153829-66-4Relevant academic research and scientific papers
Total Synthesis of Skyllamycins A–C
Giltrap, Andrew M.,Haeckl, F. P. Jake,Kurita, Kenji L.,Linington, Roger G.,Payne, Richard J.
, p. 15046 - 15049 (2017/10/31)
The skyllamycins are a family of highly functionalized non-ribosomal cyclic depsipeptide natural products which contain the extremely rare α-OH-glycine functionality. Herein the first total synthesis of skyllamycins A–C is reported, together with the biofilm inhibitory activity of the natural products. Linear peptide precursors for each natural product were prepared through an efficient solid-phase route incorporating a number of synthetic modified amino acids. A novel macrocyclization step between a C-terminal amide and an N-terminal glyoxylamide moiety served as a key transformation to install the unique α-OH-glycine unit and generate the natural products in the final step of the synthesis.
Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids
Davies, Stephen G.,Fletcher, Ai M.,Frost, Aileen B.,Roberts, Paul M.,Thomson, James E.
, p. 5849 - 5862 (2015/03/30)
The β-hydroxy-α-amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-amino esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-amino esters were prepared in >99:1 dr using our diastereoselective aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (-)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-amino esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-amino esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-amino acids in good yield and high diastereoisomeric and enantiomeric purity.
Biocatalytic Synthesis of Enantiopure β-Methoxy-β-arylalanine Derivatives
Fan, Shiming,Liu, Shouxin,Zhang, Hubo,Liu, Ying,Yang, Yihuang,Jin, Longyi
, p. 5591 - 5597 (2014/10/15)
Chiral β-hydroxy-β-arylalanine and β-methoxy-β-arylalanine derivatives, which occur widely in marine nature products, were stereoselectively synthesized with 99 % ee values. The two erythro isomers were prepared by L- or D-aminoacylase-catalyzed resolution of the corresponding N-acetyl derivatives, whereas the two threo isomers were obtained only by D-aminoacylase-catalyzed resolution of the derivatives. erythro-β-Hydroxy-β-arylalanine derivatives were prepared by diastereoselective hydrogenation of ethyl 2-(hydroxyimino)-3-oxo-3-arylpropanoates, which were in turn acquired by the oximation of ethyl 3-oxo-3-arylpropanoates with ethyl nitrite in the presence of nano-K2CO3 with yields of 72 % to 80 %. β-Methoxy-β-arylalanine derivatives were synthesized through Williamson reactions between the corresponding β-hydroxy-β-arylalanines and iodomethane with silver oxide as base.
Stereoselective Synthesis of Threo and Erythro β-Hydroxy and β-Disubstituted-β-Hydroxy α-Amino Acids
Blaskovich, Mark A.,Evindar, Ghotas,Rose, Nicholas G. W.,Wilkinson, Scott,Luo, Yue,Lajoie, Gilles A.
, p. 3631 - 3646 (2007/10/03)
Optically pure N-protected serine aldehyde equivalents can be prepared by the protection of the carboxylic group of serine by a cyclic ortho ester. Alkylation of N-Cbz-, N-Fmoc- or N-Boc-protected serine with oxetane tosylate 1 or bromide 2 gives the corresponding oxetane esters 4a-c which can easily be converted to the cyclic ortho esters 5a-c. A variety of unusual threo β5-hydroxy amino acids have been synthesized by Grignard addition to these optically pure serine aldehyde equivalents. The erythro diastereomers can be obtained by oxidation of the initial threo adduct followed by reduction with LiBH4. Also described is a general approach for the diastereoselective synthesis of optically pure β,β-dialkyl-β-hydroxy α-amino acids. These highly substituted amino acids are prepared by a sequence of Grignard addition to the optically active serine aldehyde equivalent, followed by oxidation of the initial adduct, and a second Grignard addition to the resulting ketone. The hydroxy adduct is obtained with very high diastereoselectivity (84-96% de). All four diastereomers can be selectively synthesized by varying the order of the Grignard additions and the chirality of the initial synthon. Removal of the protecting groups can be effected in very mild conditions, giving excellent yields of highly substituted amino acids in high diastereomeric purity.
A new enantioselective synthesis of (2R,3S)-3-(4-methoxyphenyl)glycidic ester via the enzymatic hydrolysis of erythro-N-acetyl-β-(4- methoxyphenyl)serine
Inoue,Matsuki,Oh-Ishi
, p. 1521 - 1523 (2007/10/02)
Enantioselective synthesis of (2R,3S)-3-(4-methoxyphenyl)glycidic ester ((2R,3S)-1) via the enzymatic hydrolysis of erythro-N-acetyl-β-(4- methoxyphenyl)serine (9) was investigated. Treatment of the obtained α- amino acid (-)-10 with NaNO2-KBr-dilute H2SO4, esterification, and subsequent oxiran-ring closure of the halohydrin gave the target compound (2R,3S)-1 with high enantiomeric excess (94% ee).
