Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• derivatives. Keywords: benzoxazepines; diversity-oriented synthesis; multicomponent reactions; Mitsunobu reaction; Ugi reaction; Introduction Although the classical Ugi 4-component reaction (U-4CR) leads to acyclic peptide-like compounds, post-condensation cyclizations can afford a huge variety of drug-like

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• biologically interesting heterocycles is generally target-oriented, inspired by nature or randomly directed. In all these cases the design of a synthetic sequence to produce a library of diversely substituted molecules is the first and most important step. The basic concept of diversity-oriented synthesis (DOS

• trapping is possible. After deprotonation and protodeauration the desired spiroindoline 6a is formed with the stereochemistry of two new stereocenters S. Conclusion In conclusion we have developed a diversity-oriented post-Ugi gold-catalyzed intramolecular hydroarylation domino cyclization sequence for the

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• majucin-type sesquiterpenes is described here. This strategy is based on an organocatalyzed asymmetric Robinson annulation and provides an efficient approach for a diversity-oriented synthesis of Illicium natural products that holds remarkable therapeutic potential for neurodegenerative diseases

• represents an efficient route toward a diversity-oriented synthesis of several Illicium sesquiterpenes. The enantioselective entry to these molecules is based on an organocatalyzed asymmetric Robinson annulation that allows access to the enantiomerically enriched bicyclic motif 8 from achiral diketone 11

• the way for a diversity-oriented synthesis. For example, a Mn(III) promoted C-2 allylic oxidation [24][101][102] would provide a C-2 oxygenated functionality. Similarly, C-10 α-substitution would provide a large diversity of neurotrophic analogues based on our recent findings [26]. Conclusion We

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• ; diversity-oriented synthesis; metathesis; Introduction Our collective understanding of the biological relevance of chemical space has been shaped, in large part, by the historic exploration of chemical space by chemical synthesis (and biosynthesis) [1]. The scaffolds of known bioactive small molecules, in

• diversity-oriented synthesis [11][12][13] has emerged with the specific aim of populating screening collections with diverse and novel small molecules. We have previously developed a robust approach for the synthesis of skeletally diverse small molecules (Scheme 1) [14]. The approach relied on the synthesis

• (Table 4) were obtained after removal of the fluorous tag by desilylation. Conclusion Metathesis is an extremely powerful reaction for diversity-oriented synthesis. It was demonstrated that metathesis substrates could be assembled efficiently from triplets of building blocks. Thereafter, metathesis

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• (Figure 5), and they have investigated their catalytic activities in asymmetric alkylation reactions for producing enantiomerically enriched amino acids. The synthesis of these quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition of

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• . This fact suggests that 1 does not act just by engaging bacterial membranes as most antibacterial peptides do [49], but that it may bind to a specific target. Conclusion These results highlight the usefulness of the Ugi-4CR for the diversity-oriented synthesis of natural N-methyl peptides, such as

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• as pharmacological probes and as starting points for drug-discovery campaigns, has primarily fuelled this interest, while enabling technologies, such as diversity-oriented synthesis (DOS), have improved access to small-molecule libraries [1][2][3][4][5]. Compounds containing a γ-lactam moiety have

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

• interested in probes of these targets. Keywords: β-carboline; biological activity; chemical diversity; diversity-oriented synthesis; in silico screening; Introduction Identification of a comprehensive set of small organic molecules capable of selectively modifying the function of biological targets

• exhibit acceptable calculated physical–chemical properties in accordance with Lipinski’s rule of five (Figure 2) [9][10]. These favorable properties and structural novelty make these valuable candidates for deposition in the MLSCN for biological activity evaluation. Diversity-oriented synthesis (DOS) has

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• substructures and subsequent intramolecular cyclization between these substructures to form the fused skeletons (Figure 1c). As a pioneering approach to shape the foundation of the “Build-Couple-Pair” (B/C/P) strategy [7][8][9][10][11][12][13][14][15] for diversity-oriented synthesis [16][17], a synthetic

• composed of indole (red) and piperidine (blue) groups; (c) divergent cyclizations to generate scaffold variations as an illustration of the “Build-Couple-Pair” strategy in diversity-oriented synthesis. (a) Synthetic plans based on modular assembly and divergent cyclizations leading to fused skeletons; (b

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• materials and their subsequent transformation into complex molecular architectures. As such, it is becoming recognised as an enabling technology for diversity-oriented synthesis. Herein, we provide a thorough account of our work combining two-directional synthesis with diversity-oriented synthesis, with

• particular reference to the synthesis of polycyclic alkaloid scaffolds. Keywords: alkaloids; cascade reactions; chemical diversity; diversity-oriented synthesis; Lewis acid catalysis; two-directional synthesis; Introduction Diversity-oriented synthesis (DOS) aims to prepare structurally diverse compound

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• , Beijing 100871, China 10.3762/bjoc.8.94 Abstract Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure–activity

• relationship of this important class of hedgehog-pathway inhibitors. Keywords: chemical diversity; diversity-oriented; hedgehog pathway; inhibitor; Sant-75; synthesis; Introduction The Hedgehog (Hh) signaling pathway plays an essential role in embryonic development and adult tissue homeostasis in metazoans

Recent developments in chemical diversity

• John A. Porco Jr

Beilstein J. Org. Chem. 2012, 8, 827–828, doi:10.3762/bjoc.8.92

• John A. Porco Jr Boston University, Department of Chemistry, 590 Commonwealth Avenue, Boston MA 02215, USA 10.3762/bjoc.8.92 Keywords: chemical diversity; Diversity-oriented synthesis (DOS) is an important field involving the synthesis of libraries of diverse small molecules for applications

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• bonds, and 1,3-dipolar cycloaddition reactions to construct five-membered heterocycles are both powerful tools for assembling organic molecules. Used in combination, these tools offer great flexibility for strategies such as diversity-oriented synthesis [1], solution-phase combinatorial libraries [2

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• 10.3762/bjoc.7.175 Abstract An improved total synthesis of (−)-julocrotine in three steps from Cbz-glutamine, in 51% overall yield, is presented. To demonstrate the potential of the heterocyclic moiety for diversity oriented synthesis, a series of (−)-julocrotine analogues was synthesized by employing the

• heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1]. Keywords: diversity oriented synthesis; julocrotine; leishmania; Mitsunobu reaction; Ugi reaction; Introduction Julocrotine (1) is a natural glutarimide alkaloid isolated from several plants of the genus Croton [2][3][4

• , and melting point of 1 were consistent with the reported data [2][14][15]. For the diversity oriented synthesis the advanced intermediate 5 was used as the amino component in an Ugi-4CR with (S)-2-methylbutanoic acid, hydrophobic amino acids, formaldehyde and tert-butyl isocyanide (Scheme 2). These

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• are used as common intermediates for post-condensation modifications such as cycloaddition, Liebeskind–Srogl reaction and Suzuki coupling to form biaryl-substituted dihydropyrimidinone, dihydropyrimidine, and thiazolopyrimidine compounds. The high efficiency of the diversity-oriented synthesis is

• achieved by conducting a multicomponent reaction for improved atom economy, under microwave heating for fast reaction, and with fluorous solid-phase extractions (F-SPE) for ease of purification. Keywords: Biginelli reaction; dihydropyrimidine; diversity-oriented synthesis; fluorous; Suzuki coupling

• diversity-oriented synthesis of biaryl-substituted dihydropyrimidinone 5, thiazolopyrimidine 6, and dihydropyrimidine 7 compounds (Scheme 1). The perfluorooctanesulfonyl-attached benzaldehydes 1 were used as a key component for the Biginelli reactions [6]. The Biginelli products 4 were used as a common

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• ; multicomponent reactions; ynones; Introduction Diversity-oriented synthesis has become an important field in organic chemistry, initiated by the increasing demand for new scaffolds for pharmaceuticals and biologically active compounds over the past decades [1][2][3]. Herein, multicomponent reactions adopt a

• these intermediates into many classes of heterocycles [12][13][14][15]. These novel MCRs nicely correspond with diversity-oriented strategies towards functional organic chromophores [1][2]. The striking blue color of azulene (1a) (from the Spanish word “azul” = blue) has aroused scientific attention for

• , azulenes must be functionalized, either by halogenation or borylation, and some of these derivatives were found to be quite unstable [45][46]. To the best of our knowledge, no diversity-oriented multicomponent syntheses of azulenyl heterocycles have been reported so far. Here, we report the development of

The Eschenmoser coupling reaction under continuous-flow conditions

• Sukhdeep Singh,
• J. Michael Köhler,
• Andreas Schober and
• G. Alexander Groß

Beilstein J. Org. Chem. 2011, 7, 1164–1172, doi:10.3762/bjoc.7.135

• blocks as shown in Scheme 1. Due to the ease of accessibility of the building blocks and the usually high-yielding S-alkylation step, the Eschenmoser coupling is an interesting reaction for diversity-oriented combinatorial synthesis [15][16][17]. The new carbon–carbon bond formation occurs during the

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• membered cyclic imines. It allows the diversity-oriented synthesis of various tetrahydro[f][1,4]benzoxazepines. Keywords: benzoxazepines; cyclic imines; long range stereoinduction; multicomponent reactions; Ugi reaction; Introduction The Ugi reaction is probably the most renowned and widely used

• multicomponent reaction. Its great utility in the highly convergent and diversity-oriented synthesis of libraries of heterocyclic compounds, stemming from the possibility to introduce up to four diversity inputs in a single step, has been fully demonstrated [1][2][3][4][5]. However, a main drawback of this

C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

• Dhilli Rao Gorja,
• K. Shiva Kumar,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2011, 7, 338–345, doi:10.3762/bjoc.7.44

• cytotoxic activities in vitro. The methodology is amenable to the diversity-oriented synthesis of thieno[2,3-d]pyrimidine derivatives of potential pharmacological significance and therefore may find use in organic and medicinal chemistry. Diversity-based thieno[2,3-d]pyrimidine scaffold [7]. Possible

Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes

• Yannick Borguet,
• Xavier Sauvage,
• Guillermo Zaragoza,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133

• (Scheme 2). This process, known as assisted tandem catalysis [6], presents significant advantages over multistep synthesis for increasing molecular complexity, particularly in terms of time- and cost-savings, atom economy, environmental friendliness, or applicability to diversity-oriented high-throughput

Regioselective alkynylation followed by Suzuki coupling of 2,4-dichloroquinoline: Synthesis of 2-alkynyl- 4-arylquinolines

• Ellanki A. Reddy,
• Aminul Islam,
• K. Mukkanti,
• Venkanna Bandameedi,
• Dipal R. Bhowmik and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 32, doi:10.3762/bjoc.5.32

• water to afford 2-alkynyl-4-chloroquinoline. The arylation step is a Pd-mediated (Suzuki) coupling of 2-alkynyl-4-chloro derivative with arylboronic acids in aqueous media to give the target compounds. The process is amenable to the diversity-oriented synthesis of quinoline derivatives of potential

Zeolite catalyzed solvent- free one-pot synthesis of dihydropyrimidin- 2(1H)-ones – A practical synthesis of monastrol

• Mukund G. Kulkarni,
• Sanjay W. Chavhan,
• Mahadev P. Shinde,
• Dnyaneshwar D. Gaikwad,
• Ajit S. Borhade,
• Attrimuni P. Dhondge,
• Yunnus B. Shaikh,
• Vijay B. Ningdale,
• Mayur P. Desai and
• Deekshaputra R. Birhade

Beilstein J. Org. Chem. 2009, 5, No. 4, doi:10.3762/bjoc.5.4

• ) have recently gained tremendous importance in organic and medicinal chemistry. The main contributing factors are the high atom economy, wide application in combinatorial chemistry and diversity-oriented synthesis [4][5][6][7][8][9][10]. In general, the dihydropyrimidones (DHPMs) are known for their

Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium- catalyzed intramolecular C-H functionalization

• Florence Bonnaterre,
• Michèle Bois-Choussy and
• Jieping Zhu

Beilstein J. Org. Chem. 2008, 4, No. 10, doi:10.3762/bjoc.4.10

• heterocycles is evidently valuable in diversity oriented synthesis. The scope of this cyclization was next examined. From three aldehydes, eight amines, five carboxylic acids, and three isocyanides, Ugi-adducts were prepared and their subsequent palladium-catalyzed cyclization was investigated. The results are