55674-67-4

Basic information

• Product Name: BOC-D-THR-OH
• Synonyms: N-ALPHA-TERT-BUTOXYCARBONYL-D-THREONINE;N-ALPHA-T-BUTOXYCARBONYL-D-THREONINE;N-ALPHA-T-BOC-D-THREONINE;N-ALPHA-T-BOC-D-THREONINE / (2R,3S);N-TERT-BUTOXYCARBONYL-D-THREONINE;BOC-D-THR-OH;BOC-D-THREONINE;BOC-D-THR
• CAS NO: 55674-67-4
• Molecular Formula: C₉H₁₇NO₅
• Molecular Weight: 219.23
• Product Categories: Threonine [Thr, T];Boc-Amino Acids and Derivative;Amino Acids;Amino Acids (N-Protected);Biochemistry;Boc-Amino Acids
• Mol File: 55674-67-4.mol

Chemical Properties

• Melting Point: 81 °C
• Boiling Point: 387.1oC at 760 mmHg
• Flash Point: 187.9oC
• Appearance: /Solid
• Density: 1.202g/cm3
• Vapor Pressure: 1.36E-07mmHg at 25°C
• Refractive Index: 9 ° (C=1, AcOH)
• Storage Temp.: Store at RT.
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: BOC-D-THR-OH(CAS DataBase Reference)
• NIST Chemistry Reference: BOC-D-THR-OH(55674-67-4)
• EPA Substance Registry System: BOC-D-THR-OH(55674-67-4)

Safety Data

• Hazardous Substances Data: 55674-67-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
BOC-D-THR-OH is used as a synthetic intermediate for the production of chiral antibiotics. Its unique stereochemistry and functional groups make it a valuable component in the development of new and effective drugs.
Used in Microbiology Research:
BOC-D-THR-OH is used as an inhibitor of growth and cell wall synthesis of Mycobacterium smegmatis, a bacterium commonly used in microbiological research. This application helps scientists study the mechanisms of bacterial growth and develop new strategies for combating bacterial infections.

InChI:InChI=1/C9H17NO5/c1-5(11)6(7(12)13)10-8(14)15-9(2,3)4/h5-6,11H,1-4H3,(H,10,14)(H,12,13)/t5-,6-/m1/s1

Upstream product

• 24830-94-2 D-allo-threonine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 28954-12-3 (2S,3S)-2-amino-3-hydroxybutanoic acid 
• 34619-03-9 tert-butyldicarbonate 
• 72-19-5 DL-threonine 
• 72-19-5 rac-allo-threonine 
• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 632-20-2 D-Threonine 
• 924-49-2 DL-4-amino-3-hydroxybutyric acid 
• 909114-65-4 tert-butyl 4,6-dimethoxy-1,3,5-triazinyl carbonate 
• 1262723-05-6 tert-butyl (1S,2S)-1-((2-oxo-2-(pyren-3-yl)ethoxy)carbonyl)-2-hydroxypropylcarbamate 
• 113525-91-0 (2S,3S)-methyl 2-[(tert-butoxycarbonyl)amino]-3-hydroxybutanoate 

Downstream Products

• 936703-31-0 C₁₉H₂₈N₂O₆ 
• 174698-98-7 [(1S,2S)-2-Hydroxy-1-((R)-1-phenyl-ethylcarbamoyl)-propyl]-carbamic acid tert-butyl ester 
• 96099-84-2 (2R,3S)-methyl 2-<(tert-butoxycarbonyl)amino>-3-hydroxybutanoate 
• 69355-99-3 Boc-O-benzyl-D-threonine 
• 437631-41-9 BOC-L-α-Thr-L-Phe-OBn 
• 868553-65-5 [(1R,2S)-2-Hydroxy-1-(4-octyl-phenylcarbamoyl)-propyl]-carbamic acid tert-butyl ester 
• 1396972-31-8 (2R,3S)-2-(tert-butoxycarbonylamino)-3-methoxybutanoic acid 
• 1374666-80-4 (2S,3S)-allo-2-methyl-4-oxo-3-oxetanylcarbamic acid tert-butyl ester 
• 347191-37-1 Boc-L-aThr-L-Phe-L-Pro-Thz-OMe 
• 742060-65-7 Boc-L-allo-Thr-OBn 

Relevant articles and documents

Optimization of globomycin analogs as novel gram-negative antibiotics

Discovery of novel classes of Gram-negative antibiotics with activity against multi-drug resistant infections is a critical unmet need. As an essential member of the lipoprotein biosynthetic pathway, lipoprotein signal peptidase II (LspA) is an attractive target for antibacterial drug discovery, with the natural product inhibitor globomycin offering a modestly-active starting point. Informed by structure-based design, the globomycin depsipeptide was optimized to improve activity against E. coli. Backbone modifications, together with adjustment of physicochemical properties, afforded potent compounds with good in vivo pharmacokinetic profiles. Optimized compounds such as 51 (E. coli MIC 3.1 μM) and 61 (E. coli MIC 0.78 μM) demonstrate broad spectrum activity against gram-negative pathogens and may provide opportunities for future antibiotic discovery.

CYCLIC PEPTIDE ANTIBIOTICS

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of lipoprotein signal peptidase II (LspA), a key protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

KCNT1 INHIBITORS AND METHODS OF USE

The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

CYCLIC PEPTIDE ANTIBIOTICS

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of lipoprotein signal peptidase II (LspA), a key protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Synthesis of the Siderophore Coelichelin and Its Utility as a Probe in the Study of Bacterial Metal Sensing and Response

A convergent total synthesis of the siderophore coelichelin is described. The synthetic route also provided access to acetyl coelichelin and other congeners of the parent siderophore. The synthetic products were evaluated for their ability to bind ferric iron and promote growth of a siderophore-deficient strain of the Gram-negative bacterium Pseudomonas aeruginosa under iron restriction conditions. The results of these studies indicate coelichelin and several derivatives serve as ferric iron delivery vehicles for P. aeruginosa.

Synthesis of macrocyclic precursors of the vioprolides

The vioprolides are novel depsipeptides that have not been synthesized. However, they have been identified as important targets for synthesis because of their novel biological activities and challenging chemical structures. Following early work on the synthesis of a modified tetrapeptide that contained both the (E)-dehydrobutyrine and thiazoline components of vioprolide D, problems were encountered in taking an (E)-dehydrobutyrine containing intermediate further into the synthesis. A second approach to vioprolides and analogues was therefore investigated in which (E)- and (Z)-dehydrobutyrines were to be introduced by selenoxide elimination very late in the synthesis. A convergent approach to advanced macrocyclic precursors of the vioprolides was then completed using a modified hexapeptide and a dipeptidyl glycerate. In this work, it was necessary to protect the 2-hydroxyl group of the glycerate as its acetate and not as its 2,2,2-trichloroethoxycarbonate. Preliminary studies were carried out on the introduction of the required dehydrobutyrine and thiazoline components into advanced intermediates.

Heteroatom-Interchanged Isomers of Lissoclinamide 5: Copper(II) Complexation, Halide Binding, and Biological Activity

Cyclic peptides, especially those produced by marine cyanobacteria symbionts, are considered to play an important ecological role in host defence. Chemists have long compared the cyclic peptide cavitand architecture with that of macrocyclic ligands, and proposed that they mediate metal-ion transport. The study presented herein investigated the metal chelation of non-natural heteroatom-interchanged (HI) isomers of lissoclinamide 5, by using MS, EPR, and DFT calculations. The latter identified three possible structures for the CuII complex with natural lissoclinamide 5, with the most likely determined to be that with the metal ion bound through the nitrogen donors of the thiazoles and one deprotonated amide. For HI-lissoclinamide 5 the calculations suggest that the CuII ion is bound in a bidentate manner by the oxazoline nitrogen atom and one deprotonated amide nitrogen atom, with the S donor of the thiazole not involved in coordination. Along with evidence of copper binding these systems also bound halide ions. Evaluation of the anti-cancer properties demonstrated that the biological activity of HI-lissoclinamide 5 against T24 bladder cells was eleven-fold lower as compared to natural lissoclinamide 5. Addition of a CuII salt had no effect on the activity of lissoclinamide 5. Overall, this comprehensive study of the HI concept has demonstrated that small changes propagate dramatic effects in complexation, halide binding, and biological activity.

Total Synthesis of Plusbacin A3 and Its Dideoxy Derivative Using a Solvent-Dependent Diastereodivergent Joullié-Ugi Three-Component Reaction

Full details of our synthetic studies toward plusbacin A3 (1), which is a depsipeptide with antibacterial activity, and its dideoxy derivative are described. To establish an efficient synthetic route of 1, a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) was used to construct trans-Pro(3-OH) in a small number of steps. Two strategies were investigated toward the total synthesis. In the first synthetic strategy, the key steps were the trans-selective JU-3CR and a macrolactonization at the final stage of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3-hexafluoroisopropanol provided the trans products, and the coupling of the fragments to prepare the macrocyclization precursor proceeded smoothly. However, attempts toward the macrolactonization did not provide the desired product. Then, the second strategy that included esterification in an initial stage was investigated. Methods for constructing trans-Pro(3-OH) were examined using a convertible isocyanide, which could be converted to a carboxylic acid required for the following amidation. Ester bond formation was achieved through an intermolecular coupling using a hydroxyl-Asp derivative and the corresponding alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization of the linear peptide gave the cyclic depsipeptide, and then the global deprotection accomplished the total synthesis of 1 and its dideoxy derivative.

Inversion of the Side-Chain Stereochemistry of Indvidual Thr or Ile Residues in a Protein Molecule: Impact on the Folding, Stability, and Structure of the ShK Toxin

ShK toxin is a cysteine-rich 35-residue protein ion-channel ligand isolated from the sea anemone Stichodactyla helianthus. In this work, we studied the effect of inverting the side chain stereochemistry of individual Thr or Ile residues on the properties of the ShK protein. Molecular dynamics simulations were used to calculate the free energy cost of inverting the side-chain stereochemistry of individual Thr or Ile residues. Guided by the computational results, we used chemical protein synthesis to prepare three ShK polypeptide chain analogues, each containing either an allo-Thr or an allo-Ile residue. The three allo-Thr or allo-Ile-containing ShK polypeptides were able to fold into defined protein products, but with different folding propensities. Their relative thermal stabilities were measured and were consistent with the MD simulation data. Structures of the three ShK analogue proteins were determined by quasi-racemic X-ray crystallography and were similar to wild-type ShK. All three ShK analogues retained ion-channel blocking activity.

Total Synthesis and Antibacterial Investigation of Plusbacin A3

The total synthesis of plusbacin A3 (1) has been accomplished using a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) as a key step. Two trans-3-hydroxy-l-proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A3. Investigating the antibacterial activity of 1 compared with that of its dideoxy analogue revealed that the threo-β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance in S. aureus against plusbacin A3.