BINAP-CuH-catalysed enantioselective allylation using alkoxyallenes to access 1,2-,-diols.

Herein, we present an economical method for highly enantioselective and diastereoselective Cu-BINAP-catalysed reductive coupling of alkoxyallenes with a range of electronically and structurally diverse ketones to afford 1,2-,-diols, using PMHS as the hydride source. This reductive coupling has also been efficiently employed in the enantioselective desymmetrization of prochiral cyclic ketones harboring quaternary centres, in high yields with exclusive diastereoselectivity. Density Functional Theory (DFT) calculations are used to elucidate that the reaction is facilitated by a kinetically favourable "open" -enolate copper-alkoxyallene conformer, occurring at a lower Gibbs free energy barrier (by 3.

Site-selective and stereoselective transformations on -quinols & -quinamines.

The intermolecular transformation of simple substrates into highly functionalized scaffolds with multiple stereogenic centers is an attractive strategy in modern organic synthesis. Prochiral 2,5-cyclohexadienones, being stable and easily accessible, are privileged key building blocks for the synthesis of complex molecules and bioactive natural products. In particular, -quinols and -quinamines are important subclasses of cyclohexadienones, having both nucleophilic and electrophilic sites, and can undergo various intermolecular cascade annulations formal cycloadditions and other transformations.

CuH-Catalyzed Enantioselective Desymmetrization of Cyclic 1,3-Diketones.

Herein, we report a CuH-catalyzed asymmetric desymmetrization of prochiral cyclopentane-1,3-diones to access cyclic 3-hydroxy ketones having an all-carbon quaternary center with high diastereoselectivity via hydrosilylation using PMHS as an inexpensive hydride source. This reaction displays high functional group tolerance including reducible alkyne, alkene, and ester groups with a broad substrate scope. The importance of chiral cyclic 3-hydroxy ketone building blocks was also demonstrated through the synthesis of (-)-estrone, the toxicodenane E core, and fused indoles.

Metal-free oxidative formal C(sp)-H arylation of cyclopentene-1,3-diones with β-naphthols.

An efficient, mild, and transition-metal free formal C(sp)-H arylation of prochiral 2,2-disubstituted cyclopentene-1,3-diones is reported. This oxidative arylation with β-naphthols proceeds base-mediated -Michael addition followed by aerial oxygen insertion and a subsequent α-hydroperoxy elimination sequence. This operationally simple and environmentally benign transformation is highly scalable and does not require any pre-functionalization.

Enantioselective Cu(I)-catalyzed borylative cyclization of enone-tethered cyclohexadienones and mechanistic insights.

The catalytic asymmetric borylation of conjugated carbonyls followed by stereoselective intramolecular cascade cyclizations with in situ generated chiral enolates are extremely rare. Herein, we report the enantioselective Cu(I)-catalyzed β-borylation/Michael addition on prochiral enone-tethered 2,5-cyclohexadienones. This asymmetric desymmetrization strategy has a broad range of substrate scope to generate densely functionalized bicyclic enones bearing four contiguous stereocenters with excellent yield, enantioselectivity, and diastereoselectivity.

Rh(III)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienones C(sp)-H bond activation.

Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienones Rh(III)-catalyzed C-H activation of -methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity.

Bachem - Insights into Innovative and Sustainable Peptide Chemistry and Technology by the Leading Independent Manufacturer of TIDES.

Since its foundation in 1971, Bachem has grown sustainably over the last 50 years and is excellently positioned as the leading company for the development and production of TIDES pep and oligonucleo. Bachem's success relies on its commitment to manufacturing high-quality active pharmaceutical ingredients (APIs) alongside its continual passion for innovative chemistry and technologies. This review aims at summarizing improvements in high-quality peptide manufacturing as well as recent advances towards sustainable and innovative technology in peptide chemistry, thereby reducing the environmental footprint.

Self-assembling tetrameric peptides allow in situ 3D bioprinting under physiological conditions.

We have developed an in situ bioprinting method that allows the printing of cells under true physiological conditions by applying self-assembling ultrashort peptides as bioinks. This method avoids cell stressing methods, such as UV-treatment, chemical crosslinking and viscous bioink printing methods. We further demonstrate that different nanomaterials can easily be synthesized or incorporated in the 3D bioprinted peptide scaffolds which opens up the possibility of functionalized 3D scaffolds.

Diastereoselective Desymmetrization of -Quinamines through Regioselective Ring Opening of Epoxides and Aziridines.

A highly diastereoselective desymmetrization of -quinamines via regioselective ring opening of epoxides and aziridines under mild conditions has been developed. A chairlike six-membered transition state with minimized 1,3-diaxial interactions explains the relative stereoselectivity of the cyclization reaction. This transition-metal free [3 + 3] annulation reaction provides rapid access to fused bicyclic morpholines and piperazines with a tetrasubstituted carbon center in high yields.

Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones via tandem arylative cyclization.

The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.

Remarkable Modulation of Self-Assembly in Short γ-Peptides by Neighboring Ions and Orthogonal H-Bonding.

Gabapentin, an antiepileptic drug, is known to form stable helical structures in short peptides. Distinctly, we report on the newly synthesized γ-analogue of gabapentin, that is, γ-gabapentin (γ-Gpn), which manifests β-sheet character at molecular and nanofibrous hydrogels at the supramolecular level. We investigated the influence of proximally immobilized cationic amino acids (lysine and arginine) on the self-assembly of backbone-expanded tripeptide motif.

Foldamers to nanotubes: influence of amino acid side chains in the hierarchical assembly of α,γ(4)-hybrid peptide helices.

Supramolecular assembly of various artificially folded 12-helical architectures composed of γ(4) -Val, γ(4) -Leu and γ(4) -Phe residues is investigated. In contrast to the 12-helices composed of γ(4) -Val and γ(4) -Leu residues, the helices with γ(4) -Phe residues displayed unique elongated nanotubular architectures. The elongated nanotube assembly was further explored as a template for biomineralization of silver ions to silver nanowires.

Efficient access to enantiopure γ4-amino acids with proteinogenic side-chains and structural investigation of γ4-Asn and γ4-Ser in hybrid peptide helices.

Hybrid peptides composed of α- and β-amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ- and hybrid γ-peptides composed of γ(4) -amino acids are less studied than their β-counterparts. However, recent investigations reveal that γ(4)-amino acids have a higher propensity to fold into ordered helical structures.

γ-Amino acid mutated α-coiled coils as mild thermal triggers for liposome delivery.

The stability and compatibility of designed coiled coil peptides towards the selective incorporation of γ(4)-amino acids at the hydrophobic positions of the heptad repeat are studied. Investigations reveal that the low thermal denaturation temperature of γ(4)-residue mutated coiled coils can be utilized as a mild hyperthermia trigger in liposomes.

Remarkable thermoresponsive nanofibers from γ-peptides.

Conformational analysis of γ-peptides composed of 4,4-gem-dimethyl γ-amino acids, their spontaneous self-assembly into nanofibrillar superstructures and remarkable thermoreversible gelation properties in various organic solvents are studied. This new generation of γ-peptides may serve as potential templates to design advanced biomaterials.

Protein secondary structure mimetics: crystal conformations of α/γ4-hybrid peptide12-helices with proteinogenic side chains and their analogy with α- and β-peptide helices.

Numerous strategies have been developed to mimic the α-helical secondary structure using hybrid peptides containing non-natural amino acids. In contrast to the β- and α/β-hybrid peptides, very little is known about the folding patterns of hybrid peptides containing γ(4)-amino acids. Here we report the solid phase synthesis and crystallographic insight into the secondary structures formed by 1 : 1 alternating α/γ(4)-hybrid peptides.

α/γ(4)-Hybrid peptide helices: synthesis, crystal conformations and analogy with the α-helix.

Synthesis, crystal conformations of α/γ(4)-hybrid peptide helices containing proteinogenic amino acid side-chains, and the analogy with the α-helix are reported. Results suggest that α/γ(4)-hybrid peptides adopted helical conformations with 12-membered H-bond pseudocycles in single crystals.

Copper(II) mediated facile and ultra fast peptide synthesis in methanol.

A novel, ultrafast, mild and scalable amide bond formation strategy in methanol using simple thioacids and amines is described. The mechanism suggests that the coupling reactions are initially mediated by CuSO(4)·5H(2)O and subsequently catalyzed by in situ generated copper sulfide. The pure peptides were isolated in satisfactory yields in less than 5 minutes.

Low-grade malignant proliferating pilar tumor simulating a squamous-cell carcinoma in an elderly female: a case report and immunohistochemical study.

A 65-year-old lady presented with an ulcerated lesion over the occipital region of nine-year duration, an incisional biopsy of which was reported as squamous-cell carcinoma. A wide local excision was performed and the tissue was sent for histopathological examination which revealed a low-grade malignant pilar tumor. Focal invasion and atypia were noted.

Synthesis of α, β-unsaturated γ-amino esters with unprecedented high (E)-stereoselectivity and their conformational analysis in peptides.

Mild, efficient and racemization-free synthesis of N-protected α, β-unsaturated γ-amino esters with unprecedented high E- stereoselectivity is described. This method is found to be compatible with Boc-, Fmoc- and other side chain protecting groups. The crystal conformations of the vinylogous γ-amino esters in monomers and in homo- and mixed dipeptides are studied.

A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols.

A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals.

Tin(II) chloride assisted synthesis of N-protected γ-amino β-keto esters through semipinacol rearrangement.

A facile synthetic route for the preparation of N-protected γ-amino β-keto esters from amino aldehydes and ethyl diazoacetate is described. The two component coupling is facilitated by tin(II) chloride followed by semipinacol rearrangement leading to the product in quantitative yield. The reaction is mild, instantaneous and compatible with Boc-, Fmoc- and Cbz-amino protecting groups.