20312-37-2Relevant academic research and scientific papers
Synthesis of 2-hydroxy acid from 2-amino acid by Clostridium butyricum
Khelifa, Nasser,Butel, Marie-Jose,Rimbault, Alain
, p. 3429 - 3434 (1998)
Cultures of Clostridium butyricum type strain in synthetic medium supplemented with various L-2-amino acids revealed the presence of the corresponding 2-hydroxy acid. This metabolite is able to produce the polyester poly(2-hydroxyalkanoic acid). The bioconversion is not stereoselective since D-2-amino acids were also converted. Chiral GC analysis demonstrated that only D-enantiomer is formed from L-leucine.
Structure revision of isocereulide A, an isoform of the food poisoning emetic Bacillus cereus toxin cereulide
Ehling-Schulz, Monika,Hofmann, Thomas F.,Kranzler, Markus,Stark, Timo D.,Walser, Veronika
supporting information, (2021/05/31)
The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A-G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an L-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESITOF- MS, as well as MSn sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the L-O-Leu as assumed to date, one L-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(D-O-Leu-D-Ala-L-O-Val-L-Val)2(DO- Leu-D-Ala-L-O-Ile-L-Val)].
Efficient Synthesis of D-Phenylalanine from L-Phenylalanine via a Tri-Enzymatic Cascade Pathway
Lu, Cui,Zhang, Sheng,Song, Wei,Liu, Jia,Chen, Xiulai,Liu, Liming,Wu, Jing
, p. 3165 - 3173 (2021/06/09)
D-phenylalanine is an important intermediate in food and pharmaceutical industries. Here, to enable efficient D-phenylalanine biosynthesis from L-phenylalanine, a tri-enzymatic cascade was designed and reconstructed in vivo. The activity of Proteus vulgaris meso-diaminopimelate dehydrogenase (PvDAPDH) toward phenyl pyruvic acid was identified as the limiting step. To overcome, the tension in the phenyl pyruvic acid side-chain, PvDAPDH was engineered, generating PvDAPDHW121A/R181S/H227I, whose catalytic activity of 6.86 U mg?1 represented an 85-fold increase over PvDAPDH. Introduction of PvDAPDHW121A/R181S/H227I, P. mirabilis L-amino acid deaminase, and Bacillus megaterium glucose dehydrogenase in E. coli enabled the production of 57.8 g L?1 D-phenylalanine in 30 h, the highest titer to date using 60 g L?1 L-phenylalanine as starting substrate, which meant a 96.3 % conversion rate and >99 % enantioselectivity on a 3-L scale. The proposed tri-enzymatic cascade provides a novel potential bio-based approach for industrial production of D-phenylalanine from cheap amino acids.
Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis
Zhang, Shuwei,Qiu, Yixing,Kakule, Thomas B.,Lu, Zhenyu,Xu, Fuchao,Lamb, John G.,Reilly, Christopher A.,Zheng, Yong,Sham, Shing Wo Simon,Wang, Wei,Xuan, Lijiang,Schmidt, Eric W.,Zhan, Jixun
, p. 363 - 370 (2017/03/08)
Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the calcium channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel. Through genome sequencing and targeted gene disruption, a noniterative nonribosomal peptide synthetase was found to be involved in the biosynthesis of leualacin. A comparison of the structures of leualacin and its analogues indicated that the A2 and A4 domains of the leualacin synthetase are substrate specific, while A1, A3, and A5 can accept alternative precursors to yield new molecules.
Medusamide a, a panamanian cyanobacterial depsipeptide with multiple β-amino acids
Fenner, Amanda M.,Engene, Niclas,Spadafora, Carmenza,Gerwick, William H.,Balunas, Marcy J.
, p. 352 - 355 (2016/02/19)
From a collection of marine cyanobacteria made in the Coiba National Park along the Pacific coast of the Republic of Panama a novel cyclic depsipeptide, given the trivial name medusamide A, has been isolated and fully characterized. Medusamide A contains four contiguous β-amino acid (2R,3R)-3-amino-2-methylhexanoic acid (Amha) residues. This is the first report of multiple Amha residues and contiguous β-amino acid residues within a single cyclic peptide-type natural product. Stereochemical assignment of the Amha residues was completed following the synthesis of reference standards for this β-amino acid and the subsequent derivatization with Marfey's reagent and LC-MS analysis.
Asymmetric Assembly of All-Carbon Tertiary/Quaternary Nonadjacent Stereocenters through Organocatalytic Conjugate Addition of α-Cyanoacetates to a Methacrylate Equivalent
Iriarte, Igor,Vera, Silvia,Badiola, Eider,Mielgo, Antonia,Oiarbide, Mikel,García, Jesús M.,Odriozola, José M.,Palomo, Claudio
supporting information, p. 13690 - 13696 (2016/09/13)
An efficient, highly diastereo- and enantioselective assembly of acyclic carbonyl fragments possessing nonadjacent all-carbon tertiary/quaternary stereoarrays is reported based on a Br?nsted base catalyzed Michael addition/α-protonation sequence involving α-cyanoacetates and 2,4-dimethyl-4-hydroxypenten-3-one as novel methacrylate equivalent.
Biocontrolled formal inversion or retention of L -α-amino acids to enantiopure (R)- or (S)-hydroxyacids
Busto, Eduardo,Grischek, Barbara,Kroutil, Wolfgang,Richter, Nina
, p. 11225 - 11228,4 (2015/01/07)
Natural L-α-amino acids and L-norleucine were transformed to the corresponding α-hydroxy acids by formal biocatalytic inversion or retention of absolute configuration. The one-pot transformation was achieved by a concurrent oxidation reduction cascade in aqueous media. A representative panel of enantiopure (R)- and (S)-2-hydroxy acids possessing aliphatic, aromatic and heteroaromatic moieties were isolated in high yield (67-85 %) and enantiopure form (>99 % ee) without requiring chromatographic purification.
Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides
Kang, Chang Won,Ranatunga, Sujeewa,Sarnowski, Matthew P.,Del Valle, Juan R.
supporting information, p. 5434 - 5437 (2015/02/19)
The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).
Photoreaction of rac-Leucine in ice by circularly polarized synchrotron radiation: Temperature-induced mechanism switching from Norrish type II to deamination
Nishino, Hideo,Hosaka, Masahito,Katoh, Masahiro,Inoue, Yoshihisa
, p. 13929 - 13936 (2013/10/22)
The delivery of extraterrestrial organics to primitive Earth is considered to have triggered the origin and subsequent evolution of life. Indeed, enantiomerically enriched amino acids of nonterrestrial origin have been found in carbonaceous meteorites, and enantioselective photodecomposition by circularly polarized light (CPL) in outer space has been proposed to have played some role in the initial enantiomeric bias. To experimentally examine this possibility and elucidate the photoreaction mechanisms, we have studied the photolysis of racemic leucine (rac-Leu) in acidic and neutral ice/water media at 21-298 K with left- and right-CPL in an attempt to detect enantiomerically enriched D- and L-Leu, respectively. Comprehensive product analyses revealed that the CPL-induced deracemization of Leu proceeds in both acidic and neutral ice matrices even at 21 K, and that the main mechanism switches from Norrish-type II γ-hydrogen abstraction to SNi deamination on lowering the temperature. The potential role of the CPL-induced photodecomposition of amino acids as a source of the enantiomer imbalance in meteorites is discussed. ET arrives! Enantioselective photoreaction of rac-leucine by circularly polarized synchrotron radiation proceeds in both neutral and acidic ices at temperatures down to 21 K, with the main mechanism switching from Norrish type II γ-hydrogen abstraction to SNi deamination by lowering the irradiation temperature (see figure). Copyright
Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
Jia, Chao,Yang, Ke-Wu,Liu, Cheng-Cheng,Feng, Lei,Xiao, Jian-Min,Zhou, Li-Sheng,Zhang, Yi-Lin
supporting information; experimental part, p. 482 - 484 (2012/03/11)
VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on β-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX.
