Decoding Directing Groups and Their Pivotal Role in C-H Activation.

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H functionalization has been at the forefront due to the multifarious applications in the development of simple to complex molecular architectures and holds a brilliant prospect in drug development and discovery. Despite been explored tremendously by chemists, this functionalization strategy still enjoys the employment of novel metal catalysts as well metal-free organic ligands. Moreover, the switch to photo- and electrochemistry has widened our understanding of the alternative pathways via which a reaction can proceed and these strategies have garnered prominence when applied to C-H activation. Synthetic chemists have been foraging for new directing groups and templates for the selective activation of C-H bonds from a myriad of carbon-hydrogen bonds in aromatic as well as aliphatic systems. As a matter of fact, by varying the templates and directing groups, scientists found the answer to the challenge of distal C-H bond activation which remained an obstacle for a very long time. These templates have been frequently harnessed for selectively activating C-H bonds of natural products, drugs, and macromolecules decorated with multiple C-H bonds. This itself was a challenge before the commencement of this field as functionalization of a site other than the targeted site could modify and hamper the biological activity of the pharmacophore. Total synthesis and pharmacophore development often faces the difficulty of superfluous reaction steps towards selective functionalization. This obstacle has been solved by late-stage functionalization simply by harnessing C-H bond activation. Moreover, green chemistry and metal-free reaction conditions have seen light in the past few decades due to the rising concern about environmental issues. Therefore, metal-free catalysts or the usage of non-toxic metals have been recently showcased in a number of elegant works. Also, research groups across the world are developing rational strategies for directing group free or non-directed protocols that are just guided by ligands. This review encapsulates the research works pertinent to C-H bond activation and discusses the science devoted to it at the fundamental level. This review gives the readers a broad understanding of how these strategies work, the execution of various metal catalysts, and directing groups. This not only helps a budding scientist towards the commencement of his/her research but also helps a matured mind searching out for selective functionalization. A detailed picture of this field and its progress with time has been portrayed in lucid scientific language with a motive to inculcate and educate scientific minds about this beautiful strategy with an overview of the most relevant and significant works of this era. The unique trait of this review is the detailed description and classification of various directing groups and their utility over a wide substrate scope. This allows an experimental chemist to understand the applicability of this domain and employ it over any targeted substrate.

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs.

Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L from a five-point profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36-72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH <1 µg/L and IGF-I 2.5 µg/L. For patients who entered the extension, 14.8% (95% CI: 8.1-23.9), 12.5% (95% CI: 6.4-21.3), 14.8% (95% CI: 8.1-23.9) and 11.4% (95% CI: 5.6-19.9) had mGH <1 µg/L and IGF-I