Synthesis of C2-Alkoxy-Substituted 19-Nor Vitamin D3 Derivatives: Stereoselectivity and Biological Activity

The active form of vitamin D3 (D3), 1a,25-dihydroxyvitamn D3 (1,25D3), plays a central role in calcium and bone metabolism. Many structure–activity relationship (SAR) studies of D3 have been conducted, with the aim of separating the biological activities of 1,25D3 or reducing its side effects, such as hypercalcemia, and SAR studies have shown that the hypercalcemic activity of C2-substituted derivatives and 19-nor type derivatives is significantly suppressed. In the present paper, we describe the synthesis of 19-nor type 1,25D3 derivatives with alkoxy groups at C2, by means of the Julia–Kocienski type coupling reaction between a C2 symmetrical A ring ketone and a CD ring synthon. The effect of C2 substituents on the stereoselectivity of the coupling reaction was evaluated. The biological activities of the synthesized derivatives were evaluated in an HL-60 cell-based assay. The a-methoxy-substituted C2α-7a was found to show potent cell-differentiating activity, with an ED50 value of 0.38 nM, being 26-fold more potent than 1,25D3.

Synthesis of Sulfilimines Enabled by Copper-Catalyzed S-Arylation of Sulfenamides

Herein, an unprecedented synthetic route to sulfilimines via a copper-catalyzed Chan-Lam-type coupling of sulfenamides is presented. A key to success in this novel transformation is the chemoselective S-arylation of S(II) sulfenamides to form the S(IV) sulfilimines, overriding the competitive C-N bond formation that does not require a change in sulfur oxidation state. The mild and environmentally benign catalytic conditions enable broad functional group compability. A variety of diaryl or alkyl aryl sulfilimines could be efficiently prepared. The Chan-Lam coupling procedure could also tolerate alkenylboronic acids as coupling partners to afford alkenyl aryl sulfilimines, a class of scaffolds which cannot be directly synthesized via conventional imination strategies. The benzoyl protecting groups could be conveniently removed from the product which, in turn, could be readily transformed to several S(IV) and S(IV) derivatives.

Concise Large-Scale Synthesis of Tomatidine, A Potent Antibiotic Natural Product

Tomatidine has recently generated a lot of interest amongst the pharmacology, medicine, and biology fields of study, especially for its newfound activity as an antibiotic agent capable of targeting multiple strains of bacteria. In the light of its low natural abundance and high cost, an efficient and scalable multi-gram synthesis of tomatidine has been developed. This synthesis uses a Suzuki–Miyaura-type coupling reaction as a key step to graft an enantiopure F-ring side chain to the steroidal scaffold of the natural product, which was accessible from low-cost and commercially available diosgenin. A Lewis acid-mediated spiroketal opening followed by an azide substitution and reduction sequence is employed to generate the spiroaminoketal motif of the natural product. Overall, this synthesis produced 5.2 g in a single pass in 15 total steps and 15.2% yield using a methodology that is atom economical, scalable, and requires no flash chromatography purifications.

Nitrogen-Based Linkers with a Mesitylene Core: Synthesis and Characterization

Mesitylene was used as a core in seven new tritopic nitrogen containing linkers. Three of the linkers, each containing three nitrile groups, were obtained through Suzuki, Sonogashira and Heck-type coupling reactions. Next, these were converted to tetrazol-5-yl moieties by the cycloaddition of sodium azide to the nitrile functionalities. The last linker, containing three 1,2,3-triazol-4-yl moieties, was synthesized by the Huisgen cycloaddition of phenyl azide to the corresponding alkyne. The latter was obtained via a Corey–Fuchs reaction sequence from the previously reported formyl derivative. As the proof of concept for their potential in MOF design, one of the nitriles was used to build an Ag-based network.

A multifunctional ultrathin flexible bianisotropic metasurface with miniaturized cell size

In this paper, a flexible bianisotropic metasurface possessing omega-type coupling is presented. The designed metasurface behaves differently when excited from either forward (port 1) or back (port 2) sides. It provides an absorption of 99.46% at 15.1 Gigahertz (GHz), when illuminated from port 1, whereas, on simultaneous illumination from port 2, it behaves like a partially reflective surface (PRS). Furthermore, the presented metasurface not only acts as an in-band absorptive surface (port 1) and partially reflective surface (port 2), but it also provides 97% out-of-band transmission at 7.8 GHz. The response of the presented metasurface remains the same for both transverse Electric (TE) and transverse magnetic (TM) polarized wave or any arbitrary linearly polarized wave. Additionally, the response of the metasurface is angularly stable for any oblique incidence up to 45º. The proposed ultrathin flexible metasurface with absorption, partial reflection and out-of-band transmission properties can be used in the Fabry Perrot cavity antenna for gain enhancement with radar cross-section (RCS) reduction both for passband and stop-band filtering, and conformal antenna applications.

Wittig olefination “baking powder”: a hexameric halogen-bonded phosphonium salt cage for encapsulation and mechanochemical transformation of small-molecule carbonyl compounds

We report a hexameric supramolecular cage assembled from the components of a Wittig-type phosphonium salt, held together by charge-assisted R-Br· · ·Br-· · ·Br-R halogen bonds. The cage reliably encapsulates small polar molecules, including aldehydes and ketones, to provide host-guest systems in which components are pre-formulated in a near-ideal stoichiometry for a base-activated Wittig olefination in the solid-state. These pre-formulated solids enable a molecular-level “baking powder” approach for solvent-free Wittig reactions, based on a design of solid-state reactivity in which the host for molecular inclusion also acts as a complementary reagent for the chemical transformation of an array of guests. These host-guest solid-state complexes can also act as supramolecular surrogates to their Wittig olefination vinylbromide products, in a Sonogashira-type coupling that enables one-pot mechanochemical conversion of an aldehyde to an enediyne.