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

• an important class of organophosphorus compounds that has attracted the attention of both industrial and medicinal chemists [5][6][7][8][9][10][11][12]. Many efforts have been made to prepare these bioactive compounds over the last 60 years [13]. There are two general approaches to the synthesis of

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• offers the opportunity to find novel bioactive compounds with the potential to become drug leads. Regarding halotolerant myxobacteria, the 9 Mb genome of the Myxococcus fulvus strain HW-1 (ATCC BAA-855, suborder Cystobacterineae) was the first-of-its-kind to be sequenced [38]. Genome mining performed in

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• cellulolytic Sorangium strains harbor well-conserved homologs of both genes. Antibiotics from myxobacteria with a possible role in predation The following listing highlights few selected antibiotics from myxobacteria in the context of predation. For a comprehensive overview of bioactive compounds from

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• isolated from two solitary wasp species (Sceliphron caementarium and Chalybion californicum, Hymenoptera, Sphecidae) [100]. Based on a pre-screening of bacterial extracts, the detailed chemical analysis of selected strains revealed not only a broad range of known bioactive compounds, such as bafilomycins

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• applications ranging from advanced materials to bioactive compounds [1][2][3]. One such fluorinated functional group which has become the focus of systematic investigation only recently is the pentafluorosulfanyl (SF5) group [4][5]. The combination of high stability [6], lipophilicity [7] and strong electron

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• ; Findings Direct aminooxygenation of alkenes provides a straightforward and powerful approach to construct the 1,2-aminoalcohol skeleton [1], which is ubiquitous in bioactive compounds (such as the drugs bestatin (1) and tamiflu (2), the natural products Al-77-B (3) and hapolosin (4); Figure 1) [2] and has

• the cleavage of the N–O or C–N bond of the NHPI moiety. Further studies are underway in our lab. Bioactive compounds containing 1,2-aminoalcohol motif. The copper-catalyzed three-component aminooxygenation of styrenes with NFSI and NHPI derivatives. Reaction conditions: 1 (0.9 mmol, 3.0 equiv), NFSI

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• hormones were among the first bioactive compounds whose aqueous solubilities were shown to be significantly enhanced via CD inclusion. For example, in an early study by Uekama et al. [14], the interactions between 18 steroid hormones and the native cyclodextrins α-, β- and γ-CD in aqueous solution were

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• of such a catalytic strategy to access the target compounds 1–4 in an efficient manner. The availability of efficient catalytic processes is a fundamental requirement for the development of scalable synthetic routes of bioactive compounds. Thus, in the present work, we firstly reconsidered this

• to obtain both the enantiomers of chiral bioactive compounds. In this case, we focused on (R,R)-8a, which afforded the required (S)-7 (the absolute configuration has been previously determined by vibrational circular dichroism) [31]. Asymmetric synthesis of 9 by decarboxylation of (S)-7 Although

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• structural motifs for a broad range of compounds with applications as advanced fluorescent materials [2][3], ligands [4][5], bioactive compounds [6], and for the design of dynamic chemical devices [7][8][9][10]. The most accessible route to hybrid heteroarenes is the direct coupling [1][11][12]. However, in

• indolizines and azaindolizines are known as fluorescent materials [2][3][4][15] with applications as chemosensors [16] and as bioactive compounds [17][18][19][20]. For example, starting from bispyridyl derivatives such as 1 and 3, fluorescent compounds from the class of indolizines, as for example compounds 2

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• impossible to achieve [4][8][9]. The importance of cyclopentenones as intermediates to the synthesis of bioactive compounds prompted us to explore the synthetic potential of this novel rearrangement of 1-styrylpropargyl alcohols (Table 1). Toward this purpose, a number of other substrates were synthesized

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• substitution of the α-carbon to the cyano group. Keywords: design of experiment (DOE); 1,4-dithiane-2,5-diol; Gewald reaction; thiazole; thiophene; Introduction Thiazoles are privileged motifs which are encountered in many naturally occurring bioactive compounds and pharmaceuticals with indications in a

Ruthenium-catalyzed C–H activation of thioxanthones

• Danny Wagner and
• Stefan Bräse

Beilstein J. Org. Chem. 2015, 11, 431–436, doi:10.3762/bjoc.11.49

• . Keywords: C–H activation; metal catalysis; thioxanthones; Introduction Thioxanthones (Figure 1) belong as a unique member to the large group of benzoannelated heterocycles [1]. They have found extensive use in biomedical applications (drugs and other bioactive compounds [2][3][4][5]) and material sciences

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• trifluoromethylated derivatives play a major role in chemistry [28], their more lipophilic analogues – C2F5 [1][29][30] and SF5 [1][31] – only gain popularity. The C2F5-substituted derivatives, for example, often have higher activity compared with the CF3-counterparts [32][33]. Therefore, some bioactive compounds

• alkynes 1–12 with C2F5CHN2 gives 3,5-disubstituted ones. Also, alkaline hydrolysis of the ester group in 1a gave acid 25 – potential building blocks for medicinal chemistry and drug discovery: many bioactive compounds, including the insecticidal agent DP-23, contain the residue of the CF3-analogue of 25

• layer was separated. The aqueous layer was washed with CH2Cl2 (2 × 3 mL). The combined organic layers were dried over Na2SO4 and evaporated under vacuum to provide the pure product. Bioactive compounds and agrochemicals with fluorinated pyrazoles. Bioactive compounds with C2F5 group [34][35][36]. X-ray

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• bioactive compounds. For instance, thiadiazole containing heterocycles are known to exhibit important anti-inflammatory, antihypertensive, anti-HIV and antituberculosis activity [1]. Within this family, 1,2,4-thiadiazoles display notable medicinal properties as potent neuroprotectors [2

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• of a variety of polycyclic structures containing typical structural elements of bioactive compounds [82]. Since 73 provides manifold possibilities for structural modifications, the generation of complex and structurally diverse scaffolds could be achieved in very few steps (diversity-oriented

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• the corresponding biologically active compounds. These were used as raw mixtures (e.g., extracts for food supplements), as well as purified bioactive compounds for the treatment of various diseases. They were used in natural form or after derivatization to a more bioactive compound, such as the

• compounds. One of the most frequently used matrices for molecular encapsulation, protection against oxidation or other degradation processes, as well as controlled release of relatively small bioactive compounds, are cyclodextrins (CDs) [30][31][32][33][34][35]. These are cyclic oligosaccharides consisting

• small hydrophobic molecules and allow for an increased apparent aqueous solubility of nanoencapsulated bioactive compounds. Moreover, the access of oxygen or other oxidative agents to these bioactive compounds can be reduced. Essential oil components are some of the most appropriate molecules for

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• pharmaceutical compounds [1][2][3][4][5]. In particular, tetracyclic compounds containing the indole substructure represent an important structural motif in a variety of bioactive compounds, such as antitumor agents A [6] and antifungal agents B [7] (Figure 1). Therefore, it is necessary to develop efficient and

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• synthesis of bioactive compounds and natural products. At the end of the century, Lu and co-workers discovered the nucleophilic phosphine-catalyzed [3 + 2] annulation of allenes with electron-deficient imines and established a reasonable reaction mechanism [58][59][60]. Its asymmetric version, however, did

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

• bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be

• products and bioactive compounds discussed in this review. Phosphonamides by Arbuzov reaction An example for the application of the Arbuzov reaction is the synthesis of phosphonamide (R,R)-28a. Thus, heating of (R,R)-N,N’-dimethyl-1,2-diaminocyclohexane (58) with hexamethylphosphorus triamide gave the

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) . Keywords: aminohalogenation; diamination; α,β-diamino ester; one-pot; stereoselectivity; Introduction α,β-Diamino acid derivatives are one of the most important classes of nitrogen-containing bioactive compounds [1][2

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• complex products and bioactive compounds. Among the glycosans, the anhydro sugars involving the anomeric center in the ring formation, the 1,6-anhydro sugars are the most common and useful building blocks [1][2]. They can play a role in synthetic methodologies aiming at the obtainment of regioselectively

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• find use in the synthesis of natural products and other bioactive compounds. Experimental General procedure 1: Mitsunobu reaction with 4-hydroxy-2-pyrones: To a stirred solution of the pyrone (1 equiv), triphenylphosphine (1.5 equiv) and alcohol (1.5 equiv), in dichloromethane (4 mL mmol−1) under

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• acetates with azodicarboxylates in the presence of PPh3 (Mitsunobu reaction conditions), which gives an efficient access to α-alkylidene-β-hydrazino acid derivatives, an important precursor for many bioactive compounds [25][26][27][28][29][30] including β-amino acids [25] (Scheme 1, top). However, the

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• as a powerful tool for the synthesis of medium-sized libraries of bioactive compounds. Thus, straightforward syntheses of 1,3-disubstituted-1,2-dihydroisoquinolines have been achieved by three-component reactions between alkynylbenzaldehydes 25 (γ-carbonylalkyne), primary amines 26 (mainly anilines

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• Abstract A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis

• other bioactive compounds [1][2][3][4][5][6][7]. Selected examples are given in Figure 1: The non-peptidic human neurokinin-1 (NK1) substance P receptor antagonists L-733,060 [15][16] and CP-99,994 [17][18][19], the natural product febrifugine (antimalarial) [20][21] and antiprotozoal agent halofuginone