96929-02-1

Usage

Uses

Used in Pharmaceutical Industry:
BOC-L-VALINE THIOAMIDE is used as an intermediate in the synthesis of QZ59S-SSS (Q990000), a potential inhibitor of human P-glycoprotein. This makes it a valuable compound for improving the efficacy of cancer chemotherapy, as it can help overcome multidrug resistance in cancer cells by inhibiting the efflux pump mechanism.

Upstream product

• 35150-08-4 Boc-Val-NH₂ 
• 24424-99-5 di-tert-butyl dicarbonate 
• 66866-46-4 C₁₅H₂₇NO₆ 
• 3014-80-0 (S)-2-amino-3-methylbutanamide hydrochloride 
• 13734-41-3 t-Boc-L-valine 
• 98807-40-0 Boc-Val-O-COOEt 
• 72-18-4 L-valine 

Downstream Products

• 1609138-30-8 [1-(4-{1-[4-(2,4-dimethoxybenzylcarbamoyl)thiazol-2-yl]-(S)-2-methylpropylcarbamoyl}thiazol-2-yl)-(S)-2-methylpropyl]carbamicacid tert-butyl ester 

Relevant academic research and scientific papers

Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles

Oxazoles and thiazoles are commonly found moieties in nonribosomal peptides (NRPs) and ribosomally synthesized post-translationally modified peptides (RiPPs), which are important biomolecules present in the environment and in natural waters. From previous studies, they seem susceptible to oxidation by singlet oxygen (1O2); therefore, we designed and synthesized model oxazole- and thiazole-peptides and measured their1O2 bimolecular reaction rate constants, showing slow photooxidation under environmental conditions. We reasoned their stability through the electron-withdrawing effect of the carboxamide substituent. Reaction products were elucidated and support a reaction mechanism involving cycloaddition followed by a series of rearrangements. The first1O2 bimolecular reaction rate constant for a RiPP, the thiazole-containing peptide Aerucyclamide A, was measured and found in good agreement with the model peptide's rate constant, highlighting the potential of using model peptides to study the transformations of other environmentally relevant NRPs and RiPPs.

RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles

The established cytotoxic agent RITA contains a thiophene-furan-thiophene backbone and two terminal alcohol groups. Herein we investigate the effect of using thiazoles as the backbone in RITA-like molecules and modifying the terminal groups of these trithiazoles, thereby generating 41 unique structures. Incorporating side chains with varied steric bulk allowed us to investigate how size and a stereocenter impacted biological activity. Subjecting compounds to growth inhibition assays on HCT-116 cells showed that the most potent compounds 7d, 7e, and 7h had GI50 values of 4.4, 4.4, and 3.4 μM, respectively, versus RITA (GI50 of 800 nM). Analysis of these compounds in apoptosis assays proved that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated that it acts via a different mechanism of action to that of RITA. RITA suppressed Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an alternative mechanism independent of p53.

Isolation, Structure Elucidation, Biosynthesis, and Synthesis of Antalid, a Secondary Metabolite from Polyangium species

The isolation, structure elucidation, and synthesis of antalid (1), a novel secondary metabolite from Polyangium sp., is described herein. The structure elucidation of 1 was performed with the aid of mass spectrometry, high field NMR experiments, and crystal structure analysis. The absolute configuration of antalid was confirmed through the Mosher ester method and ultimately by total synthesis. In addition, the biosynthetic origin of this hybrid PKS-NRPS natural product was unraveled by the in silico analysis of its biosynthetic gene cluster.

Design, synthesis, and biological evaluation of (S)-valine thiazole-derived cyclic and noncyclic peptidomimetic oligomers as modulators of human P-glycoprotein (ABCB1)

Multidrug resistance caused by ATP binding cassette transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure in cancer chemotherapy. Previously, selenazole-containing cyclic peptides were reported

Synthesis of the thiazole-thiazoline fragment of largazole analogues

The thiazole - thiazoline fragment of the marine natural product largazole, a potent histone deacetylase 1 inhibitor, has been synthesized in five steps. The methodology provides rapid access to thiazole-4-carbonitrile, thiazole-4-carbimidate, thiazole -

Total synthesis of the thiazolyl peptide GE2270 A

(Chemical Equation Presented) When one door closes, another opens: In the synthesis of the thiazolyl peptide GE2270 A (1), the bonds labeled I and II at the pyridine core were established by two consecutive cross-coupling reactions. Amide bond formation (

Holzapfel-Meyers-Nicolaou modification of the Hantzsch thiazole synthesis

Modified conditions for Hantzsch thiazole synthesis provides valine- and threonine-derived thiazoles without significant loss of optical purity. This two- or three-step procedure proceeds by the cyclocondensation of the corresponding thioamide under basic conditions, according to modified methods of Meyers and Holzapfel. The hydroxythiazoline intermediate is then dehydrated by treatment with trifluoroacetic anhydride-pyridine, followed by triethylamine, according to Nicolaou's procedure. Solvolysis of the trifluoroacetamide derivative produced in this process can be affected with sodium ethoxide in ethanol to give a reliable method for the stereoselective synthesis of functionalised thiazole building blocks in high yield. Georg Thieme Verlag Stuttgart.

Structure-based design of agents targeting the bacterial ribosome

Rational structure-based drug design has been applied to the antibiotic thiostrepton, in an attempt to overcome some of its' limitations. The identification of a proposed binding fragment allowed construction of a number of key fragments, which were derivatised to generate a library of potential antibiotics. These were then evaluated to determine their ability to bind to the L11 binding domain of the prokaryotic ribosome and inhibit bacterial protein translation.

Convenient syntheses of fragment B and linear main skeleton [fragment A-B-C'] derivatives of an antibiotic, GE 2270 A

Convenient synthesis of the protected linear precursor [Fragment A-B-C'] of a macrocyclic antibiotic, GE 2270 A, was achieved by coupling of a 2,3,6-tristhiazolyl-substituted pyridine skeleton [Fragment A-C'] with a thiazoloyl-thiazole segment [Fragment B]. The Fragment B was synthesized from an appropriate thioamide and β-bromo-α-oxoalkanoate, the latter of which was first derived by consecutive β-bromination and hydrolytic removal of the α-(N-Boc)amino group of an α-dehydroamino acid ester.