Synthesis, Analytical Characterization, and Human CB Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA.

Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB receptors (hCB), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet-visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described.

Short and Efficient Synthesis of the Antituberculosis Agent Pretomanid from ()-Glycidol.

An efficient gram-scale synthesis of the antituberculosis agent pretomanid using straightforward chemistry, mild reaction conditions, and readily available starting materials is reported. Four different protecting groups on the glycidol moiety were investigated for their technical feasibility and ability to suppress side reactions. Starting from readily available protected ()-glycidols and 2-bromo-4-nitro-1-imidazole, pretomanid could be prepared in a linear three-step synthesis in up to 40% isolated yield.

Pharmacology, prevalence in Germany, and analytical data of cyclobutylmethyl- and norbornylmethyl-type synthetic cannabinoid receptor agonists.

Synthetic cannabinoid receptor agonists (SCRAs) are distributed on the drug market to produce THC-like effects while evading routine drug testing and legislation. The cyclobutylmethyl (CBM) and norbornylmethyl (NBM) side chain specifically circumvented the German legislation and led to the emergence of exploratory SCRAs in 2019-2021. The NBM SCRAs were detected post-amendment of the new psychoactive substances act in 2020, which scheduled all CBM SCRAs.

Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline.

Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation-addition sequence that enable a higher yielding and therefore more economical synthesis of bedaquiline. Prioritization of mechanistic understanding and multi-lab reproducibility led to optimized reaction conditions that feature an unusual base-salt pairing and afford a doubling of the yield of racemic bedaquiline.

Structure elucidation of the novel synthetic cannabinoid Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) found in illicit products in Germany.

New chemical moieties continue to appear in synthetic cannabimimetics (SC), the largest group of new psychoactive substances in the EU. We describe the first comprehensive characterisation of the novel SC Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) (N-[2-phenylpropan-2-yl]-1-tosyl-1H-indazole-3-carboxamide) from seized case samples. Structure elucidation was performed within the EU-project ADEBAR plus to facilitate confident identification by other researchers and practitioners worldwide.

A concise route to MK-4482 (EIDD-2801) from cytidine.

A two-step route to MK-4482 (EIDD-2801, 1) was developed consisting of an esterification and hydroxamination of cytidine. The selective acylation and direct amination eliminate the need for protecting and activating groups and proceed in overall yield of 75%, a significant advancement over the reported yield of 17%. The step count is reduced from five transformations to two, and expensive uridine is replaced with the more available cytidine.

Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones.

Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T.

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt.

A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency.