16979-93-4Relevant articles and documents
Chemical predisposition in synthesis: application to the preparation of the pyrrolidine natural products, plakoridines A and B
Etchells, Laura L.,Helliwell, Madeleine,Kershaw, Neil M.,Sardarian, Ali,Whitehead, Roger C.
, p. 10914 - 10927 (2006)
The pyrrolidine natural products, plakoridines A and B, as well as an array of unnatural analogues, have been prepared using a five-step synthetic sequence modelled on a biogenetic theory. The key transformation involves a 'Mannich/Michael/internal-redox'
Selective construction of alkaloid scaffolds by alcohol-based direct and mild aerobic oxidative Pictet-Spengler reactions
Han, Feng,Li, Huan,Liu, Haicheng,Liu, Jianping,Xu, Qing
supporting information, p. 7079 - 7085 (2020/10/02)
Employing TBN/TEMPO as the catalysts and oxygen as the oxidant, the biologically and pharmaceutically significant tetrahydro-β-carboline and β-carboline alkaloid scaffolds that used to be obtained by multi-step processes can now be selectively obtained in only one-stepviadirect aerobic oxidative Pictet-Spengler reactions of tryptamines with alcohols under mild conditions, with water generated as the byproduct. In this reaction, TBN/TEMPO was interestingly found to be able to facilitate the cyclization step of the whole reaction. This method tolerates a variety ofC- andN-substituted tryptamines, and both the more reactive benzylic and allylic alcohols and the less reactive aliphatic alcohols. This method can also be extended to dihydro-β-carboline synthesis and applied to the more available and more economical tryptophan for β-carboline synthesis, revealing its broad substrate scope and potential in synthetic applications.
Ruthenium Catalyzed Tandem Pictet-Spengler Reaction
Cherepakhin, Valeriy,Nalikezhathu, Anju,Williams, Travis J.
supporting information, (2020/07/15)
We report a pyridyl-phosphine ruthenium(II) catalyzed tandem alcohol amination/Pictet-Spengler reaction sequence to synthesize tetrahydro-β-carbolines from an alcohol and tryptamine. Our conditions use a Lewis acid cocatalyst, In(OTf)3, that is compatible with typically base catalyzed amination and an acid catalyzed Pictet-Spengler cyclization. This method proceeds well with benzylic alcohols, heterocyclic carbinols, and aliphatic alcohols. We also show how combining this reaction with a subsequent cycloamination enables a direct synthesis of tetracyclic alkaloids like harmicine.
Asymmetric Total Synthesis of (-)-Arborisidine and (-)-19-epi-Arborisidine Enabled by a Catalytic Enantioselective Pictet-Spengler Reaction
Andres, Rémi,Wang, Qian,Zhu, Jieping
supporting information, p. 14276 - 14285 (2020/09/15)
A five-step total synthesis of arborisidine, a caged pentacyclic monoterpene indole alkaloid, has been accomplished in both racemic and enantioselective manners. The synthesis features the following three key steps: (a) a regioselective Pictet-Spengler reaction of tryptamine with 2,3-pentanedione; (b) a chemo-and stereoselective intramolecular oxidative cyclization; and (c) a complexity-generating aza-Cope/Mannich cascade followed by in situ oxidation and epimerization. A chiral pyrenylpyrrolidino-squaramide catalyzed enantioselective Pictet-Spengler reaction between tryptamine and 2,3-pentanedione is subsequently uncovered, allowing us to develop a five-step asymmetric synthesis of (-)-Arborisidine, an enantiomer of the natural substance. Both (±)-19-epi-Arborisidine and (-)-19-epi-Arborisidine are also synthesized, which undergo epimerization at room temperature in the presence of aqueous 2 N KOH to (±)-Arborisidine and (-)-Arborisidine, respectively. The 19-epi-isomer is also partially epimerized to arborisidine upon preparative TLC purification (eluent: MeOH/CHCl3 saturated with NH3) and equilibrium studies indicate that arborisidine is thermodynamically more stable than its 19-epimer. In line with Kam's biosynthesis proposal and their purification protocol, we suspect that 19-epi-Arborisidine could also be a natural product.
Metal free one pot synthesis of Β-carbolines via a domino Pictet-Spengler reaction and aromatization
Ramu,Srinath,kumar, A. Aswin,Baskar,Ilango,Balasubramanian
, p. 86 - 93 (2019/02/27)
A convenient and efficient metal free, atom economical flexible synthesis of β-carbolines involving a domino Pictet-Spengler reaction and aromatization in oxygen atmosphere in N-methyl-2-pyrollidone (NMP) is described. Variety of aryl, heteroaryl and aliphatic aldehydes were found to be good substrates for this methodology. Several β-carbolines (6a-6t) and β-carboline methyl esters (7a-7e) were synthesized using this methodology.The same reaction carried out in argon atmosphere in the presence of catalytic amount of acid in NMP furnished, tetrahydro-β-carbolines (4a-4g).
5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines
Toro-Sazo, Miguel,Cassels, Bruce K.,Brea, José,Loza, María I.,Cimadevila, Marta
, (2019/01/25)
The last fifteen years have seen the emergence and overflow into the drug scene of “superpotent” N-benzylated phenethylamines belonging to the “NBOMe” series, accompanied by numerous research articles. Although N-benzyl substitution of 5-methoxytryptamine is known to increase its affinity and potency at 5-HT2 receptors associated with psychedelic activity, N-benzylated tryptamines have been studied much less than their phenethylamine analogs. To further our knowledge of the activity of N-benzyltryptamines, we have synthesized a family of tryptamine derivatives and, for comparison, a few 5-methoxytryptamine analogs with many different substitution patterns on the benzyl moiety, and subjected them to in vitro affinity and functional activity assays vs. the human 5-HT2 receptor subtypes. In the binding (radioligand displacement) studies some of these compounds exhibited only modest selectivity for either 5-HT2A or 5-HT2C receptors suggesting that a few of them, with affinities in the 10–100 nanomolar range for 5-HT2A receptors, might presumably be psychedelic. Unexpectedly, their functional (calcium mobilization) assays reflected very different trends. All of these compounds proved to be 5-HT2C receptor full agonists while most of them showed low efficacy at the 5-HT2A subtype. Furthermore, several showed moderate-to-strong preferences for activation of the 5-HT2C subtype at nanomolar concentrations. Thus, although some N-benzyltryptamines might be abuse-liable, others might represent new leads for the development of therapeutics for weight loss, erectile dysfunction, drug abuse, or schizophrenia.
Asymmetric Induction and Enantiodivergence in Catalytic Radical C-H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution
Lang, Kai,Torker, Sebastian,Wojtas, Lukasz,Zhang, X. Peter
supporting information, p. 12388 - 12396 (2019/08/20)
Control of enantioselectivity remains a major challenge in radical chemistry. The emergence of metalloradical catalysis (MRC) offers a conceptually new strategy for addressing this and other outstanding issues. Through the employment of D2-symmetric chiral amidoporphyrins as the supporting ligands, Co(II)-based MRC has enabled the development of new catalytic systems for asymmetric radical transformations with a unique profile of reactivity and selectivity. With the support of new-generation HuPhyrin chiral ligands whose cavity environment can be fine-tuned, the Co-centered d-radicals enable to address challenging issues that require exquisite control of fundamental radical processes. As showcased with asymmetric 1,5-C-H amination of sulfamoyl azides, the enantiocontrol of which has proven difficult, the judicious use of HuPhyrin ligand by tuning the bridge length and other remote nonchiral elements allows for controlling both the degree and sense of asymmetric induction in a systematic manner. This effort leads to successful development of new Co(II)-based catalytic systems that are highly effective for enantiodivergent radical 1,5-C-H amination, producing both enantiomers of the strained five-membered cyclic sulfamides with excellent enantioselectivities. Detailed deuterium-labeling studies, together with DFT computation, have revealed an unprecedented mode of asymmetric induction that consists of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution.
A Base and Solvent-Free Ruthenium-Catalyzed Alkylation of Amines
Celaje, Jeff Joseph A.,Zhang, Xingyue,Zhang, Forrest,Kam, Lisa,Herron, Jessica R.,Williams, Travis J.
, p. 1136 - 1142 (2017/08/09)
A (pyridyl)phosphine-ligated ruthenium(II) catalyst is reported for the chemoselective benzylic N-alkylation of amines, via a hydrogen-borrowing mechanism. The catalyst operates under mild conditions, neat, and without a base or other additive. These conditions offer remarkable functional group compatibility for applications in organic synthesis, including reactions involving phenols and anilines, which are very difficult to achieve. Mechanistic studies suggest that, unlike other catalysts for this reaction, the redox steps are fast and reversible while imine formation is slow. We perceive that this is the origin of the selectivity realized with these reaction conditions.
Homologation of α-aryl amino acids through quinone-catalyzed decarboxylation/Mukaiyama-Mannich addition
Haugeberg, Benjamin J.,Phan, Johnny H.,Liu, Xinyun,O'Connor, Thomas J.,Clift, Michael D.
supporting information, p. 3062 - 3065 (2017/03/17)
A new method for amino acid homologation by way of formal C-C bond functionalization is reported. This method utilizes a 2-step/1-pot protocol to convert α-amino acids to their corresponding N-protected β-amino esters through quinone-catalyzed oxidative decarboxylation/in situ Mukaiyama-Mannich addition. The scope and limitations of this chemistry are presented. This methodology provides an alternative to the classical Arndt-Eistert homologation for accessing β-amino acid derivatives. The resulting N-protected amine products can be easily deprotected to afford the corresponding free amines.
Synthesis, in vitro antibacterial activities of a series of 3-N-substituted canthin-6-ones
Dai, Jiang-Kun,Dan, Wen-Jia,Li, Na,Du, Hong-Tao,Zhang, Ji-Wen,Wang, Jun-Ru
supporting information, p. 580 - 583 (2016/01/09)
An improved synthetic route of canthin-6-one was accomplished. To further enhance the antibacterial potency and improve water solubility, a series of 3-N-alkylated and 3-N-benzylated canthin-6-ones were designed and synthesized, and their in vitro antibacterial activities were evaluated. A clear structure-activity relationship with peak minimal inhibitory concentration (MIC) values of 0.98 (μg·mL-1) was investigated. Particularly, compounds 6i-r and 6t were found to be the most potent compounds with minimal inhibitory concentration (MIC) values lower than 1.95 (μg·mL-1) against Staphylococcus aureus.
