Biomimetic Synthesis Of Muscone And Long-chain Diketones

The tetrahydrofolate coenzymes are involved in the biochemical transfer of a one-carbon fragment at different oxidation levels. When the one-carbon unit is at the formic and oxidation level, the imidazoline with a five-membered ring structure is the active site. If benzimidazolium salt is used as tetrahydrofolate coenzyme model to react with nucleophilic reagent, such as Grignard reagent, the one-carbon unit at the formic acid oxidation level will be transferred to the nucleophilic reagent, and the biomimetic synthesis to initiate the one-carbon unit transfer reaction of tetrahydrofolate coenzyme will be accomplished.Long-chain diketones are an important class of compounds in view of the distinct structure feature and wide utility in medical industry, dyeing industry and organic synthesis. In this work, a convenient synthetic method for the preparation of long-chain diketones from long-chain dicarboxylic acids is provided. Eight bis-benzimidazolium salts were respectively used as tetrahydrofolate coenzyme model at formic acid oxidation level. Thus the biomimetic synthesis of three types of twenty-four long-chain diketones was successfully accomplished by using the addition-hydrolysis reaction of corresponding bis-benzimidazolium salts with methyl-magnesium-iodide, ethyl-magnesium-bromide or propyl-magnesium-bromide as nucleophile.Musk is a precious natural perfume and rare medicinal material. Muscone (3-methylcyclopentadecanone) is the main odorous principle of musk. We first reported the reaction of benzimidazolium salts with Grignard reagents. In this paper, we provided two biomimetic synthetic methods for muscone by using the addition-hydrolysis reaction of benzimidazolium salt as a new tetrahydrofolate coenzyme model with Grignard reagent. The two novel synthetic methods for muscone are as follows:First, muscone was prepared by hydrogenation of 3-methyl-2-cyclopenta-decene-1-one obtained from 2, 15-hexadecanedione. 2, 15-Hexadecanedione as animportant precursor of muscone was prepared by the addition-hydrolysis reaction of methyl-magnesium-iodide with bis-benzimidazolium salt. The said bis-benzimida-zolium salt can be synthesized from iodomethane and bis-benzimidazole obtained from 1, 2-benzenediamine and 1, 14-dodecanedicarboxylic. These starting materials are readily available. In this work, the bis-benzimidazolium salt was used as the methyl-substituted one-carbon unit model of tetrahydrofolate coenzyme, and thus the biomimetic synthesis of 2, 15-hexadecanedione, a precursor of muscone, was successfully accomplished by using the addition-hydrolysis reaction of bis-benzimidazolium salt with methyl-magnesium-iodide.Second, we provided a convenient synthetic method for muscone by the intramolecular addition-hydrolysis reaction of Grignard reagent with quaternary C=N bond of benzimidazolium salt, which served as the methyl-substituted one-carbon unit model of tetrahydrofolate coenzyme. The said benzimidazolium salt can be synthesized by using 1, 2-benzenediamine and 3-methyl-15-hydroxypentadecanoate as the starting materials. These starting materials are readily available. Thus a useful biomimetic synthetic method for muscone is provided.