Total syntheses of the tetracyclic terpene waihoensene and the densely functionalized tetracyclic compound ryanodol have recently been reported. Both approaches constitute examples of the efficient ...and innovative construction of multiple quaternary centers.
In high entropy alloys (HEAs), the formation of solid solution phase is governed by main factors such as mixing entropy, mixing enthalpy, atomic radii, and atomic size difference. However, factors ...such as electronegativity, valence electron concentration, and melting point, also significantly influence the formation of the solid solution phase, individually or in combination in specific alloys, and are often less studied and reported. In this work, CoCrFeNiX0.4 (X = Al, Nb, Ta, elements with equi-atomic radii) high entropy alloys have been prepared by powder plasma arc additive manufacturing (PPA-AM). The effect of equi-atomic radii element addition on the microstructural evolution was studied. The results showed that although Al, Nb, and Ta were equi-atomic radii element additions, the resulting HEAs had variations in their phase formation and mechanical properties. Following observations were made: (i) Al addition: FCC + BCC +Sigma phase formation with lowest hardness and (ii) Nb and Ta addition: FCC + Laves phase + Eutectic phases formation with relatively high hardness (>85%–～110% increase). Considering other factors that determine the formation of solid solution phase, it has been identified that: (i) high melting point of the metal has a superior influence on the formation of topologically closed packed phases (TCP) solid solution phase and (ii) elements with large electronegativity differences tends to be rich in the second solid solution phase. The HEAs deposited by PPA-AM have similar/better mechanical stability when compared to the as-cast alloys. Using an innovative AM technology to fabricate HEAs, this work emphasizes the importance of the control of multiple variables in manipulating the solid solution phase formation and mechanical properties of HEAs.
•CoCrFeNiX (X = Al, Nb, Ta) high entropy alloys fabricated by powder plasma arc additive manufacturing (AM).•Solid solution (SS) phase formation not governed only by equi-atomic radii of elements.•High melting point of elements influences topologically closed packed SS phase formation.•Large electronegativity difference in elements promotes SS phase formation.•AM fabricated alloys have better/similar microhardness than as-cast alloys.
Several monocyclic derivatives of 14,14′-difluororipostatin A were prepared using a catalytic Mukaiyama aldol reaction, a ring-closing metathesis reaction and a late stage click reaction as key ...steps. The biological activity of the produced compounds was assessed
in vivo
using a panel of pathogenic microorganisms. Moderate antibiotic activity was observed for 11-OMe-ripostatin A and 11-OMe-14,14′-difluororipostatin A.
A last stage click-chemistry approach to synthesize the heterocycle-containing derivatives of fluorinated ripostatin A was developed.
Efficient control of the infectious diseases in the era of the emerging bacterial resistance demands consistent development of new antibiotic agents with novel modes of action. With some notable ...exceptions, the majority of the currently used antibiotics are natural product-derived compounds which were elaborated upon lead structures discovered by screening of various isolates. In this review, we summarized some selected examples of recent advances in the area of natural product based antibiotic development with particular emphasis on the synthetic and SAR-elucidation aspects.
Keep me skipped: A highly convergent total synthesis of ripostatin B, an inhibitor of the bacterial RNA polymerase, is described. The key steps to construct and avoid isomerization of the skipped ...triene are a double Stille cross‐coupling reaction and a ring‐closing metathesis. Furthermore, 15‐deoxyripostatin A, a stable and conformationally locked analogue of ripostatin A (see scheme, 15‐OH group red), was prepared and tested in vivo.
•PPA-AM was employed to manufactured CoCrFeNi(SiC)x HEAs for the first time.•The effect of SiC content on CoCrFeNi matrix was studied for the first time.•With SiC added, the structure changed from ...FCC phase to FCC + Cr7C3 dual-phase.•With SiC added, the hardness and yield strength of HEAs were significantly improved.
In this study, powder plasma arc additive manufacturing (PPA-AM), a promising manufacturing technique was used for the first time to fabricate CoCrFeNi(SiC)x (x = 0, 0.1, 0.3 and 0.5) HEAs. Microstructure and mechanical properties of CoCrFeNi(SiC)x were investigated. With increasing of SiC content, the microstructure of CoCrFeNi(SiC)x HEAs changed from single FCC phase to FCC + Cr7C3 dual-phase, the hardness (from ~139 HV to ~310 HV) and yield strength (from ~142 MPa to ~713 MPa) were significantly improved. The strengthening mechanism of the HEAs is solid-solution and second phase strengthening.
Total Synthesis of Ripostatin A Tang, Wufeng; Prusov, Evgeny V
Organic letters,
09/2012, Letnik:
14, Številka:
17
Journal Article
Recenzirano
The first total synthesis of the bacterial RNA-polymerase inhibitor ripostatin A (1) was achieved. The route utilizes a cyclic methyl acetal intermediate and a sequence of a double Stille ...cross-coupling reaction followed by a ring-closing metathesis for the construction of the macrolactone ring. Additionally, an unprecedented formation of the 4-methoxy substituted tetrahydropyrans was observed during the acid catalyzed acetalization of the β,δ-dihydroxyketone.
Wooden multi-span beams with steel reinforcement were studied experimentally on a stationary stand using an eight-point loading scheme that simulated a load uniformly distributed over the beam span. ...The studies were carried out on beams with a span of 4.8 m with a cross-sectional area of 40 mm × 80 mm, reinforced in the stretched zones of the cross-section with rods made of hot-rolled steel reinforcement of A400 class. The rational zones for the location of reinforcements in the tensioned and compressed zones of the beams were determined. The rational placements of reinforcement in the support and span zones was based on the numerical simulation of the volumetric stress state calculated using the finite element method. It was experimentally confirmed that the failure of wood composite beams had a plastic nature and occurred only along normal sections. This excluded the possibility of brittle fracture from shear stresses and ensured the operational reliability of structures as a whole. It was shown that the proposed rational reinforcement of wooden beams increased their bearing capacity by 175% and reduced bearing deformability by 85%. The results obtained indicated high efficiency of the application of the developed method of reinforcement in beams of roofs and floors of buildings.
In high entropy alloys (HEAs), the addition of large-size atoms results in lattice distortion and further leads to solid solution strengthening or precipitation strengthening. However, the ...relationship between atomic radius, solid solution strengthening and precipitation strengthening has not been discerned yet. In this work, CoCrFeNiX0.4 (X = Al, Nb, Ta, with an equi-atomic radius) HEAs were prepared by powder plasma arc additive manufacturing (PPA-AM) and evaluated for their mechanical properties. Compression and nano-indentation hardness tests showed that the HEA with Ta showed the best properties. The influence of atomic radius and solid solubility on solid solution strengthening was investigated and the main strengthening mechanism that determines the mechanical properties of the developed HEAs was analyzed. The results showed that (i) the CoCrFeNiAl0.4 alloy did not show any solid solution strengthening effect and that a clear relation between solid solution strengthening and atomic size was not observed; (ii) in both CoCrFeNiTa0.4 and CoCrFeNiNb0.4 HEAs, precipitation strengthening and grain boundary strengthening effects are observed, wherein the difference in mechanical properties between both the alloys can be mainly attributed to the formation of fine eutectic structure in CoCrFeNiTa0.4; and (iii) from the microstructural analyses, it was identified that, in the CoCrFeNiTa0.4 HEA, the location containing a fine eutectic structure is accompanied by the formation of low-angle grain boundaries (LAGBs), which is also the region where deformed grains gather, giving rise to improved mechanical strengthening.
Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA polymerase (RNAP) through a binding site and ...mechanism that are different from those of current antibacterial drugs. Thus, the ripostatins serve as starting points for the development of new anti‐infective agents with a novel mode of action. In this work, several derivatives of ripostatins were produced. 15‐Desoxyripostatin A was synthesized by using a one‐pot carboalumination/cross‐coupling. 5,6‐Dihydroripostatin A was constructed by utilizing an intramolecular Suzuki cross‐coupling macrolactonization approach. 14,14′‐Difluororipostatin A and both epimeric 14,14′‐difluororipostatins B were synthesized by using a Reformatsky type aldol addition of a haloketone, Stille cross‐coupling, and ring‐closing metathesis. The RNAP‐inhibitory and antibacterial activities are presented. Structure–activity relationships indicate that the monocyclic keto‐ol form of ripostatin A is the active form of ripostatin A, that the ripostatin C5–C6 unsaturation is important for activity, and that C14 geminal difluorination of ripostatin B results in no loss of activity.
F makes the difference: The introduction of a gem‐difluorine substitution into the antibiotic ripostatin B produced an analogue with full activity and increased stability (see scheme; IC50: half maximal inhibitory concentration). The synthesis features the application of a double Stille cross‐coupling/ring‐closing metathesis strategy. Several other ripostatin analogues also were prepared and evaluated.
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