Boc-D-glutamic acid-γ-tert-butyl ester
Need Assistance?
  • US & Canada:
    +
  • UK: +

Boc-D-glutamic acid-γ-tert-butyl ester

* Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients.

Category
BOC-Amino Acids
Catalog number
BAT-002717
CAS number
104719-63-3
Molecular Formula
C14H25NO6
Molecular Weight
303.40
Boc-D-glutamic acid-γ-tert-butyl ester
IUPAC Name
(2R)-5-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
Synonyms
Boc-D-Glu(OtBu)-OH; Boc-D-glutamic acid 5-tert-butyl ester
Appearance
White to off-white powder
Purity
≥ 99% (HPLC)
Density
1.121 g/cm3
Melting Point
106-109 °C
Boiling Point
449.8±40.0 °C(Predicted)
Storage
Store at 2-8°C
InChI
InChI=1S/C14H25NO6/c1-13(2,3)20-10(16)8-7-9(11(17)18)15-12(19)21-14(4,5)6/h9H,7-8H2,1-6H3,(H,15,19)(H,17,18)/t9-/m1/s1
InChI Key
YGSRAYJBEREVRB-SECBINFHSA-N
Canonical SMILES
CC(C)(C)OC(=O)CCC(C(=O)O)NC(=O)OC(C)(C)C

Boc-D-glutamic acid-γ-tert-butyl ester, a protected amino acid derivative, finds widespread utility in peptide synthesis and biochemical investigations. Here are four key applications:

Peptide Synthesis: An integral component of solid-phase peptide synthesis, Boc-D-glutamic acid-γ-tert-butyl ester acts as a shielded building block. The Boc group shields the amino function, enabling seamless elongation of the peptide chain without undesirable side reactions. This compound ensures the generation of precise and high-purity peptides, crucial for both research endeavors and therapeutic endeavors.

Drug Development: In the realm of pharmaceutical exploration, Boc-D-glutamic acid-γ-tert-butyl ester plays a pivotal role as a precursor for the creation of glutamic acid-incorporated drugs. It facilitates the targeted alteration of the glutamic acid component within diverse drug candidates, aiding in the refinement of pharmacokinetic and pharmacodynamic properties. This compound serves as a cornerstone for crafting prodrugs and active pharmaceutical ingredients with meticulously tailored chemical attributes.

Protein Structure Studies: Within the domain of protein unfolding and structural dynamics, Boc-D-glutamic acid-γ-tert-butyl ester emerges as a critical tool. By integrating it into peptides and protein fragments, researchers can delve into the function of glutamic acid in protein conformation and stability. Understanding these intricate interactions is essential for unraveling protein functionality and conceptualizing innovative protein-centric therapeutic interventions.

Bioconjugation: In the realm of biochemical research, Boc-D-glutamic acid-γ-tert-butyl ester is harnessed for crafting bioconjugates through meticulously controlled chemical processes. The ester group can be selectively unshielded to expose reactive sites for conjugation with other molecules, such as fluorescent markers or affinity tags. This application plays a pivotal role in the development of molecular probes and diagnostic agents for diverse biosensing technologies, underpinning advancements in biomedical research.

1. Reagent-free continuous thermal tert-butyl ester deprotection
Kevin P Cole, Sarah J Ryan, Jennifer McClary Groh, Richard D Miller Bioorg Med Chem. 2017 Dec 1;25(23):6209-6217. doi: 10.1016/j.bmc.2017.03.020. Epub 2017 Mar 10.
Continuous processing enables the use of non-standard reaction conditions such as high temperatures and pressures while in the liquid phase. This expands the chemist's toolbox and can enable previously unthinkable chemistry to proceed with ease. For a series of amphoteric amino acid derivatives, we have demonstrated the ability to hydrolyze the tert-butyl ester functionality in protic solvent systems. Using a continuous plug flow reactor at 120-240°C and 15-40min reaction times, no pH modification or additional reagents are needed to achieve the desired transformation. The method was then expanded to encompass a variety of more challenging substrates to test selectivity and racemization potential. The acid products were generally isolated as crystalline solids by simple solvent exchange after the deprotection reaction in good to high yield and purity.
2. A Ketone Ester Drink Lowers Human Ghrelin and Appetite
Brianna J Stubbs, Pete J Cox, Rhys D Evans, Malgorzata Cyranka, Kieran Clarke, Heidi de Wet Obesity (Silver Spring). 2018 Feb;26(2):269-273. doi: 10.1002/oby.22051. Epub 2017 Nov 6.
Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite. Methods: Following an overnight fast, subjects with normal weight (n = 15) consumed 1.9 kcal/kg of KE, or isocaloric dextrose (DEXT), in drinks matched for volume, taste, tonicity, and color. Blood samples were analyzed for BHB, glucose, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY), and a three-measure visual analogue scale was used to measure hunger, fullness, and desire to eat. Results: KE consumption increased blood BHB levels from 0.2 to 3.3 mM after 60 minutes. DEXT consumption increased plasma glucose levels between 30 and 60 minutes. Postprandial plasma insulin, ghrelin, GLP-1, and PYY levels were significantly lower 2 to 4 hours after KE consumption, compared with DEXT consumption. Temporally related to the observed suppression of ghrelin, reported hunger and desire to eat were also significantly suppressed 1.5 hours after consumption of KE, compared with consumption of DEXT. Conclusions: Increased blood ketone levels may directly suppress appetite, as KE drinks lowered plasma ghrelin levels, perceived hunger, and desire to eat.
3. Synthesis and biological evaluation of tert-butyl ester and ethyl ester prodrugs of L-γ-methyleneglutamic acid amides for cancer
Md Imdadul H Khan, et al. Bioorg Med Chem. 2023 Jan 15;78:117137. doi: 10.1016/j.bmc.2022.117137. Epub 2022 Dec 21.
In cancer cells, glutaminolysis is the primary source of biosynthetic precursors. Recent efforts to develop amino acid analogues to inhibit glutamine metabolism in cancer have been extensive. Our lab recently discovered many L-γ-methyleneglutamic acid amides that were shown to be as efficacious as tamoxifen or olaparib in inhibiting the cell growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells after 24 or 72 h of treatment. None of these compounds inhibited the cell growth of nonmalignant MCF-10A breast cells. These L-γ-methyleneglutamic acid amides hold promise as novel therapeutics for the treatment of multiple subtypes of breast cancer. Herein, we report our synthesis and evaluation of two series of tert-butyl ester and ethyl ester prodrugs of these L-γ-methyleneglutamic acid amides and the cyclic metabolite and its tert-butyl esters and ethyl esters on the three breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 and the nonmalignant MCF-10A breast cell line. These esters were found to suppress the growth of the breast cancer cells, but they were less potent compared to the L-γ-methyleneglutamic acid amides. Pharmacokinetic (PK) studies were carried out on the lead L-γ-methyleneglutamic acid amide to establish tissue-specific distribution and other PK parameters. Notably, this lead compound showed moderate exposure to the brain with a half-life of 0.74 h and good tissue distribution, such as in the kidney and liver. Therefore, the L-γ-methyleneglutamic acid amides were then tested on glioblastoma cell lines BNC3 and BNC6 and head and neck cancer cell lines HN30 and HN31. They were found to effectively suppress the growth of these cancer cell lines after 24 or 72 h of treatment in a concentration-dependent manner. These results suggest broad applications of the L-γ-methyleneglutamic acid amides in anticancer therapy.
Online Inquiry
Inquiry Basket