2280-27-5

Usage

Chemical Properties

white powder

InChI:InChI=1/C5H11NO3/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1

Upstream product

• 20902-45-8 D-Penicillamin-disulfid 
• 120-57-0 piperonal 
• 96293-17-3 (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide 
• 56-40-6 glycine 
• 67-64-1 acetone 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 102507-13-1 N-(tert-butoxycarbonyl)-3-hydroxy-L-valine 
• 473545-40-3 tert-butyl N-[(1R)-2-hydroxy-1-(hydroxymethyl)-2-methylpropyl]carbamate 
• 288159-36-4 tert-butyl (4R)-4-(1-hydroxy-1-methylethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 
• 52-67-5 3,3-dimethyl-D-cysteine 

Downstream Products

• 73739-09-0 (S)-3-benzoyl-5,5-dimethyl-oxazolidine-4-carboxylic acid 
• 72-18-4 L-valine 
• 56-40-6 glycine 
• 112110-89-1 N-[(Phenylmethoxy)carbonyl]-L-β-hydroxyvaline 
• 102507-13-1 N-(tert-butoxycarbonyl)-3-hydroxy-L-valine 
• 1217603-41-2 (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-hydroxy-3-methylbutanoic acid 
• 1571213-08-5 (S)-4-benzyl-2,2-dimethyl-5-oxomorpholine-3-carboxylic acid 
• 40869-41-8 (S)-2-(benzylamino)-3-hydroxy-3-methylbutanoic acid 
• 1363374-34-8 C₂₃H₂₂N₂O₄ 

Relevant academic research and scientific papers

Gold-Catalyzed Amide/Carbamate-Linked N, O-Acetal Formation with Bulky Amides and Alcohols

A gold-catalyzed N,O-acetal formation was established to construct an amide/carbamate-linked N,O-acetal substructure with bulky alcohols. The acyliminium cation species generated from o-alkynylbenzoic acid ester in the presence of a gold catalyst is highly reactive and underwent nucleophilic attack of various bulky alcohols and phenols at room temperature under neutral conditions, leading to the corresponding N,O-acetals in yields of 34-89% with good functional group tolerance.

Multi-enzymatic synthesis of optically pure β-hydroxy α-amino acids

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 synthesis of the large non-ribosomal peptide polytheonamide B

Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 =68 pg ml -1 , mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30A? in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity.

A new synthesis of enantiomerically pure syn-(S)-β-hydroxy-α-amino acids via asymmetric aldol reactions of aldehydes with a homochiral Ni(II)-glycine/(S)-BPB Schiff base complex

syn-(S)-β-Hydroxy-α-amino acids were synthesised stereoselectively via elaboration of the asymmetric aldol reactions of aldehydes with a chiral Ni(II)-(S)-BPB/glycine Schiff base complex in the presence of equimolar NaH in THF. The stereoselectivity of the reaction was studied as a function of time, the reaction conditions, the nature of the carbonyl compounds and the base used. The synthetic potential of this asymmetric method was demonstrated in the preparation of syn-(S)-β-hydroxyleucine on a multi-gram scale.

3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation

γ-Irradiation of several amino acids (Val, Leu, Ile, Lys, Pro, and Glu) in the presence of O2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO°attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3- hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4- hydroxyhexanoic acid], (2S,5R)5-hydroxylysine [(2S,5R)-2,6-diamino-5- hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5- hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9- fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu- Phe) and proteins (BSA and histone H1) exposed to HO°/O2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.

Stereoselective Synthesis of Threo and Erythro β-Hydroxy and β-Disubstituted-β-Hydroxy α-Amino Acids

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.

New anticancer antibiotics pelagiomicins. Produced by a new marine bacterium Pelagiobacter variabilis

In the course of our screening for new anticancer compounds produced by marine bacteria, we found that a new genus marine bacterium Pelagiobacter variabilis produced new phenazine antibiotics, pelagiomicins A, B and C. Those compounds were labile in water and alcohols. The absolute structure of the main component, pelagiomicin A, and the structures of the minor ones were determined from the spectroscopic data and by synthesis. Pelagiomicin A exhibits activity against Gram-positive and-negative bacteria and antitumor activity in vitro and in vivo.

General Method of Diastereo- and Enantioselective Synthesis of β-Hydroxy-α-amino Acids by Condensation of Aldehydes and Ketones with Glycine

The condensation of formaldehyde with a Ni(II) complex of glicyne Schiff base with (S)-2-acetophenone (1) or (S)-2-benzophenone (2) in CH3OH at 25 deg C in the presence of Et3N yields (S)-Ser with an enantiomeric excess (ee) of 80-90percent.The same reaction gives rise to (R)-Ser with an ee greater than 80percent in the presence of more than 0.2 N CH3ONa, α-(hydroxymethyl) serine being formed in negligible quantities.The reaction of benzaldehyde, 3,4-(methilenedioxy)benzaldehyde, and acetaldehyde with these Gly complexes in 0.2 N CH3ONa at 25 deg C yields β-hydroxy-α-amino acids: (R)-β-phenylserine, (R)-3,4-(methylenedioxy)-β-phenylserine, and (R)-threonine, respectively, with a threo/allo ratio ranging from 10:1 up to over 50:1 and ee more than 80percent.Condensation with acetone yields (R)-β-hydroxyvaline with an enantiomeric purity of 70percent.The enantiomerically pure β-hydroxy-α-amino acids can be obtained from pure diastereomers, isolated by chromatography on silica or Toyopearl HW-60.The initial reagents 1 and 2 were recovered with 60-98percent yield.The stereochemical mechanism of the reaction is discussed.

Process for the production of β-hydroxy-α-aminocarboxylic acids

β-hydroxy-α-aminocarboxylic acids of the formula: STR1 where R1 and R2 are hydrogen or an alkyl group having 1 to 10 carbon atoms are produced by hydrogenating the correspondingly substituted cyanohydrin in a water containing medium first in the presence of a hydrogenation catalyst and an acid at a temperature between -10° and +40° C. and a hydrogen pressure of less than 10 bar, until per mole of cyanohydrogen employed one mole of hydrogen is taken up and then employing the solution obtained as starting material for a Strecker or Bucherer synthesis of an amino acid.