Artificial intelligence designed drug synthesis: One-pot preparation of trans β-lactams and application to cholesterol absorption inhibitor SCH 47949 synthesis

An artificial intelligence designed SCH 47949 synthesis is achieved in a stereoselective manner. The key step contains a stereoselective one-pot construction of the trans β-lactam framework via thermal electrocyclization. N-arylation of the β-lactam ring system and a series of functional group transformations synthesized SCH 47949 in a reasonable chemical yield.     

Rare earth triflates/chlorotrimethylsilane induced activation of triethylamine as a latent acetaldehyde anion: a new synthesis of α,β-unsaturated aldehydes

A synthetic methodology for α,β-unsaturated aldehydes employing rare earth triflate is reported. Activated triethylamine reacts with aldehydes to form two carbon extended aldehydes, which is promoted by a catalytic amount of Yb, Sc, Y, and In(OTf)₃, in the presence of chlorotrimethylsilane. We investigated the conditions applicable to aromatic aldehydes as well as heterocyclic compounds as substrates. A deuterium labeling experiment supported our proposed reaction mechanism.     

Synthesis, structure and assessment of the cytotoxic properties of 2,5-dimethylazaferrocenyl phosphonates

The reaction of lithiated 2,5-dimethylazaferrocene 1 with diethyl chlorophosphate proceeds to give lateral and ring phosphonate products. The products 2 and 3 were characterized by spectroscopic (1H, 31P{1H} NMR, MS, IR) methods and 3 was treated with W(CO)5(thf) to form a crystalline W(CO)5-complex 4 which was characterized by single-crystal X-ray analysis. The new 2,5-dimethylazaferrocenyl phosphonates were transformed into the corresponding N-methyl iodide salts 5 and 6 in quantitative yields. Both salts are water soluble and stable compounds and an analysis of their cytotoxic and anti-proliferative activity was carried out. Compound 6 possesses anti-metabolic activity which exhibited some preference towards the cancerous HeLa cell line over the non-cancerous NIH 3T3 cell line. These new compounds are the first examples of azaferrrocene (i.e. non-ferrocene) derivatives featuring biologically important phosphonate groups. The preliminary studies into cytotoxic activity indicates that as with ferrocene, azaferrocene can also be regarded as a potential source for organometallic anticancer agents, featuring the iron centre in the +2 oxidation state rather than the often utilized ferrocenium +3 species.     

Supramolecular hybrid of metal nanoparticles and semiconducting single-walled carbon nanotubes wrapped by a fluorene-carbazole copolymer

The first approach for the preparation of metal nanoparticle/semiconducting single-walled carbon nanotube (SWNT) hybrids with specified chirality is described. For this purpose, a copolymer of a fluorene derivative with two long-chain alkyl substituents and a carbazole derivative carrying a thiol group was used. The copolymer was found to selectively dissolve (7,6)- and (8,7)SWNTs, as determined by UV/Vis/NIR absorption and Raman spectroscopy and 2D photoluminescence mapping. Gold and silver nanoparticles with diameters of about 3.8 and about 3.2 nm, respectively, were readily attached along the SWNTs by means of coordination bonds between the nanoparticles and the thiol moieties on the copolymer, as revealed by atomic force and electron microscopy studies. The study provides a novel way to design and fabricate metal nanoparticle/semiconducting SWNT hybrids with specific nanotube chirality.     

Convergent total synthesis of (+)-mycalamide A

The details of a convergent total synthesis of (+)-mycalamide A are described. Yb(OTf)3-TMSCl-catalyzed cross-aldol reaction conditions are used to synthesize the right segment of mycalamide A. In this reaction, an acid-sensitive aldehyde reacts with methyl trimethylsilyl dimethylketene acetal without epimerization to provide the desired aldol adduct. Additionally, a tetrahydropyran ring, which is the left segment of mycalamide A, is prepared using a novel one-pot delta-lactone formation methodology. Both segments are constructed from a common starting material, d-mannitol. These segments are then coupled in the presence of BuLi, and the functional groups are transformed to complete the synthesis of (+)-mycalamide A.     

Direct, palladium-catalyzed, multicomponent synthesis of beta-lactams from imines, acid chloride, and carbon monoxide

A new palladium-catalyzed synthesis of 3-amido-substituted beta-lactams is reported. This process involves the one-pot coupling of four components, imines, carbon monoxide, and acid chloride, providing a flexible route to construct this class of heterocycle. The generation of beta-lactams with two different imines can also be accomplished, providing a method to assemble these products with independent control over five separate substituents.     

Purification and characterization of exo-type cellouronate lyase

A bacterial strain, Brevundimonas sp. SH203, has an ability to degrade cellouronate, β-(1→4)-linked polyglucuronic acid sodium salt, which is artificially prepared from regenerated cellulose by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation. In a previous paper, an endo-type cellouronate lyase (CUL-I) has been isolated from the strain. In this paper, we purified another cellouronate lyase, CUL-II, from cell-free extracts of Brevundimonas sp. SH203. CUL-II was a monomeric protein with a molecular mass of 56 kDa by size exclusion chromatography and 62 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and most active at pH 7.5. CUL-II formed monomers in a small quantity from cellouronate without forming any intermediate oligomers, whereas it degraded C4′–C5′ unsaturated cellouronate dimer more easily. Thus, CUL-II behaves as an exo-type lyase in degradation of cellouronate. When CUL-I and CUL-II were simultaneously treated to cellouronate, it was degraded to monomers more efficiently than treatment with one enzyme alone, CUL-I or CUL-II. Hence, cellouronate is synergistically degraded to monomers by Brevundimonas sp. SH203 by endo- and exo-type lyases, CUL-I and CUL-II, respectively.     

Facile synthesis of aryl ether dendrimer from unprotected AB2 building blocks using thionyl chloride as an activating agent

[structure: see text] A novel, rapid, inexpensive, and highly efficient convergent approach for the synthesis of a Fréchet- type aryl ether dendrimer using thionyl chloride has been developed. In this method, the purification of each dendron and a dendrimer occurs by recrystallization, extraction, and precipitation. The MALDI-TOF MS spectrum supported the formation of the G2, G3, and G4 dendrons and the star-shaped G4 dendrimer.