Diversely functionalized isoquinolines and their core-embedded heterocyclic frameworks: a privileged scaffold for medicinal chemistry.

Isoquinoline-enrooted organic small-molecules represent a challenging molecular target in the organic synthesis arsenal attributed to their structural diversity and therapeutic importance. Into the bargain, isoquinolines are significant structural frameworks in modern medicinal chemistry and drug development. Consequently, synthetic organic and medicinal chemists have been intensely interested in efficient synthetic tactics for the sustainable construction of isoquinoline frameworks and their derivatives in enantiopure or racemic forms. This review accentuates an overview of the literature on the modern synthetic approaches exploited in synthesising isoquinolines and their core embedded heterocyclic skeletons from 2021 to 2022. In detail, the methodologies and inspected pharmacological studies for the array of diversely functionalized isoquinolines or their core-embedded heterocyclic/carbocyclic structures involving the introduction of substituents at C-1, C-3, and C-4 carbon and N-2 atom, bond constructions at the C1-N2 atom and C3-N2 atom, and structural scaffolding within isoquinoline compounds have been reviewed. This intensive study highlights the need for and relevance of relatively unexplored bioisosterism employing isoquinoline-based small-molecules in drug design.

Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons.

Arynes are a privileged class of reactive intermediates in synthetic organic chemistry, and their unusual reactivities have been the subject of engrossing research interest. Recently, there are many reports on novel aryne-based synthetic innovations as a linchpin approach to accomplish the total synthesis of structurally diverse natural products or their derivatives in a racemic and enantiopure fashion. This review provides an overview of the literature on synthetic strategies, employing arynes as crucial intermediates to construct architecturally intriguing bioactive natural products/derivatives in a period of 2019 to 2022. This study highlights the need to investigate the effective synthesis and search for new biological uses of highly functionalized natural product skeletons.

Natural Product-Derived Chiral Pyrrolidine-2,5-diones, Their Molecular Structures and Conversion to Pharmacologically Important Skeletons.

The versatility of the natural products (2S,3S)- and (2S,3R)-3-hydroxy-5-oxotetrahydrofuran-2,3-dicarboxylic acids (1 and 2), isolated in large amounts from tropical plant sources, has been demonstrated by the construction of 3-substituted and 3,4-disubstituted chiral pyrrolidine-2,5-diones. The absolute configurations of chiral pyrrolidine-2,5-diones have been ascertained using chiroptical spectroscopic methods and/or single-crystal XRD data. A combination of different reaction strategies delivering a diverse matrix of fused heterocyclic ring systems is presented. The pyrrolo[2,1-a]isoquinoline alkaloid (+)-crispine A possesses a wide range of pharmacological activities including antidepressant, antiplatelet, antileukemic, and anticancer activities. The analogues of indolizino[8,7-b]indole alkaloids (+)- and (-)-harmicine show strong antileishmanial, antinociceptive, PDE5-inhibitory, antimalarial, and antiviral activities. The bicyclic furo[2,3-b]pyrrolo skeleton is present in many natural products. Thus, the uniqueness of relatively cheap, naturally occurring chiral 2-hydroxycitric acid lactones as chirons has been demonstrated by the construction of some important molecular skeletons that are otherwise difficult to synthesize.

Hafnia alvei pneumonia: a rare cause of infection in the multimorbid or immunocompromised.

Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.