Design, synthesis and diversification of natural product-inspired hydantoin-fused tetrahydroazepino indoles

Barve, Indrajeet J.; Dalvi, Prashant B.; Thikekar, Tushar Ulhas; Chanda, Kaushik; Liu, Yu Li; Fang, Chiu Ping; Liu, Chia-Chen; Sun, Chung‐Ming

doi:10.1039/c5ra12063b

Cited by 14 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2015, Sun and Co‐workers reported the synthesis of hydantoin fused indole alkaloids using ethyl bromopyruvate instead of aldehydes (Scheme ) . L ‐tryptophan methyl ester on condensation with ethyl bromopyruvate in the presence of trifluoroacetic acid under microwave irradiation afforded a diastereomeric mixture of bromomethylated β‐carbolines 282 , 283 and a rearranged product 284 .…”

Section: β‐Carboline Fused Heterocycles Synthesized Via Post‐pictet‐smentioning

confidence: 99%

Post‐Pictet‐Spengler Cyclization (PPSC): A Strategy to Synthesize Polycyclic β‐Carboline‐Derived Natural Products and Biologically Active N‐Heterocycles

Singh

Kumar

Patil³

et al. 2020

Adv Synth Catal

View full text Add to dashboard Cite

Pictet-Spengler reaction is a typical condensation reaction of β-arylethylamine or Tryptamine with an aldehyde or ketone followed by ring closure to generate tetrahydroisoquinoline (THIQ) and Tetrahydro-β-carboline (THβC), respectively. Both these key skeletons represent huge range of structurally diverse naturally occurring isoquinoline and indole alkaloids. Nature has synthesized structurally complex Reserpine, Ajmalicine as well as other related alkaloids using various biosynthetic pathways via Pictet-Spengler reaction followed by post-Pictet-Spengler cyclization (PPSC) stratergy. This biosynthetic process is the short and reliable method to access diverse range of polycyclic heterocycles. Over the period of last sixty years, several researchers have synthesized complex alkaloids without highlighting the synthetic utility of the post-Pictet-Spengler cyclization strategy. We summarized the synthesis of numerous natural products and related natural product inspired heterocyclic scaffolds which follow the PPSC strategy to demonstrate its usefulness for the construction of diverse compound collection.

show abstract

Section: β‐Carboline Fused Heterocycles Synthesized Via Post‐pictet‐smentioning

confidence: 99%

Post‐Pictet‐Spengler Cyclization (PPSC): A Strategy to Synthesize Polycyclic β‐Carboline‐Derived Natural Products and Biologically Active N‐Heterocycles

Singh

Kumar

Patil³

et al. 2020

Adv Synth Catal

View full text Add to dashboard Cite

show abstract

“…Sun group developed the natural product-inspired hydantoinfused tetrahydroazepino indoles using solution phase chemistry in 2015. 39 As depicted in Scheme 18, the Pictet−Spengler cyclization of L-tryptophan methyl ester 73 with ethyl bromopyruvate 74 in TFA afforded a mixture of bromomethy-lated product 75 (1S, 3S) along with a tetrahydroazepino indoles product 76 in 1:2 ratio. However, by refluxing the bromomethylated product 75 in the presence of KI and K 2 CO 3 in CH 3 CN for 30 min, the tetrahydroazepino indoles product 76 is obtained in high yield.…”

Section: Scaffolds Via Solid-phase/fluorous-phase/ionic-liquid--phase...mentioning

confidence: 99%

“…Sun group developed the natural product-inspired hydantoin-fused tetrahydroazepino indoles using solution phase chemistry in 2015 . As depicted in Scheme , the Pictet–Spengler cyclization of l -tryptophan methyl ester 73 with ethyl bromopyruvate 74 in TFA afforded a mixture of bromomethylated product 75 (1S, 3S) along with a tetrahydroazepino indoles product 76 in 1:2 ratio.…”

Section: Synthesis Of Tetrahydro-β-carboline Scaffolds Via Solid-phas...mentioning

confidence: 99%

Application of Pictet–Spengler Reaction to Indole-Based Alkaloids Containing Tetrahydro-β-carboline Scaffold in Combinatorial Chemistry

2017

Self Cite

View full text Add to dashboard Cite

Indole-based alkaloids are well-known in the literature for their diverse biological properties. Polysubstituted optically active tetrahydro-β-carboline derivatives functionalized on C-1 position are the common structural motif in most of the indole-based alkaloids, as well as highly marketed drugs. The stereoselective Pictet-Spengler reaction is one of the currently most important synthetic techniques used for the preparation of these privileged tetrahydro-β-carboline scaffolds. To date, there are numerous research reports that have been published on the synthesis of the tetrahydro-β-carboline scaffold both on solid phase, as well as in solution phase. Moreover rapid growth has been observed for the enantioselective synthesis of tetrahydro-β-carboline scaffold using chiral organocatalysts. In this Review, efforts have been taken to shed light on the latest information available on different strategies to synthesize tetrahydro-β-carboline both on solid phase and in solution phase during the last 20 years. Furthermore, we believe that the present synthetic methodologies covered in this Review will help to improve the status of this privileged tetrahydro-β-carboline scaffold in its use for drug discovery.

show abstract

“…15 However, the synthesis of azepino [4,5-b]indoles via ring expansion was rarely reported. 16 In 2019, Oguri reported a method for constructing azepino [4,5-b]indoles by the ring expansion strategy of N-propargylated tetrahydrocarbolines (Scheme 2a). 17 In continuation of our interest in constructing azepinondoles, 18 herein, we report an efficient and convenient method for the construction of quaternary carbon azepino [4,5b]indoles by the ring enlargement reaction of tetrahydro-βcarbolines with the diazo compound.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis of Azepino[4,5-b]indole via Ring Expansion of Tetrahydro-β-carbolines Ammonium Ylide

Shen,

Lu,

Shen

et al. 2023

J. Org. Chem.

View full text Add to dashboard Cite

The formal cyclization strategy was generally used to construct azepino [4,5-b]indole. Herein, we reported a novel and expeditious protocol for the synthesis of quaternary carbon azepino[4,5-b]indole via ring expansion of ammonium ylide, which was formed by the reaction of tetrahydro-β-carbolines with the diazo compound. The easily available substrates, mild reaction conditions, and broad functional tolerance rendered this method a practical strategy that may significantly afford an efficient method of scaffold hopping in drug discovery.

show abstract

Design, synthesis and diversification of natural product-inspired hydantoin-fused tetrahydroazepino indoles

Abstract: A facile and efficient synthesis of novel oxo, thio and seleno hydantoin fused tetrahydroazepino [4,5-b]indoles was reported.

Cited by 14 publications

References 23 publications

Post‐Pictet‐Spengler Cyclization (PPSC): A Strategy to Synthesize Polycyclic β‐Carboline‐Derived Natural Products and Biologically Active N‐Heterocycles

Post‐Pictet‐Spengler Cyclization (PPSC): A Strategy to Synthesize Polycyclic β‐Carboline‐Derived Natural Products and Biologically Active N‐Heterocycles

Application of Pictet–Spengler Reaction to Indole-Based Alkaloids Containing Tetrahydro-β-carboline Scaffold in Combinatorial Chemistry

Synthesis of Azepino[4,5-b]indole via Ring Expansion of Tetrahydro-β-carbolines Ammonium Ylide

Contact Info

Product

Resources

About