Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)-Lundurine?A.

ABSTRACT: A novel vinylogous Pictet-Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine?A.

SUBMITTER: Nash A

PROVIDER: S-EPMC6392010 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)-Lundurine A.

Nash Aaron A Qi Xiangbing X Maity Pradip P Owens Kyle K Tambar Uttam K UK

Angewandte Chemie (International ed. in English) 20180504 23

A novel vinylogous Pictet-Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A. ...[more]

PMID: 29663602

Similar Datasets

Lessons from the Total Synthesis of (±) Phalarine: Insights Into the Mechanism of the Pictet-Spengler Reaction.

Project description:The furanobisindole alkaloid, phalarine, possesses a unique structural framework within the alkaloid family of natural products. Our laboratory recently disclosed the racemic total synthesis of phalarine, featuring an efficient azaspiroindolenine rearrangement; this achievement is revisited in detail. Upon completion of the first-generation total synthesis, we explored some interesting mechanism-level issues with regard to the key azaspiroindolenine rearrangement. These investigations provided valuable insights into the mechanism of racemization during the azaspiroindolenine rearrangement en route to synthetic phalarine. In addition, in the course of these studies, we demonstrated the Pictet-Spengler capture reaction for C(2)-aryl indoles, and successfully isolated the elusive azaspiroindolenine intermediate of the Pictet-Spengler reaction. Key insights into the remarkably subtle stereoelectronics that govern this rearrangement for C(2)-arylated indoles are discussed.

| S-EPMC2920150 | biostudies-other

Total synthesis of enantiopure phalarine via a stereospecific Pictet-Spengler reaction: traceless transfer of chirality from L-tryptophan.

Project description:An appropriately constructed 2-substituted derivative of l-tryptophan undergoes conversion to a prephalarine structure in a single step. The reaction occurs in a diastereoselective fashion, leading shortly thereafter to the naturally occurring version of the alkaloid phalarine.

| S-EPMC2895623 | biostudies-literature

Enantioselective Pictet-Spengler Reactions of Isatins for the Synthesis of Spiroindolones.

Project description:The condensation cyclization between isatins and 5-methoxy tryptamine catalyzed by chiral phosphoric acids provides spirooxindole tetrahydro-?-carboline products in excellent yields (up to 99%) and enantioselectivity (up to 98:2 er). A comparison of catalysts provides insight for the substrate scope and factors responsible for efficient catalytic activity and selectivity in the spirocyclization. Chiral phosphoric acids with different 3,3'-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration.

| S-EPMC3307811 | biostudies-literature

Highly Stereoselective Ugi/Pictet-Spengler Sequence.

Project description:Discovering novel synthetic routes for rigid nitrogen-containing polyheterocycles using sustainable, atom-economical, and efficient (= short) synthetic pathways is of high interest in organic chemistry. Here, we describe an operationally simple and short synthesis of the privileged scaffold dihydropyrrolo[1,2-a]pyrazine-dione from readily accessible starting materials. The alkaloid-type polycyclic scaffold with potential bioactivity was achieved by a multicomponent reaction (MCR)-based protocol via a Ugi four-component reaction and Pictet-Spengler sequence under different conditions, yielding a diverse library of products.

| S-EPMC9490873 | biostudies-literature

Thiourea-catalyzed enantioselective iso-Pictet-Spengler reactions.

Project description:A one-pot condensation of isotryptamines and aldehydes that affords enantiomerically enriched 4-substituted tetrahydro-γ-carbolines is reported. The reaction is induced by a chiral thiourea/benzoic acid dual catalyst system. Purification of the N-Boc-protected products by trituration or crystallization provides the optically pure tetrahydro-γ-carboline derivatives in a scalable and highly practical procedure.

| S-EPMC3206290 | biostudies-literature

Polycyclic compounds by Ugi-Pictet-Spengler sequence.

Project description:A general approach to architecturally stimulating polycyclic structures is described by a concise, two-step procedure including a Ugi MCR (multicomponent reaction) and a subsequent Pictet-Spengler reaction starting from phenylethylamine-derived isocyanides. Ten compounds are described in full experimental detail, and yields range from medium to very good. Some of the reactions run with a high degree of stereoselectivity. The compound structures resemble steroid hormones and alkaloid classes of natural products. Exemplary products have been fully reduced to their tertiary amines. As such they could potentially become interesting biological probes.

| S-EPMC3101332 | biostudies-literature

Synthesis of aza-quaternary centers <i>via</i> Pictet-Spengler reactions of ketonitrones.

Project description:Despite the array of advances that have been made in Pictet-Spengler chemistry, particularly as it relates to the synthesis of β-carboline derivatives of both natural and designed origin, the ability to use such reactions to generate aza-quaternary centers remains limited. Herein, we report a simple procedure that enables the synthesis of a variety of such products by harnessing the distinct reactivity profiles of ketonitrones as activated by commercially available acyl chlorides. Notably, the reaction process is mild, fast, and high-yielding (54-97%) for a diverse collection of substrates, including some typically challenging ones, such as indole cores with electron-deficient substituents. In addition, by deploying an acyl bromide in combination with a thiourea promoter, a catalytic, asymmetric version has been established, leading to good levels of enantioselectivity (up to 83% ee) for several ketonitrones. Finally, the resultant N-O bonds within the products can also be functionalized in several unique ways, affording valuable complementarity to existing Pictet-Spengler variants based on the use of imines.

| S-EPMC8098696 | biostudies-literature

Imaging evaluation of 5HT2C agonists, [(11)C]WAY-163909 and [(11)C]vabicaserin, formed by Pictet-Spengler cyclization.

Project description:The serotonin subtype 2C (5HT2C) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT2C full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet-Spengler cyclization with [(11)C]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT2C agonists. Both radiolabeled molecules exhibit high blood-brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet-Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers.

| S-EPMC3983360 | biostudies-literature

Total Synthesis of the Ortho-Hydroxylated Protoberberines ( S)-Govaniadine, ( S)-Caseamine, and ( S)-Clarkeanidine via a Solvent-Directed Pictet-Spengler Reaction.

Project description:The common para regioselectivity in Pictet-Spengler reactions with dopamine derivatives is redirected to the ortho position by a simple change of solvents. In combination with a chiral auxiliary on nitrogen, this ortho-selective Pictet-Spengler produced the 1-benzyltetrahydroisoquinoline alkaloids ( S)-crassifoline and ( S)-norcrassifoline and the bioactive 1,2-dioxygenated tetrahydroprotoberberine alkaloids ( S)-govaniadine, ( S)-caseamine, and ( S)-clarkeanidine with high enantiopurity. Ortho/para ratios up to 89:19 and diastereomeric ratios up to 85:15 were obtained during formation of the B-ring. The general applicability of this solvent-directed regioselectivity was demonstrated with a second Pictet-Spengler reaction as required for C-ring formation of caseamine (o/p = 14:86 in trifluoroethanol) and clarkeanidine (o/p = 86:14 in toluene).

| S-EPMC6328280 | biostudies-literature

Pictet-Spengler condensations using 4-(2-aminoethyl)coumarins.

Project description:Androgen-deprivation therapy (ADT) is only a palliative measure, and prostate cancer invariably recurs in a lethal, castration-resistant form (CRPC). Prostate cancer resists ADT by metabolizing weak, adrenal androgens to growth-promoting 5α-dihydrotestosterone (DHT), the preferred ligand for the androgen receptor (AR). Developing small-molecule inhibitors for the final steps in androgen metabolic pathways that utilize 17-oxidoreductases required probes that possess fluorescent groups at C-3 and intact, naturally occurring functionality at C-17. Application of the Pictet-Spengler condensation to substituted 4-(2-aminoethyl)coumarins and 5α-androstane-3-ones furnished spirocyclic, fluorescent androgens at the desired C-3 position. Condensations required the presence of activating C-7 amino or N,N-dialkylamino groups in the 4-(2-aminoethyl)coumarin component of these condensation reactions. Successful Pictet-Spengler condensation, for example, of DHT with 9-(2-aminoethyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one led to a spirocyclic androgen, (3R,5S,10S,13S,17S)-17-hydroxy-10,13-dimethyl-1,2,2',3',4,5,6,7,8,8',9,9',10,11,12,12',13,13',14,15,16,17-docosahydro-7'H,11'H-spiro-[cyclopenta[a]phenanthrene-3,4'-pyrido[3,2,1-ij]pyrido[4',3':4,5]pyrano[2,3-f]quinolin]-5'(1'H)-one. Computational modeling supported the surrogacy of the C-3 fluorescent DHT analog as a tool to study 17-oxidoreductases for intracrine, androgen metabolism.

| S-EPMC8009307 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data