Organic & Biomolecular Chemistry (v.12, #18)

Front cover (2813-2813).

Inside front cover (2814-2814).

Contents list (2815-2820).

Amplification by nucleic acid-templated reactions by Julia Michaelis; Alexander Roloff; Oliver Seitz (2821-2833).
Nucleic acid-templated reactions enable the design of conditional reaction systems, in which bond formation occurs only when a particular DNA or RNA molecule is present. Such reaction systems are currently being explored for applications in DNA/RNA diagnosis, drug screening and as a means to design gene expression specific therapy. However, biological nucleic acid templates usually have low abundance. Therefore, either the targeted nucleic acid template has to be multiplied by means of an amplification step or the template itself has to act as a catalyst which amplifies product formation. This critical review highlights the recent advancements in nucleic acid-templated reactions that proceed with turnover in template and thereby provide a means of amplification. Improvements in reaction engineering and the development of new chemistries have pushed the limits from 101 to 102–103 turnovers. This includes reaction systems that lead to the ligation of oligonucleotides or to the interconversion of appended functional groups beyond ligation as well as templated chemistries that enable the activation of catalysts for subsequent triggering of reactions between non-nucleotidic substrates. The present limitations and future opportunities are discussed.

Biopolymers have been used throughout history; however, in the last two centuries they have seen a decrease in their utilization as the proliferation of inexpensive and mass-produced materials from petrochemical feedstocks quickly became better-suited to meeting society's needs. In recent years, high petroleum prices and the concern of society to adopt greener and cleaner products has led to an increased interest in biorenewable polymers and the use of sustainable technologies to produce them. Industrial and academic researchers alike have targeted several routes for producing these renewable materials. In this perspective, we compare and contrast two distinct approaches to the economical realization of these materials. One mentality that has emerged we term “bioreplacement”, in which the fields of synthetic biology and catalysis collaborate to coax petrochemical monomers from sugars and lignocellulosic feedstocks that can subsequently be used in precisely the same ways to produce precisely the same polymers as we know today. For example, the metabolic engineering of bacteria is currently being explored as a viable route to common monomers such as butadiene, isoprene, styrene, acrylic acid, and sebacic acid, amongst others. Another motif that has recently gained traction may be referred to as the “bioadvantage” strategy, where the multifunctional “monomers” given to us by nature are combined in novel ways using novel chemistries to yield new polymers with new properties; for these materials to compete with their petroleum-based counterparts, they must add some advantage, for example less cost. For instance, acrylated epoxidized soybean oil readily undergoes polymerization to thermosets and recently, thermoplastic rubbers. Additionally, many plants produce pre-polymeric or polymeric materials that require little or no post modification to extract and make use of these compounds.

Triptycene-derived macrotricyclic polyether containing an anthracene unit is a powerful host for 1,2-bis(pyridium)ethane, diquat and 2,7-diazapyrenium salt with association constants of the 1 : 1 complexes at >105 M−1. Crystal structures showed that π–π stacking interactions between the host and the guests play an important role in the formation of the stable complexes.

An unexpected nucleophilic chlorination of a quinone monoketal while carrying out a pyrazolidine synthesis has led to a general preparation of multisubstituted phenols. The products are obtained in good to high yields under mild conditions. The bridged pyrazolidines that were the original targets are obtained in the presence of a protic solvent.

We demonstrated, for the first time, that on the basis of chemistry principles, the hexacyclic peptidyl alkaloid (−)-chaetominine (1) can be synthesized in a straightforward manner from l-Trp. The approach features the efficient generation of molecular complexity via a tandem C3/C14 syn-selective epoxidation (dr = 3 : 2)–annulative ring-opening reaction and a regioselective epimerization at C14. The successful production of (−)-chaetominine (1) from l-Trp could be helpful for revealing how the configuration of l-tryptophan becomes inverted in the biosynthetic pathway of (−)-chaetominine (1).

A Pd-based regioselective strategy to indole-1,2-fused 8- and 9-membered rings: their evaluation as potential scaffolds for apoptosis in zebrafish by Bagineni Prasad; B. Yogi Sreenivas; Araka Sushma; Swapna Yellanki; Raghavender Medisetti; Pushkar Kulkarni; Manojit Pal (2864-2868).
A strategy based on Pd-mediated ring closure of 1,2-disubstituted indoles containing an unactivated olefin leading to indole-1,2-fused 8- and 9-membered rings has been developed for the identification of new and potential scaffolds for apoptosis. A large number of fused indole derivatives containing an endocyclic double bond were synthesized using this robust methodology. A representative compound showed promising apoptotic properties in zebrafish embryos.

Gold-catalysed cyclisation of N-propargylic β-enaminones to form 3-methylene-1-pyrroline derivatives by Kommuru Goutham; N. S. V. M. Rao Mangina; Surisetti Suresh; Pallepogu Raghavaiah; Galla V. Karunakar (2869-2873).
A gold(i) catalysed reaction between N-propargylic β-enaminones and arynes was developed to access 3-methylene-1-pyrrolines. The title compounds were obtained in 57–78% yields. This reaction is useful for the generation of substituted 1-pyrrolines exhibiting significant molecular complexity.

Quadrupolar, emission-tunable π-expanded 1,4-dihydropyrrolo[3,2-b]pyrroles – synthesis and optical properties by Anita Janiga; Dominika Bednarska; Bjarne Thorsted; Jonathan Brewer; Daniel T. Gryko (2874-2881).
The synthesis and optical characterization of six novel heteroaromatic-based chromophores is described. The new dyes present mostly an A–D–A general framework, where A is an electron-deficient aromatic ring and D is an electron-rich pyrrolo[3,2-b]pyrrole moiety, linked via triple bonds. It was demonstrated that the increase in the molecular length of the chromophore effectively extends π-conjugation. The effect of structural variations on photophysical properties was studied in detail for these compounds and the relationship between the structure and photophysical properties was thoroughly elucidated by comparison with simpler tetraaryl-analogues. The strong charge-transfer characteristic of these functional dyes can be illustrated by large Stokes shifts (4100–7100 cm−1) for A–D–A architectures. The replacement of phenyl rings at positions 2 and 5 with the arylethynylaryl substituents bathochromically shifts both absorption and emission at ca. 50–150 nm. The clear dependence of fluorescence maxima on the electron-accepting property of the peripheral arylethynyl substituent emphasizes strong π-conjugation in these molecules. The donor–acceptor interactions were also found to influence the two-photon absorption properties.

Synthesis and biological activity of novel bis-indole inhibitors of bacterial transcription initiation complex formation by Marcin Mielczarek; Ruth V. Devakaram; Cong Ma; Xiao Yang; Hakan Kandemir; Bambang Purwono; David StC. Black; Renate Griffith; Peter J. Lewis; Naresh Kumar (2882-2894).
The increasing resistance of bacteria against clinically approved antibiotics is resulting in an alarming decrease in therapeutic options for today's clinicians. We have targeted the essential interaction between bacterial RNA polymerase and σ70A for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7′-, 2,2′-, 2,7′- and 3,2′-linked bis-indole derivatives with –CO–NH–NH–CO– and –CO–CO–NH–NH–CO– linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective –CO–CO–NH–NH–CO–CO– bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β′-CH-σ70/σA2.2 interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure–activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity.

Palladium-catalyzed air-based oxidative coupling of arylboronic acids with H-phosphine oxides leading to aryl phosphine oxides by Tingting Fu; Hongwei Qiao; Zhimin Peng; Gaobo Hu; Xueji Wu; Yuxing Gao; Yufen Zhao (2895-2902).
We present a novel and highly efficient methodology that allows for the construction of C–P bonds via the palladium-catalyzed air-based oxidative coupling of various commercially available arylboronic acids with easily oxidized H-phosphine oxides leading to valuable aryl phosphine oxides, particularly triarylphosphine oxides, with the use of air as the green oxidant, broad substrate applicability and good to excellent yields. The described catalytic system should be an efficient complement to the Chan–Lam type reaction and be useful in synthetic programs.

Copper-mediated trifluoromethylation of propargyl acetates leading to trifluoromethyl-allenes by Yun-Long Ji; Jun-Jie Kong; Jin-Hong Lin; Ji-Chang Xiao; Yu-Cheng Gu (2903-2906).
A copper-mediated trifluoromethylation of propargyl acetates with S-(trifluoromethyl)diphenylsulfonium triflate leading to trifluoromethylated allenes in moderate to excellent yields is described.

Five analogues of the macrocycle BPX26C6 are also capable of recognizing single urea and/or amide functionalities in the presence of templating Na+ ions. We have unambiguously confirmed the formation of such [2]pseudorotaxane complexes in solution through syntheses of the corresponding [2]rotaxanes.

A new approach towards the synthesis of pseudaminic acid analogues by Matthew Zunk; James Williams; James Carter; Milton J. Kiefel (2918-2925).
The pseudaminic acids are a family of 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids that are essential components of bacterial polysaccharides and glycoproteins. This paper describes our approach towards the synthesis of analogues of pseudaminic acid, and involves the efficient introduction of the requisite nitrogen functionalities from a readily available precursor.

A general strategy for the synthesis of phenylethanoid glycosides (PhG) including echinacoside 1, acteoside 2, calceolarioside-A 3 and calceolarioside-B 4 is reported. The strategy features the application of low substrate concentration glycosylation and N-formyl morpholine modulated glycosylation methods for the construction of 1,2-transβ- and α-glycosidic bonds. The reported strategy does not invoke the use of the participatory acyl protecting function, which is incompatible with the ester function present in target PhG compounds. A preliminary study of the anti-proliferation properties of the PhG compounds 1–4 was performed; the acteoside 2 exhibited the best inhibition on the prostatic cancer cell proliferation.

A computational study has been carried out in complexes formed by pyrrolidinium cation and aromatic units present in amino acid side chains. The interaction is stronger with indole (−21.9 kcal mol−1 at the CCSD(T) complete basis set level) than with phenol (−17.4 kcal mol−1) or benzene (−16.1 kcal mol−1). Most stable structures show a N–H⋯π contact between pyrrolidinium cation and the phenyl ring of the three aromatic species, except in phenol complexes where the most stable minimum shows a N–H⋯O hydrogen bond. In phenol and indole complexes, secondary contacts are established between the C–H groups of the carbon skeleton of pyrrolidinium and the aromatic rings or hydroxyl oxygen, being the main reason for the enhanced stability with respect to benzene, where these contacts are not possible. The interaction is mainly controlled by electrostatics, but contributions from induction and dispersion are also significant, especially the latter in indole complexes. These three attractive contributions increase their intensity when going from benzene to phenol and indole. Microhydration effects have been estimated by including up to three water molecules in the complexes. In monohydrated pyrrolidinium⋯benzene complex the most stable structure shows the water molecule coordinated to the cation without interacting with the ring. In phenol and indole, otherwise, the water molecule interacts with both the cation and the aromatic species, forming a cyclic hydrogen bond pattern π(phenyl)⋯H–N–H⋯O–H⋯X (X = π, O). This pattern is also present among the most stable structures found for complexes with two and three water molecules, though a variety of almost isoenergetic minima showing different hydrogen bond patterns have been found. Water molecules remove the stability differences between phenol and indole complexes, which already with two water molecules show similar stabilities, though around 5 kcal mol−1 larger than benzene ones.

A flexible stereoselective approach to the common C1–C14 skeleton present in natural products of the pseudomonic acid family is described. The strategy has been extended and the total synthesis of pseudomonic acid methyl monate C was achieved. The key synthetic reactions utilized include Achmatowicz rearrangement, Johnson–Claisen rearrangement, Julia–Kocienski olefination, and Horner–Wadsworth–Emmons olefination reaction.

Tailoring fluorescent strigolactones for in vivo investigations: a computational and experimental study by Cristina Prandi; Giovanni Ghigo; Ernesto G. Occhiato; Dina Scarpi; Stefano Begliomini; Beatrice Lace; Gabriele Alberto; Emma Artuso; Marco Blangetti (2960-2968).
Strigolactones (SLs) are a new class of plant hormones whose role has been recently defined in shoot branching, root development and architecture, and nodulation. They are also active in the rhizosphere as signalling molecules in the communication between plants, AMF (arbuscular mycorrhizal fungi) and parasitic weeds. In spite of the crucial and multifaceted biological role of SLs, the current knowledge on the SL biosynthetic pathway and the perception/transduction mechanism is still incomplete. Both genetic and molecular approaches are required to understand the molecular mechanism by which SLs regulate plant development. Our contribution to this topic is the design and synthesis of fluorescent labelled SL analogues to be used as probes for the detection in vivo of the receptor(s). Knowledge of the putative receptor structure will boost the research on analogues of the natural substrates as required for agricultural applications.

A novel KOAc-promoted α-position C–H activation and alkynylation of ethers with alkynyl bromides to 2-alkynyl ethers has been developed under transition-metal-free and simple reaction conditions. In addition, this methodology can also be extended to the vinylation of ethers with vinyl bromides in excellent regio- and stereo-selectivity. A wide range of direct C(sp)–C(sp3) and C(sp2)–C(sp3) bonds has been formed through this protocol, which offers a new and alternative route.

Back cover (2979-2980).