114873-17-5

Basic information

• Product Name: BOC-5-BROMO-D-TRYPTOPHAN
• Synonyms: BOC-5-BROMO-D-TRYPTOPHAN;D-Tryptophan, 5-bromo-N-[(1,1-dimethylethoxy)carbonyl]-;Boc-D-5-BromoTryptophan
• CAS NO: 114873-17-5
• Molecular Formula: C16H19BrN2O4
• Molecular Weight: 383.24
• Mol File: 114873-17-5.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: BOC-5-BROMO-D-TRYPTOPHAN(CAS DataBase Reference)
• NIST Chemistry Reference: BOC-5-BROMO-D-TRYPTOPHAN(114873-17-5)
• EPA Substance Registry System: BOC-5-BROMO-D-TRYPTOPHAN(114873-17-5)

Safety Data

• Hazardous Substances Data: 114873-17-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research and Development:
BOC-5-BROMO-D-TRYPTOPHAN is used as a key intermediate in the synthesis of peptides and proteins for pharmaceutical research and development. Its unique structure contributes to the creation of new pharmaceuticals and bioactive compounds, enhancing the discovery of potential therapeutic agents.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, BOC-5-BROMO-D-TRYPTOPHAN is utilized as a valuable tool for modulating protein-protein interactions. Its properties make it instrumental in the design and synthesis of novel peptides that can be explored for their therapeutic effects.
Used in the Development of New Pharmaceuticals:
BOC-5-BROMO-D-TRYPTOPHAN is employed as a building block in the development of new pharmaceuticals. Its potential in creating bioactive compounds positions it as a crucial component in advancing drug discovery and innovation.
Used in Bioactive Compound Synthesis:
BOC-5-BROMO-D-TRYPTOPHAN is also used as a precursor in the synthesis of bioactive compounds, which can be further explored for their potential applications in medicine and healthcare. The versatility of BOC-5-BROMO-D-TRYPTOPHAN in peptide synthesis makes it a valuable asset in the creation of new therapeutic agents.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 6548-09-0 5-bromo-DL-tryptophan 
• 75816-15-8 N^α-acetyl-5-bromo-D,L-tryptophan 
• 6548-09-0 5-bromo-DL-tryptophan 
• 75816-19-2 (S)-7-bromo-tryptophan 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 
• 133766-35-5 ethyl 2-hydroximino-3-(5-bromoindol-3-yl)propanoate 
• 10075-50-0 5-bromo-1H-indole 
• 133766-37-7 N-Boc-5-bromo-DL-tryptophan ethyl ester 

Downstream Products

• 103343-28-8 3-(5-Bromo-1H-indol-3-ylmethyl)-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 

Relevant articles and documents

Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo

Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with 18F and their biological evaluation. 4-7-[18F]Fluorotryptophans ([18F]FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4-7-[18F]FTrps in different tumor cell lines. 4, 5-, and 6-[18F]FTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-[18F]FTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-[18F]FTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-[18F]FTrp represents a highly promising PET probe for imaging of Trp metabolism.

Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia

5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.

Preparation and evaluation of L- and D-5-[18F]fluorotryptophan as PET imaging probes for indoleamine and tryptophan 2,3-dioxygenases

Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[18F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET). Results L-5-[18F]fluorotryptophan and D-5-[18F]fluorotryptophan were synthesized by Cu(I) catalyzed [18F]fluorodeboronylation of Boc/tBu protected precursors in moderate yields (1.5?±?0.6%) sufficient for pre-clinical studies. The specific activity of the product was 407–740?GBq/μmol, radiochemical purity >99% and enantiomeric excess 90–99%. Enzymatic assay confirmed that L-5-fluorotryptophan is an IDO1 and TDO2 substrate whereas the D-isomer is not. In-vitro cell uptake experiments using CT26 cells with doxycycline-induced overexpression of human-IDO1 and human-TDO2 revealed an elevated cell uptake of L-5-[18F]fluorotryptophan upon induction of IDO1 or TDO2 enzymes compared to baseline; however, the uptake was observed only in the presence of low L-tryptophan levels in media. PET imaging experiments performed using tumor bearing mouse models expressing IDO1 at various levels (CT26, CT26-hIDO1, 17082A, 17095A) showed tumor uptake of the tracer elevated up to 8%ID/g; however, the observed tumor uptake could not be attributed to IDO1 activity in the tumor tissue. The metabolism of L- and D- isomers was markedly different in vivo, the D-isomer was excreted by a combination of hepatobiliary and renal routes, the L-isomer underwent extensive metabolism to [18F]fluoride. Conclusion The observed in vivo tumor uptake of the tracer could not be attributed to IDO1 or TDO2 enzyme activity in the tumor, presumably due to competition with endogenous tryptophan as well as rapid tracer metabolism.

Synthesis and biological evaluation of 18F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging

In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[18F]fluoropropyl)-dl- tryptophan ([18F]2-FPTRP) and 5-(3-[18F]fluoro-propyl)-dl- tryptophan ([18F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [ 18F]2-FPTRP comparable to the well established tyrosine analog O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.

Mild, Aqueous α-Arylation of Ketones: Towards New Diversification Tools for Halogenated Metabolites and Drug Molecules

The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.

Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors

The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.

5-Bromo-DL-tryptophan and Protected Intermediates for Peptide Synthesis

A convenient synthesis of 5-bromotryptophan and protected intermediates for peptide synthesis is reported.Only three steps are required to convert ethyl pyruvate into 5-bromo-tryptophan ethyl ester.

Somatostatin analogs having a substituted tryptophyl residue in position eight

Tetradecapeptides of the formula STR1 in which A represents L, D or DL 5- or 6- fluoro-, bromo-,chloro- or iodotryptophyl, or a therapeutically acceptable acid addition salt thereof, their preparation and intermediates for their preparation are disclosed. The tetradecapeptides are useful for inhibiting the release of growth hormone. Compositions and methods for their use also are disclosed.