Oxine , synthesis

Ready, J.M., Reisman, S.E., Hirata, M. et al. (2004) A Mild and Efficient Synthesis of Oxin-doles Progress Towards the Synthesis of Welwitindolinone A IsonitrUe. Angewandte Chemie International Edition, 43, 1270-1272. 

Interest in the oxines has for long been intense and in the early years many new oxines were synthesized. Recently Roth and Hofkens1895 have reported the synthesis of a series of N,N,N, N -tetrakis-(8-hydroxy-5-quinolymethyl)-a, w-diaminoalkanes. Examples of their use in the medical sciences are still awaited. 

The more modern style of Skraup synthesis is used to make 8-quinolinol or oxine . ortho-Amino-phenol has only one free position ortho to the amino group and is very nucleophilic, so acrolein can be used in weak acid with only a trace of strong acid. Iron(III) is the oxidant with a bit of boric acid for luck, and the yield is excellent. 

Quinone Oximes.—The most interesting of the derivatives of quinones are the oximes. As stated in the discussion of the ketone structure for quinones one of the proofs for this constitution is the fact that benzoquinone forms both a mono-and a di-oxime when treated with hydroxyl-amine. The mono- oxime of benzoquinone would have the structure as written below and as given on page 638. Now as previously mentioned, (p. 628), para-nitroso phenol, which is made by the action of nitrous acid upon phenol and the constitution of which is established by other methods of synthesis, (p. 627), proves to be one and the same compound with this mono-oxine of para-benzoquinone, the constitution of which is likewise established by the above reaction of hydroxyl amine upon quinone. This is explained by a rearrangement as shown in the following ,... 

Hydroxyquinoline ( oxine ), mp 75°C, contains an intramolecular hydrogen bond and is used as a complexing and precipitating reagent for many metallic ions in analytical chemistry. It is obtained by a Skraup synthesis starting from o-aminophenol. 

A total synthesis of strychnofoline (277), a bisindole constituted from the union of a tetracyclic oxindole and a tryptamine unit, and previously isolated from S. usambarensis (165), has been recently reported (166). A key feature of the synthesis is the convergent assembly of the tetracyclic core containing the oxindole moiety 276 through the ring-expansion reaction of a spiro[cyclopropan-l,3-oxin-dole] 274 and a cyclic imine 275, as shown in Scheme 21. 

A class of zinc ion (Zn2+) sensors, which utilized an unnatural amino acid that included the chelation-sensitive fluorophore, 8-hydroxy-4-(Af,Af-dimethylsulfonamido)-2-methylquinoline (sulfonamido oxine (Sox), Figure 1.3a), provided inspiration for a second class of kinase activity sensors [12-14]. The Sox amino acid was prepared via asymmetric synthesis and converted to the fluorenylmethyloxycarbonyl (Fmoc)-protected derivative and incorporated via SPPS into a peptide containing a proline-mediated fi-turn sequence [13]. The fl-turn was flanked by both Zn-chelating amino acids and the Sox fluorophore (Figure 1.3b). In this case, the fi-turn was included to provide preorganization... 

Walkup, G.K. and Imperiali, B. (1998) Stereoselective synthesis of fluorescent a-amino acids containing oxine (8-hydroxyquinoline) and their peptide incorporation in chemosensors for divalent zinc. /. Org. Chem., 63,... 

Although I do not cover the synthesis of indolines, oxin-doles, isatins, and azaindoles in this monograph, some excellent reviews on the synthesis of these indole analogues are available [241-243],... 

Synthetic thyroxine has been available since 1949 when Hems and his associates [176, 177] succeeded in developing a commercially feasible synthesis of the thyroid hormone. More recently, Meltzer and Stanabeck [178] have developed a more practical synthesis of this hormone. These investigators have incorporated in their synthesis the estabhshed principles of the bios5mthesis of th3n oxine that is, the oxidative coupling of 4-hydroxy-3,5-diiodophenyl-pyruvic acid and 3,5-diiodot5n osine. 

Pinto etal. [52] have reported a consecutive three-component synthesis of oxin-doles that proceeds in the sense of a Sonogashira alkynylation-carbopalladation-CH activation-cyclization sequence, furnishing 3-(diarylmethylene)oxindoles 31 in moderate to good yields (Scheme 12.20). 

Acetamido-4-amino-2,4,6-trideoxy-D-galactopyranosyl precursors such as trichltHoacetimidate 76, were prepared from ethyl 1-thio-a-D-mannopyranoside. Key steps were stereoselective reduction of oxine 74 (available in 5 steps), and azidonitration of glycal 75 (Scheme 23). Their application in the synthesis of disaccharides is covered in Chapter 3. Benzyl 2,4-diacetamido-3-6>-benzyl-2,4,6-trideoxy-P-D-galactopyranoside has been synthesized in 5 steps from benzyl 2-acetamido-3-6>-benzyl-2-deoxy-P-D-galactopyranoside. ... 

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