76454-94-9Relevant academic research and scientific papers
Efficient incorporation of unsaturated methionine analogues into proteins in vivo
Van Hest, Jan C. M.,Kiick, Kristi L.,Tirrell, David A.
, p. 1282 - 1288 (2007/10/03)
A set of eight methionine analogues was assayed for translational activity in Escherichia coli. Norvaline and norleucine, which are commercially available, were assayed along with 2-amino-5-hexenoic acid (2), 2-amino-5-hexynoic acid (3), cis-2-amino-4-hexenoic acid (4), trans-2-amino-4-hexenoic acid (5), 6,6,6-trifluoro-2-aminohexanoic acid (6), and 2-aminoheptanoic acid (7), each of which was prepared by alkylation of diethyl acetamidomalonate with the appropriate tosylate, followed by hydrolysis. The E. coli methionine auxotroph CAG18491, transformed with plasmids pREP4 and pQE15, was used as the expression host, and translational activity was assayed by determination of the capacity of the analogue to support synthesis of the test protein dihydrofolate reductase (DHFR) in the absence of added methionine. The importance of amino acid side chain length was illustrated by the fact that neither norvaline (8) nor 7 showed translational activity, in contrast to norleucine (9), which does support protein synthesis under the assay conditions. The internal alkene functions of 4 and 5 prevented incorporation of these analogues into test protein, and the fluorinated analogue 6 yielded no evidence of translational activity. The terminally unsaturated compounds 2 and 3, however, proved to be excellent methionine surrogates: 1H NMR spectroscopy, amino acid analysis, and N-terminal sequencing indicated ～85% substitution of methionine by 2, while 3 showed 90-100% replacement. Both analogues also function efficiently in the initiation step of protein synthesis, as shown by their near-quantitative occupancy of the N-terminal amino acid site in DHFR. Enzyme kinetics assays were conducted to determine the rate of activation of each of the methionine analogues by methionyl tRNA synthetase (MetRS); results of the in vitro assays corroborate the in vivo incorporation results, suggesting that success or failure of analogue incorporation in vivo is controlled by MetRS.
Enantioselective Preparation of 3-Substituted-4-pentenoic Acids via the Claisen Rearrangement
Kurth, Mark J.,Decker, Owen H. W.
, p. 5769 - 5775 (2007/10/02)
Asymmetric C-C bond formation via the diastereoselective aza-Claisen rearrangement of N-allylketene N,O-acetal 4 is described.The starting materials, allylic alkylating agant 1 and optically pure oxazoline 2, are easily prepared and, in a one-pot procedure, generate rearranged oxazolines 5 in 52-94percent diastereomeric excess.The overall chemical yields for 2 -> 5 range from 51 to 78percent.The aza-Claisen rearrangement (4 -> 5) proceeds with excellent N,O-acetal face selectivity and with good to excellent chair selectivity.Hydrolysis of rearranged oxazoline 5 completes an enantioselective synthesis of 3-substituted pent-4-enoic acids.
Diastereoselective α Allylation of Secondary and Tertiary Thioamides via Thio-Claisen Rearrangement. A Structural Proof of Z Secondary Thioamide Dianions and Z Tertiary Thioamide Anions
Tamaru, Y.,Furukawa, Y.,Mizutani, M.,Kitao, O.,Yoshida, Z.
, p. 3631 - 3639 (2007/10/02)
Highly diastereoselective α allylation of secondary and tertiary thioamides is achieved by making use of thio-Claisen rearrangement.From the correlation between the diastereoselectivities in products and the structures of allylating agents, the Z structures of secondary thioamide dianion (ca. 100percent Z) and tertiary thioamide anion (>97percent Z) are concluded.
