10148-70-6Relevant articles and documents
Multi-enzymatic synthesis of optically pure β-hydroxy α-amino acids
Hibi, Makoto,Kasahara, Takuya,Kawashima, Takashi,Yajima, Hiroko,Kozono, Shoko,Smirnov, Sergey V.,Kodera, Tomohiro,Sugiyama, Masakazu,Shimizu, Sakayu,Yokozeki, Kenzo,Ogawa, Jun
, p. 767 - 774 (2015)
A novel enzymatic production system of optically pure β-hydroxy α-amino acids was developed. Two enzymes were used for the system: an N-succinyl L-amino acid β-hydroxylase (SadA) belonging to the iron(II)/α-ketoglutarate-dependent dioxygenase superfamily and an N-succinyl L-amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N-succinyl aliphatic L-amino acids and produced N-succinyl β-hydroxy L-amino acids, such as N-succinyl-L-β-hydroxyvaline, N-succinyl-L-threonine, (2S,3R)-N-succinyl-L-β-hydroxyisoleucine, and N-succinyl-L-threo-β-hydroxyleucine. LasA catalyzed the desuccinylation of various N-succinyl-L-amino acids. Surprisingly, LasA is the first amide bond-forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L-leucine. By combining SadA and LasA in a preparative scale production using N-succinyl-L-leucine as substrate, 2.3 mmol of L-threo-β-hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β-hydroxy α-amino acids.
Total structure and inhibition of tumor cell proliferation of laxaphycins
Bonnard, Isabelle,Rolland, Marc,Salmon, Jean-Marie,Debiton, Eric,Barthomeuf, Chantal,Banaigs, Bernard
, p. 1266 - 1279 (2007)
From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides, The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.
A convenient synthesis of enantiomerically pure (2S,3S)- or (2R,3R)-3-hydroxyleucine
Caldwell,Bondy
, p. 34 - 36 (1990)
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Efficient chemoenzymatic synthesis of (2S,3S)-3-hydroxyleucine mediated by immobilised penicillin G acylase
Fadnavis, Nitin W.,Sharfuddin,Vadivel, S. Kumara,Bhalerao, Uday T.
, p. 3577 - 3578 (1997)
Immobilised penicillin G acylase (EC 3.5.1.11) has been used in the key step to obtain optically pure (2S,3S)-(+)-hydroxyleucine (ee >99%).
Asymmetric Aldol Reactions of Chiral Ni(II)-Complex of Glycine with Aliphatic Aldehydes. Stereodivergent Synthesis of syn-(2S)- and syn-(2R)-β-Alkylserines
Soloshonok, Vadim A.,Avilov, Dimitry V.,Kukhar, Valery P.,Tararov, Vitali I.,Savel'eva, Tatiana D.,et al.
, p. 1741 - 1756 (1995)
Stereoselectivity of aldol reactions between aliphatic aldehydes and Ni(II)-complex of chiral non-racemic Schiff base of glycine with (S)-o-benzophenone (BPB) in the presence of excess of MeONa, has been studied as a function of time, reaction conditions and nature of an aldehyde.Two salient features of the reaction, very high pseudokinetic syn-(2S)-diastereoselectivity, and dependence of thermodynamic syn-(2R)-diastereoselectivity on the steric bulk of an aldehyde side chain, were disclosed and used for efficient (more than 90percent de and ee) asymmetric synthesis of both syn-(2S) and syn-(2R)-3-alkyl substituted serines.Synthetic potential and reliability of this asymmetric method are demonstrated with the large scale (2-20 g) preparation of enantiomerically pure amino acids.
An enantioselective synthesis of (2S,3S)- and (2R,3S)-3-hydroxyleucine
Correy,Lee, Duck-Hyung,Choi, Soongyu
, p. 6735 - 6738 (1992)
α-Bromo β-hydroxy ester 2 was prepared in a preparative scale by a 96 : 4 enantioselective aldol reaction of t-butyl bromoacetate with isobutyraldehyde and converted efficiently to either (2S,3S)-or (2R,3S)-3-hydroxyleucine (7 or 11).
L -Threonine Transaldolase Activity Is Enabled by a Persistent Catalytic Intermediate
Kumar, Prasanth,Meza, Anthony,Ellis, Jonathan M.,Carlson, Grace A.,Bingman, Craig A.,Buller, Andrew R.
, p. 86 - 95 (2021/01/09)
l-Threonine transaldolases (lTTAs) are a poorly characterized class of pyridoxal-5′-phosphate (PLP) dependent enzymes responsible for the biosynthesis of diverse β-hydroxy amino acids. Here, we study the catalytic mechanism of ObiH, an lTTA essential for biosynthesis of the β-lactone natural product obafluorin. Heterologously expressed ObiH purifies as a mixture of chemical states including a catalytically inactive form of the PLP cofactor. Photoexcitation of ObiH promotes the conversion of the inactive state of the enzyme to the active form. UV-vis spectroscopic analysis reveals that ObiH catalyzes the retro-aldol cleavage of l-threonine to form a remarkably persistent glycyl quinonoid intermediate, with a half-life of a??3 h. Protonation of this intermediate is kinetically disfavored, enabling on-cycle reactivity with aldehydes to form β-hydroxy amino acids. We demonstrate the synthetic potential of ObiH via the single step synthesis of (2S,3R)-β-hydroxyleucine. To further understand the structural features underpinning this desirable reactivity, we determined the crystal structure of ObiH bound to PLP as the Schiff's base at 1.66 ? resolution. This high-resolution model revealed a unique active site configuration wherein the evolutionarily conserved Asp that traditionally H-bonds to the cofactor is swapped for a neighboring Glu. Molecular dynamics simulations combined with mutagenesis studies indicate that a structural rearrangement is associated with l-threonine entry into the catalytic cycle. Together, these data explain the basis for the unique reactivity of lTTA enzymes and provide a foundation for future engineering and mechanistic analysis.
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.
