Tetrapeptides, oxidation

Tzokova N, Femyhough CM, Butler MF et al (2009) The effect of peo length on the self-assembly of poly(ethylene oxide)-tetrapeptide conjugates prepared by click chemistry. Langmuir 25 11082-11089... 

Ni2 + bound to deprotonated peptide nitrogens in tri- and tetrapeptides can be oxidized to Ni3+ [331-333]. The presence of Ni3+ has been reported in bacterial hydrogenases and dehydrogenases [334, 335], which suggests a biological role for the Ni3 + /Ni2+ redox couple. 

A review on this oxidation state includes some kinetic data. One of the simplest examples is the diamagnetic square planar ion Ag(OH)4, easily prepared in less than millimolar concentrations by electrochemical oxidation of a silver anode in strong base. It is stable for a few hours in 1 M NaOH, and forms orange complexes with tri- and tetrapeptides which resemble... 

Oxidation of the open chain tetrapeptide 62 could afford 63 which on cyclization should immediately lead to ergosecaline (64), a novel type of lactone alkaloid. It was isolated only once from Spanish rye but not sufficiently characterized (89). Hydrolysis of 64 and subsequent decarboxylation would finally give the desired 61. 

Ramstad proposed a ring closure of a linear tetrapeptide to Agurell s compound 67 which could either epimerize irreversibly to the d-proline compound 18 or undergo oxidative ring closure to the peptide alkaloids as also proposed by Agurell. Any of the observations reported... 

Chapter 5 still covers 2-D correlation but has been reorganized, expanded, and updated, which reflects the ever increasing importance of 2-D NMR. The reorganization places all of the spectra together for a given compound and treats each example separately ipsenol, caryophyllene oxide, lactose, and a tetrapeptide. Pulse sequences for most of the experiments are given. The expanded treatment also includes many new 2-D experiments such as ROESY and hybrid experiments such as HMQC-TOCSY. There are many new Student Exercises. 

Coupling of 15 with D-threonine methyl ester in the presence of PyBroP and DMAP gives the dipeptide 73. The oxazole 74 is formed after Dess-Martin oxidation and cyclodehydration with triphenylphosphine/iodine. After formation of the methylamide function, an iterative sequence of deprotection with TBAF and coupling with 15 leads to the dipeptide 75, then to the tripeptide 76 and finally to the tetrapeptide 77. The coupling reagent is PyBroP in each case. The overall yield (74 —> 77) is 21 %. After cata-... 

The phthalimide functional group has absorption and ET properties which make it very attractive in terms of PET processes in which it is the oxidizing species. The application of phthalimide derivatives in carbon-carbon bond forming processes with electron-donating groups such as ethers, thioethers, amines, arenes, carboxylates, etc., has been reviewed. A PET decarboxylation-cycliz-ation sequence has been used for the synthesis of medium-sized (8-16) heterocyclic ring systems (15) from AT-phthaloylanthranilic amides coupled to ca-aminoacids (14). The same PET protocol has been used to convert di-, tri-, and tetrapeptides into cyclopeptides with a minimum of protection and activation... 

Tryptoquivalines appear to be tetrapeptides derived from tryptophan, an-thranilic acid, valine, and alanine (or methylalanine). Deoxynortryptoquivalone (FTN) may be the first metabolite formed in the pathway of tryptoquivaline biosynthesis. Oxidation of the secondary amine to the hydroxyamine would form nortryptoquivalone. If the isobutyl side chain from the above tryptoquivalones is lost by further oxidation, FTJ and FTE would result. On the other hand, if reduction of the carbonyl group following acetylation occurs on the side chain, nortryptoquivaline (FTD) or deoxynortryptoquivaline respectively, would be... 

Compound 636 was converted to 638 under Mitsunohu conditions. Reduction upon heating led to the cyclization product 639. Coupling with a (R)-phenylalanine derivative yielded tetrapeptide 640, which was deprotected to give free diol 641. Diacid 642 was obtained after two consecutive oxidation steps with Dess-Martin periodinane and NaC102. Fmoc-deprotection, DCC-mediated cyclization (—> 643) and benzyl deprotection furnished diketopiperazine enf-WIN 64821 (644). 

The total synthesis of ditryptophenaline (651) used stereoisomer 637, which was oxidized (—> 645) and reduced to give diol 646 (Scheme 10.5). Analogous to the previously described synthesis, 646 was subjected to a Mitsunobu reaction and reduction to furnish cyclization product 647. Benzyl deprotection and coupling with a Fmoc-protected W-methyl-(5)-phenylalanine derivative yielded tetrapeptide 648. TMSE-deprotection, two oxidations (—> 650), Fmoc-deprotection, and DCC-mediated cyclization finally led to the natural product ditryptophenaline (651). 

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