29702-35-0

Usage

Uses

Used in Pharmaceutical Industry:
L-Tryptophan, 4-(3-methyl-2-butenyl)is used as an intermediate in the biosynthesis of ergot alkaloids, which are a group of naturally occurring compounds with significant pharmacological properties. These alkaloids, such as ergotamine and lysergic acid, have been used in the treatment of various medical conditions, including migraines, Parkinson's disease, and postpartum hemorrhage.
Used in the Synthesis of Ergot Alkaloids:
L-Tryptophan, 4-(3-methyl-2-butenyl)plays a crucial role in the biosynthesis of ergot alkaloids, which are a group of compounds with potent biological activities. These alkaloids are derived from the fungus Claviceps purpurea and have been used in the development of various pharmaceuticals due to their ability to interact with the human body's neurotransmitter systems. The unique structure of 4-Dimethylallyl-L-tryptophan allows for the efficient synthesis of these ergot alkaloids, making it an essential component in the pharmaceutical industry.

Upstream product

• 358-72-5 dimethylallyl diphosphate 
• 73-22-3 L-Tryptophan 
• 1186-30-7 3,3-dimethylallyl diphosphate triammonium salt 
• 358-71-4 isopentyl pyrophosphate 
• 388116-27-6 indole-4-boronic acid pinacol ester 
• 503-60-6 3,3-dimethyl-allyl chloride 
• 22679-02-3 dimethylallyl pyrophosphate 

Downstream Products

• 72690-85-8 (1S,3S)-1-(2-methylprop-1-en-1-yl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indole-3-carboxylic acid 
• 33062-26-9 (-)-trans-clavicipitic acid 
• 80152-02-9 (-)-aurantioclavine 

Relevant academic research and scientific papers

Elucidation of the concise biosynthetic pathway of the communesin indole alkaloids

The communesins are a prominent class of indole alkaloids isolated from Penicillium species. Owing to their daunting structural framework and potential as pharmaceuticals, communesins have inspired numerous synthetic studies. However, the genetic and biochemical basis of communesin biosynthesis has remained unexplored. Herein, we report the identification and characterization of the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We confirmed that communesin is biosynthesized by the coupling of tryptamine and aurantioclavine, two building blocks derived from L-tryptophan. The postmodification steps were mapped by targeted-gene-deletion experiments and the structural elucidation of intermediates and new analogues. Our studies set the stage for the biochemical characterization of communesin biosynthesis. This knowledge will aid our understanding of how nature generates remarkable structural complexity from simple precursors.

Total Synthesis of (-)-Clavicipitic Acid via γ,γ-Dimethylallyltryptophan (DMAT) and Chemoselective C-H Hydroxylation

The first total synthesis of natural (-)-clavicipitic acid from ?,?-dimethylallyltryptophan (DMAT), its biosynthetic precursor, is described. This is done by regio- and chemoselective, remote, nondirected C(sp3)-H hydroxylation followed by amin

Expansion of enzymatic Friedel-Crafts alkylation on indoles: Acceptance of unnatural β-unsaturated allyl diphospates by dimethylallyl-tryptophan synthases

Prenyltransferases of the dimethylallyl-tryptophan synthase (DMATS) superfamily catalyze Friedel-Crafts alkylation with high flexibility for aromatic substrates, but the high specificity for dimethylallyl diphosphate (DMAPP) prohibits their application as biocatalysts. We demonstrate here that at least one methyl group in DMAPP can be deleted or shifted to the d-position. For acceptance by some DMATS enzymes, however, a double bond must be situated at the β-position. Furthermore, the alkylation position of an analogue can differ from that of DMAPP.

A short synthesis of optically active γ,γ-dimethylallyltryptophan (DMAT)

A short synthesis (4 steps) of optically active γ,γ- dimethylallyltryptophan (1, DMAT) was accomplished from N(α)-tert- butoxycarbonyl(Boc)-4-(3-hydroxy-3-methyl-1-buten-1-yl)-1-tosyl-tryptophan methyl ester (5) prepared by Heck reaction of N(α)-Boc-4-bro

Structure and specificity of a permissive bacterial C-prenyltransferase

This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including

FgaPT2, a biocatalytic tool for alkyl-diversification of indole natural products

Aromatic prenyltransferases from natural product biosynthetic pathways display relaxed specificity for their aromatic substrates. While a growing body of evidence suggests aromatic prenyltransferases to be more tolerant towards their alkyl-donor substrates, most studies aimed at probing their donor-substrate specificity are limited to only a small set of alkyl pyrophosphate donors, restricting their broader utility as biocatalysts for synthetic applications. Here, we assess the donor substrate specificity of an l-tryptophan C4-prenyltransferase, also known as C4-dimethylallyltryptophan synthase, FgaPT2 from Aspergillus fumigatus, using an array of 34 synthetic unnatural alkyl-pyrophosphate analogues, and demonstrate FgaPT2 can catalyze the transfer of 25 of the 34 non-native alkyl groups from their corresponding synthetic alkyl-pyrophosphate analogues at N1, C3, C4 and C5 position of tryptophan in a normal and reverse manner. The kinetic studies and regio-chemical analysis of the alkyl-l-tryptophan products suggest that the alkyl-donor transfer by FgaPT2 is a function of the stability of the carbocation and the steric factors in the active site of the enzyme. Further, to demonstrate the biocatalytic utility of FgaPT2, this study also highlights the FgaPT2-catalyzed synthesis of a small set of alkyl-diversified indolocarbazole analogues. These results reveal FgaPT2 to be more tolerant to diverse non-native alkyl-donor substrates beyond their known acceptor substrate promiscuity and set the stage for its development as a novel biocatalytic tool for the differential alkylation of natural products for drug discovery and other synthetic applications.

Structure-based protein engineering enables prenyl donor switching of a fungal aromatic prenyltransferase

Microorganisms provide valuable enzyme machinery to assemble complex molecules. Fungal prenyltransferases (PTs) typically catalyse highly regiospecific prenylation reactions that are of significant pharmaceutical interest. While the majority of PTs accepts dimethylallyl diphosphate (DMAPP), very few such enzymes can use geranyl diphosphate (GPP) or farnesyl diphosphate (FPP) as donors. This catalytic gap prohibits the wide application of PTs for structural diversification. Structure-guided molecular modelling and site-directed mutagenesis of FgaPT2 from Aspergillus fumigatus led to the identification of the gatekeeping residue Met328 responsible for the prenyl selectivity and sets the basis for creation of GPP- and FPP-accepting enzymes. Site-saturation mutagenesis of the gatekeeping residue at position 328 in FgaPT2 revealed that the size of this side chain is the determining factor for prenyl selectivity, while its hydrophobicity is crucial for allowing DMAPP and GPP to bind.

Mechanistic Studies of the Protonation-Deprotonation Reactions for Type 1 and Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase

Type 1 and type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-1 and IDI-2) catalyze the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the fundamental building blocks for biosynthesis of isoprenoid compounds. Previous studies indicate that both isoforms of IDI catalyze isomerization by a protonation-deprotonation mechanism. IDI-1 and IDI-2 are sluggish enzymes with turnover times of ～10 s-1 and ～1 s-1, respectively. We measured incorporation of deuterium into IPP and DMAPP in D2O buffer for IDI-1 and IDI-2 under conditions where newly synthesized DMAPP is immediately and irreversibly removed by coupling its release to condensation with l-tryptophan catalyzed by dimethylallyltrytophan synthase. During the course of the reactions, we detected formation of d1, d2, and d3 isotopologues of IPP and DMAPP, which were formed during up to five isomerizations between IPP and DMAPP during each turnover. The patterns for deuterium incorporation into IPP show that d2-IPP is formed in preference to d1-IPP for both enzymes. Analysis of the patterns of deuterium incorporation are consistent with a mechanism involving addition and removal of protons by a concerted asynchronous process, where addition substantially precedes removal, or a stepwise process through a short-lived (a concerted asynchronous mechanism for the enzyme-catalyzed isomerizations.

Tryptophan prenyltransferases showing higher catalytic activities for Friedel-Crafts alkylation of o- and m-tyrosines than tyrosine prenyltransferases

Tryptophan prenyltransferases FgaPT2, 5-DMATS, 6-DMATSSv and 7-DMATS catalyse regiospecific C-prenylations on the indole ring, while tyrosine prenyltransferases SirD and TyrPT catalyse the O-prenylation of the phenolic hydroxyl group. In this s

Tryptophan prenyltransferases showing higher catalytic activities for Friedel-Crafts alkylation of o- and m-tyrosines than tyrosine prenyltransferases

Tryptophan prenyltransferases FgaPT2, 5-DMATS, 6-DMATSSv and 7-DMATS catalyse regiospecific C-prenylations on the indole ring, while tyrosine prenyltransferases SirD and TyrPT catalyse the O-prenylation of the phenolic hydroxyl group. In this s