactivated more readily by aliphatic diazo compounds such as diazoacetyl-DL-norleucine methyl ester or diazoacelylglycine methyl ester in the presence of cupric ion. These reagents are soluble in water and hence do not require organic solvents. However, the reaction is less selective, since these latter reagents can react with other acid proteases. 

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). 

Another common feature of the amidotransferases is that they are inhibited by the antibiotics azaserine (0-diazoacetyl-L-serine) and 6-diazo-5-oxo-L-norleucine when glutamine is substrate. However, these compounds are much less inhibitory when NH3 is the nitrogen donor. Recently two new glutamine analogues have been introduced, 2-amino-4-oxo-5-chloro-pentanoic acid 2) and albizziin 8). The structures of these compounds are given in Fig. 5-3. 

Related Reagents, Compound (1) can be converted to reagents that undergo further transformation to a variety of diazo carbonyl compounds. Succinimidyl diazoacetate (24) is easily obtained by the reaction of TV-hydro xysuccinimide with compound (1) is a stable, easily stored solid that is highly selective toward diazoacetyl transfer to amines and phenols (eq 16). ... 

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