Hydrolytic fragmentation

Hydrolytic fragmentation of the C5-N6 part took place upon heating 7-methyl-5-propyl-2-thioxo-l,2,4-triazolo[l,5-c]pyrimidine (129) with hydrochloric acid. 3-Acetonyl-5-mercapto-l,2,4-triazole (130) and butanoic acid were obtained as a result of N4-C5, C5-N6, and N6-C7 bond cleavages (65JCS3369) (Scheme 50). 

First, we examine the hydrolytic opening of cyclic Mannich bases, i.e., rings that contain N-CH2-0, N-CH2-S, or N-CH2-N fragments. The mechanism of hydrolytic fragmentation of linear Mannich bases was discussed in Sect. 11.5, and, in this section, we demonstrate that cyclic Mannich bases can also be of interest in prodrug design. 

It has already been pointed out (page 346) that the methanolysis of streptomycin yielded, in addition to streptidine, an amorphous, tri-methoxy, basic, disaccharide-like substance which was named methyl streptobiosaminide hydrochloride dimethyl acetal. Acetylation of this material yielded a crystalline tetraacetyl derivative whose composition and molecular weight were in agreement with those expected for the second hydrolytic fragment of streptomycin. ... 

Figure 3. Deuterium exchange-in time courses for C22A-FKBP and a few of its pepsin-catalyzed hydrolytic fragments.

C. amabile yielded echinatine and a new base, amabiline, which differs from cynaustine only in that the basic hydrolytic fragment is (— )-supini-dine 68). 

Hymenocardine (mp 261° [ ]j) — 124°) from this plant was shown to have structure LXX largely because of its acid and alkaline hydrolysis to tryptophan, V-dimethylisoleucylvaline, and p-hydroxy-oi-aminoaceto-phenone. Exhaustive spectral analyses confirmed this structure and aided in the identification of the hydrolytic fragments 109). 

Murase T, Suzuki Y, Doi Y, Iwata T (2002a) Non hydrolytic fragmentation of a poly[(R)-3-hydroxy-butyrate] single crystal revealed by use of a mutant of polyhydroxybutyrate depolymerase. 

Hydrolysis of cyanocobalamin for 5 min with concentrated hydrochloric acid liberated the nucleotide moiety the aminopropanol fragment was retained and there was little effect on either the cyanide group or the amide linkages. This cobalt-containing hydrolytic fragment is identical with Factor B, a microbiologically active compound from fecal material. Further hydrolysis of Factor B yielded corresponding mono-, di-, and tri-carboxylic acids in which the nucleotide moiety was absent. These could also be converted to the parent compound. Factor B, by way of the intermediate mixed anhydride and treatment with ammonia. 

It is completely in line with overlap considerations that only the axial benzoate 202 is isolated from ester hydrolysis. TTie same holds for the hydrolytic fragmentation of acetal 203 [65]. 

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