Organic & Biomolecular Chemistry (v.15, #34)

Front cover (7053-7054).

Contents list (7055-7062).

Amyloid scaffolds as alternative chlorosomes by Rolando F. Rengifo; Noel X. Li; Anthony Sementilli; David G. Lynn (7063-7071).
Living systems contain remarkable functional capability built within sophisticated self-organizing frameworks. Defining the assembly codes that coordinate these systems could greatly extend nanobiotechnology. To that end, we have highlighted the self-assembling architecture of the chlorosome antenna arrays and report the emulation and extension of their features for the development of cell-compatible photoredox materials. We specifically review work on amyloid peptide scaffolds able to (1) organize light-harvesting chromophores, (2) break peptide bilayer symmetry for directional energy and electron transfer, and (3) incorporate redox active metal ions at high density for energy storage.

A decade of DNA-hybrid catalysis: from innovation to comprehension by Nicolas Duchemin; Isabelle Heath-Apostolopoulos; Michael Smietana; Stellios Arseniyadis (7072-7087).
In a little over a decade, the unique chirality of oligonucleotides has allowed the development of a variety of asymmetric synthetic transformations. The concept lies in embedding an achiral transition metal catalyst in a DNA double helix, which provides the necessary chiral microenvironment to selectively form one enantiomer of a given reaction product. The most recent efforts at unveiling new reactivities have been accompanied by the desire to understand the mechanisms by which the chirality is transferred and the influence of the interaction between DNA and the metallic co-factor on the selectivity. By offering a complete overview of the field, this review aims to highlight the intricate correlation between the structure of the chiral bio-inorganic scaffold and its catalytic efficacy.

Rhodium(iii)-catalyzed and MeOH-involved regioselective mono-alkenylation of N-arylureas with acrylates by Honggui Lv; Jingjing Shi; Junjun Huang; Chao Zhang; Wei Yi (7088-7092).
We herein disclose, for the first time, Rh(iii)-catalyzed and MeOH-involved regioselective mono-alkenylation of arenes with acrylates using NHCONMe2 as the transformable directing group, giving direct access to diverse ortho-acrylated N-phenyl carbamates. The synthetic application of the obtained products to build privileged quinolin-2(1H)-ones and 3-(2-aminophenyl)acrylates has also been demonstrated in subsequent derivatization reactions.

A Pd(0)-catalyzed elimination of an allylic acetate generates a π-allyl complex that is postulated to initiate a novel intramolecular Diels–Alder cycloaddition to a tethered furan (IMDAF). Under the reaction conditions, this convergent, microwave-accelerated cascade process provides substituted indoles in moderate to good yields after Pd-hydride elimination, aromatization by dehydration, and in situ N-Boc cleavage.

Phosphine-catalyzed intramolecular Rauhut–Currier reaction: enantioselective synthesis of hydro-2H-indole derivatives by Hongxing Jin; Qinglong Zhang; Erqing Li; Penghao Jia; Ning Li; You Huang (7097-7101).
A highly enantioselective intramolecular Rauhut–Currier reaction catalyzed by a multifunctional chiral aminophosphine catalyst was reported. A series of hydro-2H-indole derivatives that bear an all-carbon quaternary center were obtained in high yields (up to 94%), and excellent diastereo- and enantioselectivities (up to >20 : 1 dr and >99% ee). And this reaction could be performed on a gram scale using 2 mol% catalyst loading.

7-Step total synthesis of (+)-EBC-329: Photoisomerisation reveals new seco-casbane family member by Timothy J. Vanden Berg; David M. Pinkerton; Craig M. Williams (7102-7105).
The first seco-casbane, EBC-329, isolated from the Australian rainforest, was synthesised from (+)-2-carene in seven steps. This endeavour not only established the absolute stereochemical assignment as (8R,9S)-EBC-329, but also identified, via photoisomerisation, a new seco-casbane family member.

syn-BN-heteroacene cored conjugated oligomers with finely tuned blue-violet luminescent properties by Wanzheng Zhang; Yubin Fu; Peirong Qiang; Jens Hunger; Shuai Bi; Wenbei Zhang; Fan Zhang (7106-7111).
Initiated by the effective dibromination of syn-BN-heteroacenes, a series of BN-containing conjugated oligomers was successfully synthesized upon transition-metal-catalyzed cross coupling. Their electronic structures can be finely tailored through varying the fused backbone or terminal substituents, endowing them with tunable luminescent properties within blue-violet regions.

An iodine-catalyzed multiple C–H bond functionalization of isoquinolines with methylarenes via a successive benzylic sp3 C–H iodination/N-benzylation/amidation/double sp2 C–H oxidation sequence is developed. This reaction utilizes un-functionalized isoquinolines and readily available methylarenes as starting materials, proceeds under metal-free conditions, and avoids a multi-step experimental operation, to make it an efficient and practical method for the synthesis of N-benzyl isoquinoline-1,3,4-triones.

PhenDV, a turn-off fluorescent quadruplex DNA probe for improving the sensitivity of drug screening assays by Claire Beauvineau; Corinne Guetta; Marie-Paule Teulade-Fichou; Florence Mahuteau-Betzer (7117-7121).
We report a new turn-off fluorescent probe, PhenDV, for the identification of high affinity quadruplex (G4) DNA ligands. This push–pull fluorophore displays a high fluorescence quantum yield in water (ΦF = 0.21) and is a selective and strong quadruplex DNA binder. We describe its use as a fluorescent indicator for the G4 Fluorescent Intercalator Displacement (FID) assay as its fluorescence is strongly quenched when bound to G4 DNA and fully restored when displaced by ligand. This probe improves the sensitivity of the G4-FID assay, as the read out relies on increased fluorescence instead of quenching observed with classical on/off probes.

Ratiometric electrochemical detection of β-galactosidase by Sam A. Spring; Sean Goggins; Christopher G. Frost (7122-7126).
A novel ferrocene-based substrate for the ratiometric electrochemical detection of β-galactosidase was designed and synthesised. It was demonstrated to be an excellent electrochemical substrate for β-Gal detection with sensitivity as low as 0.1 U mL−1.

Direct carboxamidation of cyclic 2-diazo-1,3-diketones by Rh2(OAc)4-catalyzed isocyanide insertion–hydrolysis by Xinwei He; Zhiyu Yu; Youpeng Zuo; Cheng Yang; Yongjia Shang (7127-7130).
A novel and efficient strategy for the synthesis of 2-hydroxy-6-oxocyclohex-1-enecarboxamides through a Rh2(OAc)4-catalyzed direct carboxamidation of cyclic 2-diazo-1,3-diketones has been developed. The method features readily available starting materials, easy scalability, mild reaction conditions and a simple work-up for product isolation, which makes this strategy highly attractive. A tentative mechanism involving an isocyanide insertion and hydrolysis sequence for this reaction is proposed.

Transition metal-catalyzed hydroalkenylation is widely applied in organic synthesis to construct carbon–carbon bonds and synthesize substituted alkenes. In this work, the mechanism and regioselectivities of [(NHC)NiH]+-catalyzed intramolecular cycloisomerization of dienes are studied by density functional theory (DFT) calculations. Through an initial hydride insertion, [(NHC)NiH]+ reacts with the diene substrate to generate the alkyl nickel species. This alkyl nickel species is the resting state of the catalytic cycle, and the hydroalkenylation reaction involves sequential olefin insertion and β-hydride transfer. The selectivity between the possible cycloisomerization products is determined by both the olefin insertion and β-hydride transfer steps. The olefin insertion favors the exo-cyclization due to the high ring strain of the insertion transition states for the endo-cyclization. In the β-hydride transfer step, the hydride transfers to the internal olefin position selectively to avoid the steric repulsions between the bulky NHC ligand and the alkyl substituent of the olefin substrate. This selectivity of β-hydride transfer leads to the n-exo cyclization instead of the (n− 1)-exo cyclization. These mechanistic insights will shed light on the future development of transition metal-catalyzed hydroalkenylation reactions.

Synthesis of Cu-catalysed quinazolinones using a Csp3–H functionalisation/cyclisation strategy by Aniket V. A. Gholap; Soham Maity; Carola Schulzke; Debabrata Maiti; Anant R. Kapdi (7140-7146).
A series of 2,3-disubstituted-4(3H)-quinazolinones were synthesised via a copper-catalysed Csp3–H functionalisation/cyclisation of 2-amino-N,N-dialkylbenzamides. In comparison to the reported methods this strategy allows an easy access to diversely substituted quinazolinones under mild conditions in air. The reaction also exhibits good functional group tolerance and would be of value to heterocyclic researchers as well as pharmaceutical process chemists. The reaction is proposed to proceed through a double SET type radical mechanism.

Dinuclear zinc complex catalyzed asymmetric methylation and alkynylation of aromatic aldehydes by Shanshan Liu; Gao-Wei Li; Xiao-Chao Yang; De-Yang Zhang; Min-Can Wang (7147-7156).
A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.

Application of α-amino acids for the transition-metal-free synthesis of pyrrolo[1,2-a]quinoxalines by Huanhuan Liu; Feiyu Zhou; Wen Luo; Yuxin Chen; Chenyang Zhang; Chen Ma (7157-7164).
A practical and concise protocol for the efficient synthesis of pyrrolo[1,2-a]quinoxalines from readily available α-amino acids and 2-(1H-pyrrol-1-yl)anilines under transition metal-free conditions has been established. This protocol, which includes the formation of new C–C and C–N bonds, features a wide substrate scope with a broad range of functional group tolerance.

pH-Responsive quencher-free molecular beacon systems containing 2′-deoxyuridine units labeled with fluorene derivatives by Ji Won Lee; Ye-Seul Son; Jun Yeon Hwang; Yoojin Park; Gil Tae Hwang (7165-7172).
Three fluorescent nucleosides—UFL, UAF, and UDAF, containing fluorene, 2-aminofluorene, and 2-dimethylaminofluorene units, respectively, covalently attached to 2′-deoxyuridine—have been incorporated into the central positions of oligodeoxynucleotides (ODNs) to examine the effects of their flanking bases (FBs) and pH on the emission properties upon hybridization with fully matched and single-base-mismatched targets. The ODN containing UFL and cytosine-FBs in the pH range from 5.5 to 8.0 and the ODN containing UDAF and cytosine-FBs under slightly acidic conditions (pH 6.0–6.5) exhibited dramatic increases in fluorescence only upon duplex formation with their fully matched target DNAs.

The first total synthesis and solution structure of a polypeptin, PE2, a cyclic lipopeptide with broad spectrum antibiotic activity by Simon J. Mountford; Biswaranjan Mohanty; Kade D. Roberts; Heidi H. Yu; Martin J. Scanlon; Roger L. Nation; Tony Velkov; Jian Li; Philp E. Thompson (7173-7180).
The first total synthesis of a polypeptin, PE2, as well as its solution structure is reported. Synthesis in optically pure form confirms the proposed stereochemistry of the polypeptins at the 3-position on the 3-hydroxy depsipeptide moiety. We have also determined the NMR structure of PE2 in aqueous solution, showing it to form a stable ring conformation. The synthetic peptide shows anti-bacterial activity consistent with reports for naturally derived counterparts.

Mild synthesis of triarylsulfonium salts with arynes by Lei Zhang; Xiaojin Li; Yan Sun; Weizhao Zhao; Fan Luo; Xin Huang; Lihui Lin; Ying Yang; Bo Peng (7181-7189).
Reactions between arynes and alkyl sulfides have been extensively studied over the past few decades. These reactions commonly end with a dealkylation process and thus deliver thioethers as final products. In contrast, the transformation described furnishes valuable triarylsulfonium salts, in lieu of thioethers, from arynes and diarylsulfides. The reaction features mild conditions and a broad substrate scope. A suite of functional groups such as ketones, esters, nitriles, aryl ethers and aryl halides is tolerated, which can be issues faced by traditional synthetic methods. The practicality of the reaction and its extension to the synthesis of triphenyl selenonium salt are also exhibited herein.

A mild two-step propargylation of aromatic bioactive small molecules by Naoki Kanoh; Toshitaka Okamura; Takahiro Suzuki; Yoshiharu Iwabuchi (7190-7195).
A two-step method for introducing a propargyl group in aromatic bioactive small molecules has been developed. This method features propargylation of aromatic groups using a cationic propargyl hexacarbonyl complex in the presence of cesium carbonate, and decomplexation of the resultant cobalt complexes using 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate. These reactions proceed under mild conditions, and thus are applicable for acid- and/or oxidant-sensitive aromatic bioactive small molecules.

Total syntheses of smenothiazoles A and B by Xiao Ma; Yajie Chen; Sigui Chen; Zhengshuang Xu; Tao Ye (7196-7203).
Concise total syntheses of smenothiazoles A (1) and B (2), two distinguished vinyl chloride containing natural products isolated from the marine sponge S. aurea, have been developed. Silastannation, Stille reaction and a carefully controlled desilylchlorination were employed as key steps to construct unique polyketide acid fragments, and the optimized reaction conditions avoided migration of 2,5-diene to a 2,4-conjugated system. This report unambiguously confirmed the structures of both natural products.

Palladium-catalyzed tandem cyclization/sulfonylation of homoallenyl amides with sodium sulfinates by Yimei Wan; Jian Zhang; Yongtao Chen; Lichun Kong; Fang Luo; Gangguo Zhu (7204-7211).
A palladium-catalyzed cyclizative sulfonylation of homoallenyl amides using sodium sulfinates as the sulfonylation reagent and PhI(O2CCF3)2 as the oxidant has been realized. The reaction proceeds at room temperature and produces structurally diverse 2-amino-5-sulfonylmethylfurans in good to excellent yields. A Pd(ii)/Pd(iv) catalytic cycle has been proposed for the formation of sulfonylated furans. The concurrent formation of a furan moiety and a C(sp3)–sulfur bond in a single operation makes it a very attractive method for organic synthesis.

2,4-Diamino-1,3,5-triazine-enabled Cu-catalyzed direct sulfonamidation of aromatic C–H bonds by Chan Song; Tao Wang; TingTing Yu; Dong-Mei Cui; Chen Zhang (7212-7217).
An efficient copper acetate catalyzed sulfonamidation of arenes via C–H bond activation directed by a 2,4-diamino-1,3,5-triazine chelating group under oxygen as a terminal oxidant has been developed. The reaction shows good regioselectivity and functional group tolerance, as well as providing a straightforward methodology for the preparation of ortho-monosulfonamidated arene derivatives in moderate to high yields. The sulfonamidation at the gram scale can be performed with a good yield.

Highly regio- and stereoselective trans-iodofluorination of ynamides enabling the synthesis of (E)-α-fluoro-β-iodoenamides by Yang Xi; Guohao Zhu; Luning Tang; Shihan Ma; Dongming Zhang; Rong Zhang; Guangke He; Hongjun Zhu (7218-7226).
A highly regio- and stereoselective trans-iodofluorination reaction of ynamides with NIS and Et3N·3HF has been achieved, affording (E)-α-fluoro-β-iodoenamides in moderate to good yields. The reaction proceeds under mild reaction conditions and exhibits good functional group compatibility.

Palladium-catalyzed allylic amination: a powerful tool for the enantioselective synthesis of acyclic nucleoside phosphonates by Mariam Azzouz; Sébastien Soriano; Margarita Escudero-Casao; M. Isabel Matheu; Sergio Castillón; Yolanda Díaz (7227-7234).
Acyclic nucleoside phosphonates have been prepared in a straightforward manner and in high yields by an enantioselective palladium-catalyzed allylic substitution involving nucleic bases as nucleophiles followed by cross-metathesis reaction with diethyl allylphosphonate.

Ring-closure of substituted 2-chlorosuccinates to α- or β-lactones has been studied by means of MP2/6-311+G(d,p)//MP2/6-31+G(d) calculations in water treated as a polarised continuum (PCM) and in vacuum. Optimised geometries have been obtained for 2-chlorosuccinate and its 2-methyl, 3,3-dimethyl, and 2,3,3-trimethyl derivatives, along with the transition structures and products for intramolecular nucleophilic displacement leading to the 3- or 4-membered rings. Relative enthalpies and Gibbs free energies of activation and reaction are presented, along with key geometrical parameters, and changes in electrostatic-potential-derived atomic charges. The difference in free-energy barriers for α- and β-lactone formation from the 2-methyl substrate at 298 K is less than 1 kJ mol−1. Primary 14C kinetic isotope effects calculated for substitution at C2 are significantly smaller for α-lactone formation than for β, suggesting a possible way to distinguish between the competing pathways of reaction. The B3LYP method without dispersion corrections predicts the wrong relative stability order for methyl-substituted succinate dianions in PCM water.

Back cover (7241-7242).