A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• ], but also allow access to diverse chemical structures [21] from readily accessible building blocks. In the past decades, considerable efforts have been made towards the development of new MCRs and their application to the diversity-oriented synthesis of biologically relevant molecules for drug

• Taofeng Shao Zhiming Gong Tianyi Su Wei Hao Chao Che Laboratory of Chemical Genomics, Engineering Laboratory for Chiral Drug Synthesis, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China 10.3762/bjoc.13.82 Abstract Diversity-oriented

• synthesis of the biologically intriguing imidazo[1,2-a]pyridine-fused isoquinoline systems from readily available starting materials was achieved through the Groebke–Blackburn–Bienaymé reaction followed by a gold-catalyzed cyclization strategy. The synthetic approach is characterized by mild reaction

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• accessibility of the starting materials, the mild reaction conditions, and the importance of products as B-ring-modified analogues of brazilin should make this synthetic work a useful addition in the diversity-oriented synthesis of natural-product like molecules. Moreover, since enantiomerically pure/enriched

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• most efficient tools in modern synthetic organic chemistry, since they have all features that contribute to an ideal synthesis: high atom efficiency, quick and simple implementation, time and energy saving, environment-friendly and they offer a target and diversity-oriented synthesis [20]. Therefore

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• demonstration of diversity-oriented synthesis, Chen and co-workers have shown that simply by switching the type of 6’-OH cinchona-derived catalyst used, two different products can be obtained in their reaction between the 2-cyclohexenone MBH derivative 90 and isatylidene malontirile 91, one of which is the [4

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• -225497. Keywords: cross metathesis; cyclic peptides; diversity oriented synthesis; macrocycle; Introduction Diversity-oriented synthesis (DOS) has been established as an important paradigm in drug discovery [1][2][3][4][5][6][7]. Although the major focus is on the synthesis of small molecular libraries

• [8], macrocyclic compounds are currently expanding the medicinal chemistry space [9][10]. Macrocyclic natural products [11] with significant levels of biological activity, and their analogues [12] are therefore receiving attention as targets for diversity-oriented synthesis. A class of cyclic tetra

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• otherwise difficult to synthesize following conventional retrosynthetic routes. This methodology can easily be extended for diversity-oriented synthesis [37] by employing different dienes and dienophiles during the DA reaction sequence. RRM route to propellane derivatives and oxa-bowls. Synthesis of the oxa

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• recurring motif in bioactive molecules. Consequently, assembling architecturally complex spirocycles is of great relevance to the diversity-oriented synthesis of biologically active spirocycles. In this context, new synthetic methods to generate multiple spirocenters in a simple manner remain a challenging

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• , this reaction has been used in the synthesis of bioactive peptides and pseudopeptides, e.g., tubulysin mimetics [13], julocrotine derivatives [14], architecturally complex peptoid macrocycles [15][16], building blocks for diversity-oriented synthesis [17], and heterocyclic compounds [18]. Complex

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -imidazo[1,2-b]pyrazole; isocyanide; multicomponent reaction; N-heterocycles; Introduction For the relatively rapid design and construction of a diverse, large pharmacophore library, the basic concepts of diversity-oriented synthesis and isocyanide-based multicomponent reactions, such as the Ugi four

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• synthetic stage, carbohydrate 4 is a versatile intermediate for the diversity-oriented synthesis of the related 2′-C-β-methyl-5′-deoxyribonucleosides. As the key intermediate for the preparation of the antitumor drug capecitabine [24][25], 5-deoxy-1,2,3-tri-O-acetyl-β-D-ribofuranose (6) is commercially

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• functions. An especially attractive approach is the use of already functionalized building blocks as starting materials in diversity oriented synthesis that increases the molecular complexity. Any synthetic methodology used in this context must take into account the sensitivity of the titanocene towards

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• -component reaction represents a rapid and excellent modular and diversity-oriented synthesis of donor-anthraquinone dyads with various phenothiazine and carbazole model donors. Cyclic voltammetry and UV–vis spectroscopy clearly indicate an electronic decoupling of the donor and the acceptor substituents in

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• conclusion, we enabled the diversity-oriented synthesis of novel triene merocyanines with intense bathochromic absorption by a consecutive three-component insertion–coupling–addition sequence in good to excellent yields. While the N-substituent on the indolone moiety exerts minute electronic differences in

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

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

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

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