52448-16-5

Usage

Uses

Used in Biological Spectroscopy and Microscopy:
4-BROMO-L-TRYPTOPHAN is used as a key component in the synthesis of fluorescent proteins, which are essential for biological spectroscopy and microscopy. The application reason is its ability to enhance the visualization and analysis of cellular processes and structures, contributing to a better understanding of biological systems.
Used in Pharmaceutical Research:
4-BROMO-L-TRYPTOPHAN is used as a research tool for the development of new drugs and therapies. The application reason is its potential to serve as a building block for novel pharmaceutical compounds, which can be tailored to target specific biological pathways or receptors.
Used in Chemical Synthesis:
4-BROMO-L-TRYPTOPHAN is used as an intermediate in the chemical synthesis of various compounds, including those with potential applications in the pharmaceutical, agrochemical, and materials science industries. The application reason is its unique chemical properties, which allow for the creation of a diverse range of products with specific functionalities.

Upstream product

• 252026-08-7 N-acetyl-4-bromo-DL-tryptophan 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 52488-36-5 4-bromo-1H-indole 
• 56-45-1 L-serin 
• 691885-26-4 dl-4-bromo-N-(tert-butoxycarbonyl)tryptophan 
• 98600-34-1 4-bromo-1H-indole-3-carbaldehyde 
• 162893-62-1 (S)-4-bromo-N-(tert-butoxycarbonyl)-1-tosyltryptophan methyl ester 
• 691885-32-2 (S)-4-bromo-N-(tert-butoxycarbonyl)tryptophan methyl ester 

Downstream Products

• 73-22-3 L-Tryptophan 
• 33062-26-9 (-)-trans-clavicipitic acid 

Relevant academic research and scientific papers

An Obligate Peptidyl Brominase Underlies the Discovery of Highly Distributed Biosynthetic Gene Clusters in Marine Sponge Microbiomes

Marine sponges are prolific sources of bioactive natural products, several of which are produced by bacteria symbiotically associated with the sponge host. Bacteria-derived natural products, and the specialized bacterial symbionts that synthesize them, are not shared among phylogenetically distant sponge hosts. This is in contrast to nonsymbiotic culturable bacteria in which the conservation of natural products and natural product biosynthetic gene clusters (BGCs) is well established. Here, we demonstrate the widespread conservation of a BGC encoding a cryptic ribosomally synthesized and post-translationally modified peptide (RiPP) in microbiomes of phylogenetically and geographically dispersed sponges from the Pacific and Atlantic oceans. Detection of this BGC was enabled by mining for halogenating enzymes in sponge metagenomes, which, in turn, allowed for the description of a broad-spectrum regiospecific peptidyl tryptophan-6-brominase which possessed no chlorination activity. In addition, we demonstrate the cyclodehydrative installation of azoline heterocycles in proteusin RiPPs. This is the first demonstration of halogenation and cyclodehydration for proteusin RiPPs and the enzymes catalyzing these transformations were found to competently interact with other previously described proteusin substrate peptides. Within a sponge microbiome, many different generalized bacterial taxa harbored this BGC with often more than 50 copies of the BGC detected in individual sponge metagenomes. Moreover, the BGC was found in all sponges queried that possess high diversity microbiomes but it was not detected in other marine invertebrate microbiomes. These data shed light on conservation of cryptic natural product biosynthetic potential in marine sponges that was not detected by traditional natural product-to-BGC (meta)genome mining.

Preparation method of non-natural L - tryptophan derivative

The invention discloses a preparation method of a non-natural L - tryptophan derivative, which is sequentially subjected to formylation by adopting a cheap and easily available substituted indole compound as a raw material. Cyclization, ring opening, asym

General synthesis of unnatural 4-, 5-, 6-, and 7-bromo-D-tryptophans by means of a regioselective indole alkylation

A general two-step approach to enantiopure bromotryptophans from unprotected bromoindoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with cyclic sulfamidates derived from enantiopure D-serine to form 4-, 5-, 6-, or 7-bromo-D-tryptophan and some other halogenated tryptophans in moderate yields but with complete regioselectivity. The bromotryptophan derivatives were deprotected using mild conditions.

De novo Biosynthesis of “Non-Natural” Thaxtomin Phytotoxins

Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to “non-natural” product target compounds.

ANTIBACTERIAL COMPOUNDS

Novel compounds having antimicrobial activitiy, in particular against Pseudomonas aeruginosa, Burkholderia cepaciaand/or Clostridium difficile, and a pharmaceutical composition containing the novel compound.

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.

Unlocking Reactivity of TrpB: A General Biocatalytic Platform for Synthesis of Tryptophan Analogues

Derivatives of the amino acid tryptophan (Trp) serve as precursors for the chemical and biological synthesis of complex molecules with a wide range of biological properties. Trp analogues are also valuable as building blocks for medicinal chemistry and as tools for chemical biology. While the enantioselective synthesis of Trp analogues is often lengthy and requires the use of protecting groups, enzymes have the potential to synthesize such products in fewer steps and with the pristine chemo- and stereoselectivity that is a hallmark of biocatalysis. The enzyme TrpB is especially attractive because it can form Trp analogues directly from serine (Ser) and the corresponding indole analogue. However, many potentially useful substrates, including bulky or electron-deficient indoles, are poorly accepted. We have applied directed evolution to TrpB from Pyrococcus furiosus and Thermotoga maritima to generate a suite of catalysts for the synthesis of previously intractable Trp analogues. For the most challenging substrates, such as nitroindoles, the key to improving activity lay in the mutation of a universally conserved and mechanistically important residue, E104. The new catalysts express at high levels (>200 mg/L of Escherichia coli culture) and can be purified by heat treatment; they can operate up to 75 °C (where solubility is enhanced) and can synthesize enantiopure Trp analogues substituted at the 4-, 5-, 6-, and 7-positions, using Ser and readily available indole analogues as starting materials. Spectroscopic analysis shows that many of the activating mutations suppress the decomposition of the active electrophilic intermediate, an amino-acrylate, which AIDS in unlocking the synthetic potential of TrpB.

Natural and directed biosynthesis of communesin alkaloids

A role for tryptophan, acetate, mevalonate and methionine in the biosynthesis of communesins A and B, novel structurally-related and biologically-active Penicillium metabolites, has been established by isotopic labelling techniques. The incorporation of 14C-tryptamine has also been demonstrated. dl-2-13C-tryptophan specifically enriched two carbon atoms in the 13C NMR spectrum, thereby defining the intra-molecular arrangement of the two tryptophan-derived moieties. Feeding differentially labelled precursors during communesin production showed that tryptophan and methionine are involved early in the biosynthesis and that mevalonate provides an isoprene which is added later. A biosynthetic pathway involving an early precursor based on tryptophan is proposed. Indole-N-( 13C-methyl) tryptophan was not incorporated into communesins implying that N-methylation of tryptophan is not the first step of the communesin biosynthetic pathway. During deamination of indole-N-(13C-methyl) tryptophan to 1-13C-methylindole-3-carboxylic acid communesin biosynthesis was inhibited. Of several halogenated indoles tested for directed biosynthesis, only dl-6-fluoro-tryptophan and 6-fluoro-tryptamine caused accumulation of the corresponding monofluoro-analogues of communesins A and B.

Total synthesis without protection: Three-step synthesis of optically active clavicipitic acids by a biomimetic route

A three-step synthesis of a mixture of optically active cis- and frans-clavicipitic acids 6, which are ergot alkaloids, was achieved, starting from 4-bromoindole (7) and dl-serine (dl-2). This short synthesis was made possible by omitting the protection and deprotection steps from the synthetic route. The key step was the spontaneous cyclization of 4-vinyltryptophan (10) formed from the Heck reaction of 4-bromotryptophan (8) with 2-methyl-3-buten-2- ol (9) in aqueous media. During this investigation, we also found that the palladium-catalyzed reaction of 8 with 9 showed an interesting pH dependence; under strongly basic conditions, the Heck reaction occurred to give a C 4-vinylated product 10, whereas an N-allylated product 19b was formed under neutral or weakly basic conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

An efficient method of synthesizing optically pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan methyl ester, a key intermediate in the synthesis of optically active ergot alkaloids

Optically pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan methyl ester (D-4), a key intermediate in the synthesis of optically active ergot alkaloids such as chanoclavine-I (7) and costaclavine (8), was prepared from N-acetyl-4-bromo-D-tryptophan (D-11) obtained from 4-bromoindole (9) and DL-serine (10) in two steps.