Toward the total synthesis of maoecrystal V: an intramolecular Diels-Alder route to the maoecrystal V pentacyclic core with the appropriate relative stereochemistry

A diastereoselective route to the maoecrystal V core compound (6) has been achieved. Key transformations include an intramolecular Diels-Alder cyclization and an exo-glycal epoxide rearrangement sequence.     

Synthesis and RNA binding selectivity of oligonucleotides modified with five-atom thioacetamido nucleic acid backbone structures

Convenient chemical synthesis and incorporation of dithymidine and thymidine-cytidine dimer blocks connected with a five-atom amide linker N3'-CO-CH2-S-CH2 into oligonucleotides (ONs) are reported. The UV-Tm experiments for binding affinities of these mixed backbone ONs with complementary DNA and RNA sequences revealed important results such as significantly higher RNA-binding selectivity as compared with complementary DNA. NMR studies of the dimer blocks suggested a marginal increase in the N-type sugar conformations over that of the native DNA.     

Probing binding preferences of DNA and RNA: backbone chirality of thioacetamido-linked nucleic acids and iso-thioacetamido-linked nucleic acids to differentiate DNA versus RNA selective binding

Subtle differences in RNA and DNA duplex geometry could be sensed by the changed stereochemistry at 3'-amino function in the 5-atom thioacetamido linker of thioacetamido-linked nucleic acids and iso-thioacetamido-linked nucleic acids modified oligomers. In contrast to the preferred N-type sugar conformations for either 3'- ribo- or xylo amino nucleosides, predominant S-type sugar conformations were found in the dimers. Although the CD spectral differences for the dimer blocks were found to be identical for those found in phosphodiester linked ribo/xylo dimers, the 5-atom thioactamido linker could reverse the RNA binding selectivity to DNA binding selectivity by the change in configuration at the 3'-amino-substituted sugar.     

Unusually short RNA sequences: design of a 13-mer RNA that selectively binds and recognizes theophylline

RNA plays critical roles in numerous biological processes and constitutes valuable therapeutic targets. RNA is significant not only for its roles in transmitting the genetic code but also for its enzymatic functions in ribozymes and in peptide bond formation in ribosomes. Recent studies have shown that RNAs containing as few as 22 nucleotides can be key elements in cellular functions. This suggests the possibility of using short RNAs as regulatory elements. Here, we show that ligand recognition and selectivity by RNA molecules can occur with only the presence of a binding pocket and as few as six additional scaffolding nucleotides holding the binding pocket in place. A 13-mer RNA truncation of a 33-mer aptamer for theophylline preserves the ability to bind to theophylline and to discriminate against the structurally similar compound caffeine. The truncated aptamer retains nearly all of the same structural elements in its binding site as those present in the original aptamer. This is the first demonstration of selective ligand binding by a 13-mer RNA.     

Regiochemistry and stereochemistry of oxirane ring-opening with silyl halides

The ring-opening of various styrene and stilbene oxides with silyl halides was examined. The regiochemistry of ring-opening was independent of the silyl halide used, but the stereochemistry of ring-opening was sensitive to both the choice of halide and the steric bulk of groups attached to silicon.     

Silazane oligomers and polymers with phenylene spacing groups

Heating N,N′-diphenyltetramethylcyclodisilazane with phenylenediamines in the melt at temperatures over 200°C was found to yield oligomers composed of linear and cyclic disilazane units interlinked by phenylene groups. Increasing the temperature of the reaction of meta- and particularly para-phenylenediamine over 300°C promotes formation of crosslinked, infusible, and insoluble polymeric material. The succeeding steps of growth of the polymer molecules, which include cyclodisilazane ring cleavage, transaminations, and recyclizations, have been studied by elemental and spectroscopic analyses of the intermediate low molecular and oligomeric species in the distillable and nonvolatile products of the reactions.     

The stereochemistry of dichloroketene and chlorosulfonyl isocyanate cyclo-addition to 4-t-butylmethylenecyclohexane

The stereochemistry of the cycloaddition of dichloroketene (1) and chlorosulfonyl isocyanate (2) to 4-t-butylmethylenecyclohexane (4) has been investigated as a model for the 2π_s + 2π_a cycloaddition to the methylenecyclohexane system. The reactions are kinetically controlled and proceed mainly by axial attack to yield the thermodynamically less stable isomers 7 and 10, as major products, respectively.     

Effect of side chain and backbone length on lamellar spacing in polystyrene‐block‐poly(dimethyl siloxane) brush block copolymers

We report the synthesis of polystyrene‐block‐poly(dimethyl siloxane) (PS‐b‐PDMS) brush block copolymers (BBCPs) through sequential ROMP of norbornene‐modified macromonomers (‐NB) and explore the effect of side chain length (N_sc) and total backbone degree of polymerization (N_bb) on the self‐assembly of lamellar morphologies. Group I (PS‐NB M_n = 2.9 kg/mol, PDMS‐NB M_n = 4.8 kg/mol) exhibits asymmetric side chains, while Group II (PS‐NB M_n = 4.7 kg/mol, PDMS‐NB M_n = 4.8 kg/mol) possess a more symmetric arrangement. Both families rapidly self‐assemble into well‐ordered lamellar morphologies with domain spacings (d₀) ranging from d₀ = 54 to 140 nm. The scaling relationship between d₀ and N_bb (d₀ ~N_bb^α) was determined as the measure of backbone flexibility. Exponents of α = 0.71 and α = 0.81 are observed for Groups I and II, respectively, indicating the BBCPs adopt an extended backbone conformation. The presence of a low T_g side chain such as PDMS increases apparent flexibility of the backbone. The interplay between contrasting characteristics of the side chains is discussed and reveals the importance of understanding the physical consequences of block architecture on controlling BBCP assembly. These findings provide necessary information for future investigations of complex phases and well‐defined nanostructures fabricated using the brush architecture. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 691–699     

Synthesis and biochemical evaluation of des-vinyl secologanin aglycones with alternate stereochemistry

Based on the X-ray structure of the enzyme strictosidine synthase, the glucose moiety of the seco-iridoid glucoside, secologanin, appears to be the key for orienting the substrate. We hypothesized that removing the glucose moiety would allow alternate stereoisomers of secologanin to be turned over. A convenient synthesis to prepare stereoisomers of des-vinyl secologanin is presented. The choice of protective group was the key to access this series of compounds. The analogs were assayed with strictosidine synthase and, interestingly, both the natural 2,4-trans diastereomer and the unnatural 2,4-cis diastereomer are turned over. The trans/cis selectivity increases with increased acetal substituent size. The results add to our understanding of how strictosidine synthase discriminates among stereoisomers.     

Reactions of Thiocarbamoyl compounds with vaska complexes: mechanism and stereochemistry

Bis(dimethylthiocarbamoyl)sulfide, (Me₂NCS)₂S, reacts with (PH₃P)₂MCOCl complexes giving ionic species [Ph₃PM(η²-CSNMe₂)(S₂CNMe₂)CO]X (M = Rh, Ir; X = Cl, PF₆) as kinetic products. On standing solution, [Ph₃PRh(η²-CSNMe₂)(S₂CNMe₂)CO]Cl is slowly transformed into the thermodynamic product Ph₃PRh(η²-CSNMe₂)S₂CNMe₂)Cl. The known reactions of Vaska-type complexes with Me₂NCSCl to give [trans-(Ph₃P)₂Ir(η²-CSNMe₂)COCl]Cl and trans-(Ph₃P)₂Rh(η²-CSNMe₂)Cl₂ probably follow a similar course. (PH₃P)RuNOCl reacts with (Me₂NCS)₂S and Me₂NCSCl in the same way as (Ph₃P)₂IrCOCl, but reacts with (Me₂NCS)₂NPh to give [trans-(Ph₃P)₂Ru(η²-CSNMe₂)NOCl]PF₆. The mechanism and stereochemistry of these reactions are discussed. Reactions were monitored by NMR spectroscopy in an attempt to identify intermediate η¹-thiocarboxamido complexes, but no such species could be detected.     

Spin-label ESR with nanochannels to improve the study of backbone dynamics and structural conformations of polypeptides

Nanochannels of mesoporous silica materials were previously found useful for reducing the tumbling motion of encapsulated biomolecules while leaving the biomolecular structure undisturbed. Here we show that experiments of cw-ESR distance measurement in nano-confinement can benefit immediately from the above mentioned features of sufficiently slow molecular tumbling, enabling more accurate determination of interspin distances throughout the temperature range, from 200 to 300 K. A 26-residue prion protein peptide, which can fold into either a helical or hairpin structure, as well as its variants, are studied by using ESR. By comparing the spectra obtained in vitrified bulk solutions vs. mesopores, the spectra from the latter display typical slow-motional lineshapes, thereby enabling dipolar anisotropy to be unambiguously revealed throughout the temperature range, whereas the spectra from the former are dominated by the disordering of the side chain and the rotational tumbling of the peptide. The spectral changes regarding the two secondary structures in nano-confinement are found to show a strong correlation with the dynamic properties of the backbones. The effect of viscosity agent perturbation on the motion of an R1 nitroxide side chain, a commonly employed probe, could be substantial in a bulk solution condition, though it is absolutely absent in nanochannels. Under nano-confinement, the probe is proven sufficiently sensitive to the backbone motions. Overall, the distance distributions determined from the mesopore studies not only describe the conformational structures (by average distances), but also the backbone dynamics (by distribution widths) of the spin-labeled peptides.     

Synthesis of alkyl glycerolipids with various cationic groups linked directly to the glycerol backbone

A number of positively charged lipids containing pyridinium,N-methylmorpholinium,N-methylimidazolinium, 4-N,N-dimethylaminopyridinium, and 4-N,N-dimethylcyclo-hexylammonium groups linked directly to the C(3) atom of 1,2-di-O-alkylglycerols with Br⁻, MsO⁻, and TsO⁻ anions as counterions were synthesized. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1381–1384, July, 1999.     

Mechanism of benzylsuccinate synthase: stereochemistry of toluene addition to fumarate and maleate

Benzylsuccinate synthase catalyzes a highly unusual reaction: the addition of toluene to fumarate to form (R)-benzylsuccinic acid. The stereochemistry of this reaction has been examined using [d3-methyl]toluene and either fumarate or its cis stereoisomer, maleate, as the substrates. We demonstrate that when fumarate is the cosubstrate, deuterium is transferred from toluene to the C-3 pro-(R) position of benzylsuccinate, implying a syn addition of toluene to the double bond of fumarate. However, when maleate is the cosubstrate, the addition of toluene occurs in an anti fashion, so that deuterium transfer to the C-3 pro-(R) position of benzylsuccinate is also observed. This is consistent with the formation of the C-3 radical of benzylsuccinate as an intermediate, in which rotation about the C-2-C-3 bond can occur to relieve the sterically unfavorable cis conformation of the carboxylate groups when maleate is the cosubstrate.     

HUNTER: A conformational search program for acyclic to polycyclic molecules with special emphasis on stereochemistry

A new conformational search program, HUNTER, connected with the force fields MMP2 and MM3(92) is presented. The program accepts all types of molecules with most different substructures, considers stereochemical facts, and covers conformational space efficiently and completely. The most important facilities are an automated analysis of the stereochemistry including topographical facts, a separate perturbation of the acyclic and cyclic parts of the molecule using modified corner flapping, and an incremental rotation around single bonds with fixed flap and rotation angles, respectively; an exclusion of high energy structures by simulated annealing; the choice of the conformer lowest in energy, which is new as an initial structure for the next sampling run; and the use of a reduced set of dihedral angles to define a conformation. A specifically devised graphic interface, SERVANT, is used to feed in and control all informations necessary for a program run and to visualize the results. Most of the parameters are user-defined and thereby allow a flexible search, including a search for the most stable diastereomer. The efficiency of the different parameter sets was tested in calculation with cycloundecane ( 12 ), (Z)-oct-3-ene ( 13 ), and sipholenol-A monoacetate ( 14 ). The best performance regarding the number of different low-energy conformers was achieved with 60° ( 14 ) and 90° flaps ( 12 ), respectively, including substituent correction for the cyclic parts, and with 105° ( 14 ) and 120° rotations ( 13 ), respectively, for the acyclic parts. In comparison to the stochastic search routine implemented in MM3(92), HUNTER performed two ( 12 ) to six ( 14 ) times better. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1264–1281, 1997     

Synthesis and properties of a new AIE macrocyclic emitter with triarylamine backbone

A new macrocyclic AIE emitter composed of triarylamine backbone was successfully synthesized through convenient homocoupling procedure and easily purified by silica gel column chromatography, and recrystallization. The optical and electrochemical properties of the compound have been investigated. Intriguingly, the compound shows dual emission both 423 nm and 505 nm. This result implied that the violet emission was originated from an isolated component of the emitter, whereas the yellowish-green emission simultaneously exhibited AIE nature. The compound exhibits enough thermal stability and high glass transition temperature to be applied for organic devices.     

Synthesis and application of novel ionic phosphine ligands with a cobaltocenium backbone

Six novel ionic phosphine ligands with a cobaltocenium backbone, 1,1′-bis(dicyclohexylphosphino) cobaltocenium hexafluorophosphate () (1a), 1,1′-bis(di-iso-propylphosphino) cobaltocenium hexafluorophosphate () (2a), 1,1′-bis(di-tert-butylphosphino) cobaltocenium hexafluorophosphate () (3a), and the monophosphine ligand (Cc⁺ = cobaltocenium; R = Cy, 1b; R = i-Pr, 2b; R = t-Bu, 3b) were synthesized and characterized by elemental analysis, spectroscopy, and X-ray diffraction techniques. These ligands are air-stable and useful for Suzuki coupling reactions in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (), enabling high catalytic activity.