37905-03-6Relevant articles and documents
Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX
Bogazkaya, Anna M.,Von Buehler, Clemens J.,Kriening, Sebastian,Busch, Alexandrine,Seifert, Alexander,Pleiss, Juergen,Laschat, Sabine,Urlacher, Vlada B.
supporting information, p. 1347 - 1353 (2014/07/22)
Allylic alcohols are valuable precursors in the synthesis of pharmaceutical intermediates, agrochemicals and natural products. Regioselective oxidation of parental alkenes is a challenging task for chemical catalysts and requires several steps including protection and deprotection. Many cytochrome P450 enzymes are known to catalyse selective allylic hydroxylation under mild conditions. Here, we describe CYP154E1 from Thermobifida fusca YX that enables this type of oxidation. Several acyclic terpenoids were tested as possible substrates for CYP154E1, and the regio- and chemoselectivity of their oxidation was investigated. Using a previously established bioinformatics approach we identified position 286 in the active site of CYP154E1 which is putatively involved in substrate binding and thereby might have an effect on enzyme selectivity. To tune regio- and chemoselectivity of the enzyme three mutants at position 286 were constructed and used for substrate oxidation. All formed products were analysed with GC-MS and identified using chemically synthesised authentic samples and known compounds as references. Best regioselectivity towards geraniol and nerol was observed with the wild type enzyme mainly leading to 8-hydroxy derivatives (8-hydroxygeraniol or 8-hydroxynerol) with high selectivity (100% and 96% respectively). Highest selectivities during the oxidation of geranylacetone and nerylacetone were observed with the following variants: V286F led mainly to 7-hydroxygeranylacetone (60% of the total product) and V286A produced predominantly 12-hydroxynerylacetone (75% of total product). Thus, CYP154E1 and its mutants expand the tool-box for allylic hydroxylation in synthetic chemistry.
Design and synthesis of biologically active analogues of vitamin K2: Evaluation of their biological activities with cultured human cell lines
Suhara, Yoshitomo,Hirota, Yoshihisa,Nakagawa, Kimie,Kamao, Maya,Tsugawa, Naoko,Okano, Toshio
, p. 3108 - 3117 (2008/09/19)
Novel ω-oxygenated vitamin K2 analogues were efficiently synthesized and their biological activities were evaluated. Some were biologically active and the side-chain played an important role in γ-carboxylation and apoptosis-inducing activity. The results provide useful information on the structure-activity relationship of vitamin K2 analogues for the development of new drugs.
PROCESS FOR PRODUCING OXYGENIC COMPOUND
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, (2008/06/13)
An oxidation catalyst composition is obtained by mixing a selenium compound, a nitrogen-containing aromatic compound and an acid, and if necessary, in the presence of a solvent. The oxidation catalyst composition shows an oxidation catalyst activity in the oxidation reaction of an organic compound. For example, at least one oxygen-containing compound selected from an alcohol compound, an aldehyde compound, a ketone compound and a carboxylic acid compound is obtained by reacting the olefin compound having two or more hydrogen atoms on the carbon atom at α-position of a carbon-carbon double bond with an organic hydroperoxide compound in the presence of the oxidation catalyst composition.