Hydroxy acids imidazoles

Azolesulfonic acids frequently exist as zwitterions. The usual derivatives are formed, e.g., pyrazole-3-, -4-, and -S-sulfonic acids all give sulfonyl chlorides with PCI5. The sulfonic acid groups can be replaced by nucleophiles under more or less vigorous conditions, e.g., by hydroxy in imidazole-4-sulfonic acids at 170C, and by hydroxy or amino in thiazole-2-sulfonic acids. Benzimidazole-2-sulfonic acids react similarly. 

L-Histidine (2) was converted to (S)-2-hydroxy-3-(imidazol-5-yl)pro-pionic acid (38), with retention of configuration using silver nitrite and orthophosphoric acid. The acid (38) was esterified and the ester (39) treated with 4-nitrobenzenesulfonyl chloride. With the latter treatment, the hydroxyl group was esterified and the N1 atom was sulfonated. Walden inversion of the reaction product (40), using lithium bromide in 2-butan-... 

Large rate accelerations have been observed in the metal ion-promoted hydrolysis of some lactams and these reactions are considered in Section 61.4.10. Other investigations have dealt with divalent metal ion-catalyzed hydrolysis of p-nitrophenyl picolinate in the presence of imidazoles and pyridines having hydroxyl groups in their side chains, the zinc(II)-facilitated hydrolysis of esters of 2-hydroxy acids and the metal ion-promoted hydrolysis of methyl 2-( JV-acetylhydrazono) propanoate. ... 

A variety of specialized reagents have been developed for macrolactonization reactions. Two of the more important are the Corey-Nicolaou reagent, 2,2 -dipyridyl disulfide (232)10 jjjg Mukaiyama reagent, which is 2-chloro-l-methylpyridinium iodide (233). A number of related reagents have been developed, including imidazole disulfide 234 [2,2 -dithio-(4-ferf-butyl-l-isopropylimidazole)]l 2 and imidazole 235 [N-(trimethylsilyl)imidazole].l 3 All of these reagents are effective for the cyclization of co-hydroxy acids, as shown in Table 6.1. For comparison, available cyclization results with DEAD and 234 are included. In this table, a hydroxy acid is converted to a lactone (219). 

A Kolbe cross-coupling electrolysis reaction of 170 with propionic acid (MeOH, Et N, 35 °C) furnishes methyl (iS)-2-hydroxypentanoate which, after protection (TBS-Cl, imidazole, DMF) and saponification (KOH, EtOH), gives the TBS-protected a-hydroxy acid 171 in 58% overall yield [60].This hydroxy acid supplies the 0-1 to C-3 fragment in the convergent synthesis of the antibiotic myxovirescine (172). 

A second system that appeared to differ from the above was found in young leaf tissue by Hitchcock and James (1964) who showed that molecular oxygen, rather than H2O2 was involved (Hitchcoch and Nichols, 1971). Both peanut and leaf systems showed inhibition by imidazole and formed C 2-d-hydroxy acids in addition to C i aldehydes in the absence of added NAD" ". 

Zoledronic acid [(l-hydroxy-2-imidazol-l-yl-phosphonoethyl) phosphonic acid] is a bisphosphonate of the third generation that is in clinical use for the treatment of tumor-induced hypercalcaemia. 

The corresponding hydroxyl compound, 4-hydroxy-5-imidazole-carboxamide, was also synthesized with and injected into rats. No radioactivity appeared in the respiratory CO2, nucleic acid purines, nucleotide purines, or allantoin. Apparently this substance is not active metabolically in purine synthetic reactions. 

Besides the use of stereoselective nitrile-converting enzymes as described above, useful chiral building blocks have also been obtained by stereoselective nitrile-forming enzymes. The main product class of nitrile-forming enzymes are cyanohydrins (a-hydroxynitriles, 1-cyanoalkanols), which are versatile synthons in organic synthesis that are readily convertible to a-hydroxy acids [90], a-hydroxy aldehydes [91], ethanolamines [92], amino alcohols, pyrethroid insecticides [93], imidazoles, and heterocycles [94]. Examples of valuable bioactive products derived from chiral cyanohydrins are (i )-adrenaline, L-ephedrin, and (5)-amphetamines [95]. For the synthesis of chiral cyanohydrins, stereoselective enzymes from both plant and bacterial sources have been used. 

Naphtho[l, 2-c]furazans electrophilic reactions, 6, 410 synthesis, 6, 418 Naphtho[l, 2-c]furoxans eleetrophilic reactions, 6, 410 3-Naphthoic acid, 2-hydroxy-l-(2-thiazolylazo)-analytical uses, 6, 328 Naphtho[ 1,2-h]imidazoles oxidation, 5, 405... 

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