Muscone is a precious fragrant compound, which is scarce in nature, many synthetic attempts for this unique natural product have been carried out. A new synthetic method for 2,15-hexadecanedione, a precursor of muscone, from imidazalium salt and di-Grignard reagent is reported. Imidazalium salt was used as tetrahydrofolate coenzyme model at formic acid oxidation level and di-Grignard reagent as nucleophile to which one-carbon unit was transferred, the biomimetic synthesis of 2,15-hexadecanedione was successfully accomplished by using the addition-hydrolysis reaction of imidazolium salt with di-Grignard reagent. A novel method for preparing muscone is provided.
Na busca por novos inibidores de protease aspartica, conjugados de ferroceno com estatina foram planejados e sintetizados através de reação de aclopamento usando o protocolo padrão N,N'-diciclohexilcarboimida (DCC) e 1-hidroxibenzotrizol (HOBt). Os novos compostos foram caracterizados por espectroscopia de IR, 1 H NMR, MS e análise elementar. Os resultados do bioensaio mostraram que alguns dos novos compostos podem servir como ponto de partida.In a search for new aspartic protease inhibitors, conjugates of ferrocene with statine were designed and synthesized by coupling reaction using the standard N,N'-dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) protocol. The title compounds were characterized by IR, 1 H NMR spectroscopy, MS and elemental analysis. The results of bioassay showed that some title compounds could serve as a starting point.Keywords: statine, ferrocene, aspartic protease, synthesis, biological activity
IntroductionAspartic proteases are involved in many biological pathways in fungi, plants, humans, parasites, retroviruses.
1-2Aspergillus oryzae aspartic proteinase is found to have activity not only for the activation of trypsinogen but also for the activation of chimotrypsinogen with the cleavage of the Arg15-Ile16 bond.3 Statine, the (3S, 4S)-4-amino-3-hydroxy-6-methylheptanoic acid configurational isomer is a key component of pepstatin and of other synthetic peptide inhibitors of aspartic protease. 4 It is well known that long-chain peptides can exhibit poor penetration and are generally unsuitable for a metabolically stable drug, because of enzymatic degradation.5 In many case, this inconvenience can be circumvented by shortening the length of the inhibitors.Ferrocene is a member of a special organometallic group known as metallocenes or "sandwich" molecules. Among metallocenes there are compounds with antiproliferative effect, antibiotics, and inhibitors of enzymes.6-9 Conjugates of ferrocene with well-known drugs were reported.
10-11Ferrocene-containing compounds often possess unexpected biological activity. 12 We report here the search for shorter aspartic protease inhibitors resulting from introducing ferrocenyl unit into statine and synthesized the novel statine derivatives which might provide interesting biological properties. The structure of target compounds is listed in Table 1.
Experimental
Materials and equipmentAll the reactions were carried out under a nitrogen atmosphere with the exclusion of moisture. All the amino acids used were L-amino acids. N-Boc-statine and N-Boc-AHPPA were synthesized according to the method described in the literature. 13 Ferrocenylmethylamine was synthesized by the literature method of Kelly et al.14 For syntheses of compounds 4 and 10 see reference.15 Solvents were purified and dried by standard methods. The melting points were determined on an XT-4 micro melting point apparatus and uncorrected. IR spectra were recorded on an EQUINOX-55 spectrometer on a KBr matrix.1 H NMR spectra were recorded on an INOVA-400 NMR spectrometer using T...
An efficient synthetic approach to the synthesis of ferrocenyl heterocyclic derivatives in dilute solutions has been developed. The new compounds were characterised by means of IR, UV, and 1 H NMR, spectroscopy and elemental analysis. The structure of complex I was studied by X-ray single-crystal diffraction. The synthesized compounds have a potential of new enzyme models and molecular recognition hosts.
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