Deoxy dicarbonyl compound

V. Reactions of 2-Amino-2-deoxy-D-glucose with Dicarbonyl Compounds... 107... 

The reaction of 2-amino-2-deoxy-D-glucose (D-glucosamine) with a dicarbonyl compound was carried out for the first time by Pauly and Ludwig,91 who were trying to discover how pyrrole rings in natural products are formed. They heated free D-glucosamine and ethyl acetoacetate on a steam bath and obtained a substance in which the presence of the pyrrole ring was demonstrated by the pine-splinter test. 

The first two reactions of the sequence are similar to reactions that occur in acidic medium. The 1,2- and 2,3-enediols, and the unsaturated elimination-products derived from them, are present both in acidic and basic solutions. In general, however, reactions in basic solution are much faster than in acidic solution, because of the greater catalytic effect of the hydroxyl ion on the transformation reactions Mechanistic differences between the media become operative in steps c and d. In acid, further dehydration, if it is possible, occurs rapidly, before equilibrium of the deoxy-enediol with the dicarbonyl compound has been established,17 and the products are furans. In alkaline solution, the rapid formation of the tautomeric dicarbonyl compound permits the benzilic acid rearrangement42 to proceed. 

The imidazoles formed in the reaction of aqueous ammonia with other a-hydroxycarbonyl compounds, for example, the triose DL-glyceraldehyde, and such a-dicarbonyl compounds as 3-deoxy-D-glycero-pentosulose (59), and the 3,6-dideoxy-L-erythro-, D-arabino-, and 3-deoxy-D-erytforo-hexosuloses (60, 61, and 62), respectively, are summarized in Table VIII for reactions in which formaldehyde was added, and in Table IX for reactions in which it was not added. 

Another class of pyrrole derivative may be obtained by the interaction of l-amino-l-deoxy-2-ketoses or 2-amino-2-deoxyaldoses with a jQ-dicarbonyl compound. Unlike the previous type (which is N-substituted), these pyrrole derivatives have a tetrahydroxybutyl group in the a- or /8-position with respect to the nitrogen atom of the ring, in addition to other groups arising from the dicarbonyl compound used in the condensation. The formation and reactions of this type of pyrrole derivative have been discussed in detail in two articles in this series48,49 they will, therefore, only be treated briefly. 1-Amino-l-deoxy-D-fructose (53) reacts with 2,4-pentanedione to give50 pyrrole derivative 54a similar pyrroles were obtained with ethyl acetoace-tate,50,51 which yields 54b. 

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

Furanoid analogues such as 261, made from the 5-deoxy-5-iodo- -1 > arabinofuranoside, do not give cyclopentane derivatives by mercury(II) promotion instead 5-mercurated-1,4-dicarbonyl compounds are formed and these do not cyclize.245... 

Pyridines and pyrroles can be formed in different pathways by Mail-lard reaction. The formation of 5-methyl pyrrole aldehyde and 6-methyl-3-pyridinole has been observed by Nyhammar et al (17) by the reaction of isotope labelled 3-deoxyosone with glycine. The 3-deoxy-hexosone represents an -dicarbonyl compound and in this way the Strecker degradation occurs. Another pathway is the reaction of fu-rans with ammonia. Under roast conditions, we have obtained primarily the corresponding pyrrole, whereas we found the corresponding py-... 

The intermediate endiol structures give rise to a facile sugar decomposition by which different aliphatic or cyclic mono- or dicarbonyl compounds are formed. For Amadori rearrangement products two reaction pathways are known the 1-deoxy or the 3-deoxyosone pathways. 

Another important aspect of the Maillard reaction involves the Strecker degradation of ot-amino acids. At elevated temperatures oe-dicarbonyl compounds, such as 3-deoxy glucosone, pyruvaldehyde, glyoxal, and dihydroascorbic acid will cause the degradation of an... 

Another potential side reaction of the enediol(ate) intermediate is formation of the dicarbonyl compound, l-deoxy-D-glycero-2,3-pentodiulose 5-phosphate, resulting from p-elimination of the Cl-phosphate due to improper stabilization and/or premature dissociation of enediol(ate) from the enzyme active site. This compound has been characterized by reduction with borohydride, oxidation with H2O2, complexation with o-phenylenediamine, and 13C-NMR (23, 34). The p-elimination product is not detected in reactions with wild-type R. rubrum Rubisco but is formed in substantial amounts with mutants in which the Cl-phosphate ligands are substituted, demonstrating the required role of these amino acid side chains in stabilizing the enediol(ate) intermediate (34-35). 

In the experiments first described, 2-amino-2-deoxy-D-glucose was heated with an excess of the /3-dicarbonyl compound in the absence of solvent. The product so obtained from ethyl acetoacetate, m.p. 142°, [a]n 49.7°, had an analysis corresponding to that for ethyl 2-methyl-5-(D-ara6mo-tetrahydroxybutyl)pyrrole-3-carboxylate and was considered to have this structure (1). In the reaction with 2,4-pentanedione, a material (m.p. 98°, Md — 25.1°) was obtained which was described as 3-acetyl-2-methyl-5-(D-ara5fno-tetrahydroxybutyl)pyrrole (2). Boyer and Furth" repeated the latter reaction, but in methanol solution, and obtained a product, m.p. 133°, whose analytical data were in agreement with those for structure (2). 

The reactions of amino glycoses with a variety of jS-dicarbonyl compounds have been studied systematically in aqueous acetone solution at neutral pH and room temperature. Under these conditions, well defined products are obtained, sometimes in yields as high as 90-100%. Using this technique, 2-amino-2-deoxy-D-glucose hydrochloride, plus the equivalent amounts of sodium carbonate and ethyl acetoacetate, gives a product (m.p. 142-143°, [a]D —25°) different from that obtained by Pauly and... 

The reaction of 1-amino-l-deoxy-D-fructose with /3-dicarbonyl compounds in aqueous acetone at neutral pH has also been studied. The acetate of this amino sugar affords, with ethyl acetoacetate, ethyl 2-methyl-4-(D-om6wo-tetrahydroxybutyl)pyrrole-3-carboxylate (17). As in previous... 

The reaction of amino sugars with (8-dicarbonyl compounds in alkaline solution produces (tetrahydroxybutyl) pyrroles together with simpler pyrrole compounds lacking the tetrahydroxybutyl side-chain. 2-Amino-2-deoxy-D-glucose hydrochloride and ethyl acetoacetate, heated in aqueous solution at pH 9.7, give a mixture of ethyl 2-methyl-5-(D-ara )mo-tetra-hydroxybutyl)pyrrole-3-carboxylate (1) and ethyl 2-methylpyrrole-3-carboxylate. The yields of these compounds are in the approximate ratio... 

Alkylamino-l-deoxy-D-fructoses (32, R = n-C4H9, CHaCOjCaHs, CHaCeHs) react with the same dicarbonyl compounds giving the corresponding A-alkylpyrroles (33, R = ri-C4H(, (ilHaCOaCsHs, CHaCeHa R = OCaHa, Similarly, 1-arylamino-l-deoxy-D-fructoses (32,... 

Aldol reactions of this type, involving 2-acetamido-2-deoxyaldohexoses, have been studied in connection with the chemical synthesis of A -acetyl-neuraminic acid (50) and related substances, and, for this reason, the choice of the dicarbonyl compound has thus far been limited to oxalacetic acid and its esters. Oxalacetic acid condenses readily with 2-acetamido-2-deoxyaldohexoses in aqueous solution at pH 11. Under these conditions, acetamido sugars partially epimerize, and the aldol reaction takes place for both of the 2-acetamido-2-deoxyaldohexoses present. The complexity of the reaction is further increased by the formation of asymmetric centers at carbon atoms 3 and 4 of the condensation products, namely, diacids (45) and (48), and this can result in the formation of four diastereo-isomers from each sugar. The reaction using 2-acetamido-2-deoxy-o-rnannose (47) has been the one most extensively studied. In this... 

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