Deamination, nitrous acid

Goldberg and Wydler have shown that the 17a-ketone is not the only product of the Tiffeneau ring enlargement sequence. Careful examination of the products derived from nitrous acid deamination of 17a-aminomethyl-5a-androstane-3/l,17j6-diol 3-acetate (91) showed the presence of a minor amount of isomeric D-homo-17-one (98). 

In 1967, Heidelberger, Stacey et al. reported the purification, some structural features, and the chemical modification of the capsular polysaccharide from Pneumococcus Type I. Difficulties of direct hydrolysis of the polysaccharide were overcome and it was possible to identify some of the fragments in the hy-drolyzate. At least six products resulted from nitrous acid deamination. Two were disaccharides, which were identified, and sequences of linked sugar units were proposed. As modification of the polysaccharide decreased the amounts of antibody precipitated by anti-pneumococcal Type I sera, the importance of the unmodified structural features in contributing to the specificity of the polysaccharide was indicated. 

Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%)." In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

Both positional linkages (uronic acid to hexosamine and hexosamine to uronic acid) were established as being (1 — 4) by structural analysis of the previously mentioned (see Section IV), crystalline disaccharides containing D-glucuronic acid, isolated from an acid hydrolyzate of carboxyl-reduced heparin.128-129 Further evidence was obtained from the structure of the D-glucuronic acid-containing counterpart of disaccharides 6 and 8, obtained as minor products from pig-mucosal heparin following nitrous acid deamination,1110 136-138 and acid hydrolysis followed by N-acetylation,130 respectively. 

Scheme 2. — Nitrous Acid Deamination of 2-Amino-2-deoxy-D-glucose and Its Glycosides.

The nitrous acid deamination of 2-amino-2-deoxy-D-mannose (12), in which the amino group is axially attached in the most favored con-... 

The chemistry of the 2,5-anhydrides of aldoses subsequently entered a prolonged lull, and Peat s review21 of 1946 in this Series does not report on any work later than 1925. The experimental basis of the deamination of amino sugars with nitrous acid was, nevertheless, established. The progress afterwards made in the conformational analysis of sugars made it possible for Shafizadeh22 to draw a parallel with the nitrous acid deamination of the aminocyclohexanols, and to rationalize the whole of these results. 

The nitrous acid deamination of 2-amino-2-deoxy-D-mannose (8), in the favored conformation, the amino group ofwhich is axially attached, leads, in contrast, uniquely to D-glucose,15 characterized, after oxidation by nitric acid, as D-glucaric acid (9). This result has also been verified by direct crystallization of the D-glucose and by assay with D-glucose oxidase.44"... 

As might be expected, the nitrous acid deamination of methyl 2-amino-4,6-0-benzylidene-2-deoxy-a-D-altropyranoside (10) hydrochloride leads45,46 uniquely to methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside (11). The benzylidene group does not play an... 

In attempting to obtain 2,5-anhydro-D-glucose diethyl dithioacetal, Defaye58 performed the nitrous acid deamination of 2-amino-2-deoxy-D-glucose diethyl dithioacetal (27) under weakly acidic conditions (acetic acid and sodium nitrite), and obtained a principal product later shown59 to be ethyl 2-S-ethyl-l,2-dithio-a-D-mannofuranoside (28). Shortly before, Horton and coworkers60 had reported the forma-... 

CBH2(CH3XC3H5)(N02)3 mw 210.19, N 13.33% vel crysts. mp 48-5°. Prepd by mixed acid nitration at —10° of 2-acetanilido-4-ethyltoluene, return to the free amine [yel-bm plates (benz), mp 186°], and nitrous acid deamination... 

Nitrous acid deaminations have been invaluable in the investigation of the structure of heparin.85,236-253 The potential value of de-... 

Treatment of NAD+ with nitrous acid deaminates the adenine ring. The resulting deamino NAD+ as well as synthetic analogs containing the following groups in place of the carboxyamide have been used... 

A more striking example of the influence of conformation on the reaction outcome is seen in the nitrous acid deamination of 2-aminocyclohexanols which takes place by rearrangement of a group on the carbinol carbon that is anti to the developing carbocation. The deamination reaction is very fast and the products reflect the population of the chair conformers. The trans isomer exists mainly in the diequatorial conformer thus the only group anti to the amino... 

The carbohydrate sequence of the major tetrasaccharlde was determined by examining the nitrous acid deamination products (25) as permethylated disaccharides by chemical ionization mode of gas chromatography/mass spectrometry. The products were identified as hexosyl-2,5-anhydromannitol and hexosyl-myoinositol,indicating that the major tetrasaccharide had the sequence Galp(l->4)GlcNAcp(l->4)Glcp(l- -2)Inos (Figure 5). 

The carbonium ion rearrangements become much more synthetically useful when cation stabilizing substituents are present. Nitrous acid deamination of 2-aminoadamantan-l-ol 75) gives 4-protoadamantanone in 92 % yield 76). Similarly, deamination of 2-aminoadamantane-l,3-diol 77> gives 8-hydroxy-4-protoadamantanone in 56 % yield (Eq. (20)) 78). Hydrolysis of l-methyl-2-... 

D. Horton and K. D. Philips, The nitrous acid deamination of glycosides and acetates of 2-amino-2-deoxy-D-glucose, Carbohydr. Res., 30 (1973) 367-374. 

T. Elbert, M. Cerny, and J. Defaye, Nitrous acid deamination of conformationally inverted aminodeoxyhexopyranoses, Carbohydr. Res., 76 (1979) 109-119. 

The final step in the synthesis—replacement of the amino group in XI by a hydroxyl group—was carried out by Posternak28 by treatment with nitrous acid. Inversion occurred, giving a 10-15% yield of myo-inositol the other products of the reaction could not be identified. A much better yield (71 %) was achieved by the nitrous acid deamination of the penta-acetate ester of XI, rather than by deamination of the free inosamine.30,31 This method has been utilized30,31 for the preparation of myo-inositol- -C14 from nitromethane-C 14. 

The nitrous acid deamination of sc /ZZo-inosaminc (CXXIII) and myo-inosamine-2 (CXXII),28 as well as that of neo-inosamine-2 (see above), has been studied. Much reducing material is formed from CXXII and CXXIII, and the deoxyinosose CXX has been demonstrated28 among the deamination... 

The products obtained in the nitrous acid deamination of amine 117 in acetic acid are shown in Scheme 10 (Nishimura et ol., 1967, 1970). Nitrogen loss occurs from a primary saturated carbon atom and this case is therefore not strictly pertinent to this section. To account for the formation of ketone 118 among the reaction products the authors... 

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