The reaction of acetic acid 2‐selenoxo‐2H‐pyridin‐1‐yl esters with benzynes: A convenient route to Benzo[b]seleno[2,3‐b]pyridines

Benzyne and its 3,4,5,6‐tetraphenyl, 3‐ and 4‐methyl, 3‐methoxy and 4,5‐difluoro derivatives react with acetic acid 2‐selenoxo‐2H‐pyridin‐1‐yl esters 4a‐e to give benzo[b]seleno[2,3‐b]pyridines 10–15 in modest yields. The benzynes were generated by one or more of the following methods: diazotization of anthranilic acids 5a‐g with isoamyl nitrate; mild thermal decomposition of 2‐diazoniobenzenecarboxylate hydrochlorides 6a‐d treatment of (phenyl)[o‐(trimethylsilyl)phenyl]iodonium triflate (7) with tetrabutylammonium fluoride; and treatment of 2‐trimethylsilylphenyl triflates 8a‐c with cesium fluoride. In all the reactions, the corresponding 2‐(methylselenenyl)pyridines 16a‐d were also obtained suggesting that these reactions may involve selenium addition to benzyne via a SET (single electron transfer).     

Total Synthesis and Biological Evaluation of Grassypeptolide A

Herein, we describe in full our investigations into the synthesis of grassypeptolide A ( 1 ) in 17 linear steps with an overall yield of 11.3 %. In particular, this work features the late‐stage introduction of sensitive bis(thiazoline) heterocycles and 31‐membered macrocyclization conducted at the sterically congested secondary amide site in superb conversion (72 % yield). Biological evaluation indicated that grassypeptolide A significantly inhibited cancer cell proliferation in a dose‐dependent manner. It induced cancer cell apoptosis, which was associated with increased cleavage of poly(ADP‐ribose) polymerase (PARP) and decreased expression of bcl‐2 and bcl‐xL. Furthermore, grassypeptolide A also caused cell cycle redistribution by increasing cells in the G1 phase and decreasing cells in the S and G2 phases. In addition, cell cycle arrest was correlated with downregulation of cyclin D and upregulation of p27 and p21.     

Synthesis and NMR elucidation of pentacycloundecane-derived hydroxy acid peptides as potential anti-HIV-1 agents

The synthesis and NMR elucidation of eight novel peptides incorporating the pentacycloundecane (PCU)-derived hydroxy acid are reported. The PCU cage amino acids were synthesized as racemates and the incorporation of the PCU-derived hydroxy acid with natural (S)-amino acids produced inseparable diastereomeric peptides. A series of overlapping signals from the cage and that of the peptide side chain was observed in the ¹H- and ¹³C-NMR spectra, complicating the elucidation thereof. Two-dimensional NMR techniques proved to be a very useful tool in overcoming these difficulties. These compounds are potential HIV protease inhibitors.     

Unraveling the concerted catalytic mechanism of the human immunodeficiency virus type 1 (HIV-1) protease: a hybrid QM/MM study

Structural Chemistry - We give an account of a one-step concerted catalytic mechanism of HIV-1 protease (PR) hydrolysis of its natural substrate using a hybrid QM/MM method. The mechanism is a...     

Experimental and theoretical studies on group 1 metallacarboranes: Synthesis, structure and ab initio calculations of the NMR chemical shifts of the 1-(THF)-1-(TMEDA)-1-Na-2,4-(SiMe3)2-2,4-C2B4H5 and related carboranes

The reaction of gaseous HCl with either the disodium or dilithium compound of the [nido-2,4-(SiMe₃)₂-2,4-C₂B₄H₄]²⁻ dianion (I) in 1:1 stoichiometry in THF produced the monoprotonated species 1-Na(THF)₂-2,4-(SiMe₃)₂-2,4-C₂B₄H₅ (II) or 1-Li(THF)₂-2,4-(SiMe₃)₂-2,4-C₂B₄H₅ (III), in 81% and 80% yields, respectively. This method proved superior to that involving the direct reduction of the closo-C₂B₄ carborane by metal hydrides. II and III were characterized by elemental analysis, ¹H, ¹¹B and ¹³C NMR and IR spectra. Compound II was recrystallized from a mixture THF, hexane and TMEDA (1:2:1) to isolate colorless crystals of the mixed solvated species, 1-(THF)-1-(TMEDA)-1-Na-2,4-(SiMe₃)₂-2,4-C₂B₄H₅ (IV), which were subsequently used for X-ray diffraction studies. The structure of IV showed that the capping metal occupied the apical position above the open C₂B₃ face of the carborane and that a hydrogen atom was bridging the two adjacent boron atoms on that face. The ¹¹B and ¹³C NMR spectra calculated by GIAO (gauge independent atomic orbital) methods at the 6-311G^** level on the B3LYP/6-31G^* optimized geometries of I–III, and a number of related nido- and closo-carboranes, gave excellent agreement with experiment, even in compounds where electron correlation effects are known to be important.     

Synthesis and stereoselective oxidation of α-thio-β-chloropropenyloxazolidin-2-ones

The investigation of the stereoselective reaction of α-thiopropanoyloxazolidin-2-ones with NCS to yield α-thio-β-chloropropenyloxazolidin-2-ones is described. Diastereoselective sulfur oxidation of the resulting α-thio-β-chloropropenyloxazolidin-2-ones shows modest diastereocontrol. However, via a combination of diastereoselective oxidation and subsequent kinetic resolution in the sulfoxide oxidation, diastereoselectivities of up to 94% de have been achieved.     

Laser collimation of an Fe atomic beam on a leaky transition

We report results of the first laser collimation of a thermal beam of Fe atoms on the leaky ⁵D₄ ⁵F₅ transition, with both parallel linear ^xx and crossed linear ^xy laser polarization configurations. The measured atomic beam divergence is compared to a rate-equation model and a quantum Monte Carlo model. The experimental values for the divergence are limited by the finite laser line width, which is comparable to the natural line width of the Fe atom. In general, flux decreases with higher intensities, showing the effect of the leaky transition. At the best beam collimation _RMS = 0.17 mrad, which is for a detuning of = – and a saturation parameter of s = 6, the flux decreased to approximately 70%. Highest flux was measured for a detuning of = –2 and s = 4, reaching 135% of the uncooled value. From our measurements we estimate the total leak rate to be 1/(240 ± 40), which is in good agreement with the literature value of 1/244. The crossed linear polarization configuration is the better choice, with a slightly better collimation but the same atomic beam flux. Plugging of the largest leak would increase the flux to at least 80% of the closed transition value, resulting in better contrast for atom lithography.     

Iron complex-catalyzed ammonia-borane dehydrogenation. A potential route toward B-N-containing polymer motifs using earth-abundant metal catalysts

Ammonia-borane (NH(3)BH(3), AB) has garnered interest as a hydrogen storage material due to its high weight percent hydrogen content and ease of H(2) release relative to metal hydrides. As a consequence of dehydrogenation, B-N-containing oligomeric/polymeric materials are formed. The ability to control this process and dictate the identity of the generated polymer opens up the possibility of the targeted synthesis of new materials. While precious metals have been used in this regard, the ability to construct such materials using earth-abundant metals such as Fe presents a more economical approach. Four Fe complexes containing amido and phosphine supporting ligands were synthesized, and their reactivity with AB was examined. Three-coordinate Fe(PCy(3))[N(SiMe(3))(2)](2) (1) and four-coordinate Fe(DEPE)[N(SiMe(3))(2)](2) (2) yield a mixture of (NH(2)BH(2))(n) and (NHBH)(n) products with up to 1.7 equiv of H(2) released per AB but cannot be recycled (DEPE = 1,2-bis(diethylphosphino)ethane). In contrast, Fe supported by a bidentate P-N ligand (4) can be used in a second cycle to afford a similar product mixture. Intriguingly, the symmetric analogue of 4 (Fe(N-N)(P-P), 3), only generates (NH(2)BH(2))(n) and does so in minutes at room temperature. This marked difference in reactivity may be the result of the chemistry of Fe(II) vs Fe(0).