Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• oxa-Pictet–Spengler reaction from 2,6-dihydroxybenzoic acid 173 and ketal aldehyde 174 as key building blocks (Figure 10). The 2,6-dihydroxybenzoic acid 173 is accessible by opening of epoxide 175 as chiron with a suitable nucleophile. The ketal aldehyde 174 would be derived from butenolide 176

• with DIBAL-H gave ketal aldehyde 181, which was then condensed with 2,6-dihydroxybenzoic acid 173 in a oxa-Pictet–Spengler reaction to form the tetracyclic core of berkelic acid. Treatment of the obtained tetracyclic salicylic acid with allyl bromide and desilyation with TBAF/AcOH provided 182. The

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• -triphenylporphyrin. The reaction of this porphyrin with 2,5-dimethoxytetrahydrofuran, followed by the reduction of the nitro group in the presence of NiCl2/NaBH4 afforded 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin. This triphenylporphyrin underwent a Pictet–Spengler cyclization after the reaction

• ]quinoxalinoporphyrins; Pictet–Spengler reaction; synthesis; Introduction Many natural porphyrins are known to play essential roles in a number of biological processes including oxygen transport [1], solar energy conservation [2][3][4] and photosynthesis [5]. Owing to the expanded π-conjugation system as well as good

• synthesis of novel meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins (4a–h) began via the Pictet–Spengler cyclization reaction [50][51] of 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (3) with various aromatic aldehydes by using 2% TFA in dichloromethane as an acidic catalyst at 0 °C for

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• cyclization of the adduct, formed by the reaction of tryptamine with appropriately substituted 1,2,3-tricarbonyl compounds or with glyoxylic acid derivatives under Pictet–Spengler conditions is also reported in literature for the syntheses of eudistomin T (1) and eudistomin S (2b). Jenkins and co-workers

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• approaches toward the synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives have been reported [29][30][31][32][33][34][35][36][37][38][39][40][41][42]: (a) Ru- and Au-catalyzed cascade reactions between 2-(1H-indol-1-yl)anilines and alkynes [34][42]. (b) AlCl3-catalyzed Pictet–Spengler reactions

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ], the isoquinoline nuevamine (96) [77] and the benzazocine magallanesine (97) [79] were isolated from different Berberidaceae species (Figure 6). Chilenine (93) was the first isoindolobenzazepine alkaloid isolated from Berberis empetrifolia in 1982. The biogenesis proceeds most likely via a Pictet

• –Spengler reaction of dopamine (99) with 4-hydroxyphenylacetaldehyde (100), both derived from L-tyrosine (98) (Scheme 11). After oxidation and O-methylation, which is carried out by S-adenosylmethionine (SAM), (S)-reticuline (101) is obtained. Oxidation of the N-methyl group to the iminium ion and

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• Pictet–Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet–Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT

• (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet–Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology

• provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet–Spengler reaction. Keywords: β-carboline; cyanuric chloride; 6-endo cyclization; Pictet–Spengler; TCT; Introduction The Pictet–Spengler reaction is an important class of name

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• -turn conformation. The synthesis is based on a diastereoselective Pictet–Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complete the tetracyclic THBC-DKP fused ring system. The presence of conformers bearing the intramolecular thirteen-membered hydrogen bond

• synthesis of peptidomimetic 1a (Scheme 1). Starting from L-tryptophan methyl ester and N-Cbz-aminoacetaldehyde dimethyl acetal [43], tetrahydro-β-carboline 2 was obtained in good yield and high diastereoselectivity (dr 70% from 1H NMR) by means of Pictet–Spengler reaction [44] and subsequent chromatographic

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

• Piyush K. Agarwal,
• Meena D. Dathi,
• Mohammad Saifuddin and
• Bijoy Kundu

Beilstein J. Org. Chem. 2012, 8, 1901–1908, doi:10.3762/bjoc.8.220

• ). After successfully accomplishing the synthesis of amino-functionalized meridianins 2, we next examined their abilities to undergo 6-endo cyclization in the presence of aldehydes (Scheme 4). Initially we treated the substrate 2a with 4-chlorobenzaldehyde using a variety of traditional Pictet–Spengler

• oxidized product (Scheme 5). After successfully establishing the strategy on 2a-c, we then decided to replace the indole nucleus by another activated nucleus such as trimethoxy- and dimethoxybenzene and designed a substrate 18 (Scheme 6) for the Pictet–Spengler reaction using a similar approach as was used

• pyrimido[5,4-c]isoquinolines 20a–l (Table 3) in 79–92% isolated yields. Conclusion In conclusion, we have developed a mild and efficient protocol for the synthesis of pyrimido[5,4-c]isoquinolones and pyrimido-β-carbolines using a modified Pictet–Spengler strategy. Our method offers a unique opportunity to

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• } under acidic conditions to produce the corresponding products in yields ranging from 54–89%. A range of aldehydes were accommodated in the Pictet–Spengler reaction, including formaldehyde (Table 1, entry 1), alkyl aldehydes (Table 1, entries 2 and 3), aryl aldehydes with electron-withdrawing and

Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine

• Jessica Baiget,
• Sabin Llona-Minguez,
• Stuart Lang,
• Simon P. MacKay,
• Colin J. Suckling and
• Oliver B. Sutcliffe

Beilstein J. Org. Chem. 2011, 7, 1407–1411, doi:10.3762/bjoc.7.164

• analogues containing the carboline heterocyclic moiety. A manganese dioxide mediated one-pot method starting with an activated alcohol and consisting of alcohol oxidation, Pictet–Spengler cyclisation, and oxidative aromatisation, offers a convenient process that allows access to β-carbolines. This one-pot

• means of either a Pictet–Spengler or a Bischler–Napieralski cyclization followed by an oxidative dehydrogenation process [13][14][15]. Inspired by nature’s example, we wished to design a synthetic route to the β-carboline scaffold, which was biomimetic and could be carried out in a single operation. One

• glycolate (1) to manganese dioxide would result in the formation of aldehyde 2. This can then undergo a condensation process with tryptamine (3) allowing the generation of imine 4. This intermediate is set up appropriately to undergo a Pictet–Spengler cyclization reaction resulting in the formation of

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• methyl ester to form the indolopiperidine motif 135 via a Pictet–Spengler reaction followed by a double condensation to install the additional diketopiperazine ring (Scheme 28) [38][39]. To achieve the high levels of cis selectivity required from the Pictet–Spengler reaction, an extensive investigation

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• followed by Pictet–Spengler cyclization. Keywords: Curtius rearrangement; Michael reaction; Pictet–Spengler cyclization; radical azidonation; Introduction Aryl-1,2,3,4-tetrahydroisoquinolines have attracted much attention from the synthetic community owing to the potential biological activities of this

• are Michael addition, radical azidonation of aldehydes [18], Curtius rearrangement, and reduction of an isocyanate intermediate followed by Pictet–Spengler cyclization. Results and Discussion Our retrosynthetic analysis of (±)-cherylline dimethyl ether (5) is depicted in Scheme 1. It can be

• anticipated that 5 could be constructed via a Pictet–Spengler ring annulation from amine 6 which, in turn, could be obtained by reduction of the corresponding isocyanate. The required isocyanate would arise from the aldehyde 7 via radical azidonation followed by Curtius reaction. Lastly, aldehyde 7 could be