104069-26-3Relevant articles and documents
Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases
Klein, Christian,Huettel, Wolfgang
, p. 1643 - 1647 (2011)
The enzymatic synthesis of tertiary alcohols by the stereospecific oxidation of tertiary alkyl centers is a most-straightforward but challenging approach, since these positions are sterically hindered. In contrast to P450-monooxygenases, there is little known about the potential of non-heme iron(II) oxygenases to catalyze such reactions. We have studied the hydroxylation of trans-3-methyl-Lproline with the a-ketoglutarate (α-KG) dependent oxygenases, cis-3-proline hydroxylase type II and cis-4-proline hydroxylase (cis-P3H-II and cis-P4H). With cis-P3H-II, the tertiary alcohol product (3R)-3-hydroxy-3-methyl-L-proline was obtained exclusively but in reduced yield (～7%) compared to the native substrate L-proline. For cis-P4H, a complete shift in regioselectivity from C-4 to C-3 was observed so that the same product as with cis-P3H-II was obtained. Moreover, the yields were at least as good as in control reactions with L-proline (～110% relative yield). This result demonstrates a remarkable potential of non-heme iron(II) oxygenases to oxidize substrates selectively at sterically hindered positions. 10.3762/bjoc.7.193.
Cyclothialidine analogs, novel DNA gyrase inhibitors
Yamaji, Kayoko,Masubuchi, Miyako,Kawahara, Fumiko,Nakamura, Yumiko,Nishio, Aya,Matsukuma, Shoko,Fujimori, Mikako,Nakada, Naoki,Watanabe, Junko,Kamiyama, Tsutomu
, p. 402 - 411 (1997)
DNA gyrase inhibitors, cyclothialidines B, C, D and E were isolated from four Streptomycete strains (NR 0659, NR 0660, NR 0661 and NR 0662). Their structures have been elucidated based on the amino acid analysis of the hydrolysates, NMR and HRFAB-MS experiments and shown to be cyclothialidine analogs. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates. Cyclothialidines B, D and E are novel and potent inhibitors of DNA gyrase.
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Irreverre et al.
, p. 2824,2830 (1963)
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Differential oxidation of endocyclic enecarbamates. Synthesis of cyclic β-hydroxy-α-amino acids
Sugisaki, Claudia H.,Carroll, Patrick J.,Correia, Carlos Roque D.
, p. 3413 - 3416 (1998)
The differential oxidation of five and six-membered endocyclic enecarbamates was investigated employing m-CPBA, DMD, as well as enantioselectivc protocols such as the Kochi-Jacobsen-Katsuki's epoxidation and the Sharpless dihydroxylation. By this strategy the syntheses of β- hydroxyprolines and β-hydroxypipecolic acids were accomplished, X-Ray crystallographic analysis of the trans-β-hydroxypipecolic acid was instrumental to solve structural assignment conflicts.
Discovery of New Fe(II)/α-Ketoglutarate-Dependent Dioxygenases for Oxidation of l-Proline
Dussauge, Solene,Moore, Charles,Snajdrova, Radka,Tassano, Erika,Vargas, Alexandra
supporting information, (2022/02/09)
Genome mining for novel Fe(II)/α-ketoglutarate-dependent dioxygenases (αKGDs) to expand the enzymatic repertoire in the oxidation of l-proline is reported. Through clustering of proteins, we predicted regio- and stereoselectivity in the hydroxylation reaction and validated this hypothesis experimentally. Two novel byproducts in the reactions with enzymes from Bacillus cereus and Streptomyces sp. were isolated, and the structures were determined to be a 3,4-epoxide and a 3,4-diol, respectively. The mechanism for the formation of the epoxide was investigated by performing an 18O-labeling experiment. We propose that the mechanism proceeds via initial cis-3-hydroxylation followed by ring closure. A biocatalytic step was run on subgram quantities of starting material without any significant optimization of the conditions. However, the substrate concentration was 40-fold higher than the usual reported titers for recombinant P450-mediated hydroxylations, showing the synthetic potential of αKGDs on a preparative scale.
Studies on the selectivity of proline hydroxylases reveal new substrates including bicycles
Smart, Tristan J.,Hamed, Refaat B.,Claridge, Timothy D.W.,Schofield, Christopher J.
supporting information, (2019/11/26)
Studies on the substrate selectivity of recombinant ferrous-iron- and 2-oxoglutarate-dependent proline hydroxylases (PHs) reveal that they can catalyse the production of dihydroxylated 5-, 6-, and 7-membered ring products, and can accept bicyclic substrates. Ring-substituted substrate analogues (such hydroxylated and fluorinated prolines) are accepted in some cases. The results highlight the considerable, as yet largely untapped, potential for amino acid hydroxylases and other 2OG oxygenases in biocatalysis.
Regio- and stereoselective oxygenation of proline derivatives by using microbial 2-oxoglutarate-dependent dioxygenases
Hara, Ryotaro,Uchiumi, Naoko,Okamoto, Naoko,Kino, Kuniki
, p. 1384 - 1388 (2015/07/20)
We evaluated the substrate specificities of four proline cis-selective hydroxylases toward the efficient synthesis of proline derivatives. In an initial evaluation, 15 proline-related compounds were investigated as substrates. In addition to L-proline and L-pipecolinic acid, we found that 3,4-dehydro-L-proline, L-azetidine-2-carboxylic acid, cis-3-hydroxy-L-proline, and L-thioproline were also oxygenated. Subsequently, the product structures were determined, revealing cis-3,4-epoxy-L-proline, cis-3-hydroxy-L-azetidine-2-carboxylic acid, and 2,3-cis-3,4-cis-3,4-dihydroxy-L-proline.
