Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(3), С. 357 - 389

Опубликована: Янв. 1, 2024

Abstract The pharmaceutical industry has traditionally employed batch processing as a means of synthesizing active ingredients (APIs) on commercial scale. Batch manufacturing enables API synthesis in large quantities order to meet regulations. Yet, this strategy remains cumbersome, is labor‐intensive, and creates complex logistical networks. In recent decades, gradually eroded American economic competitiveness led the offshoring from United States. Today it estimated that +80% APIs are manufactured overseas. [1] Meanwhile, disruptions Coronavirus Disease (SARS‐CoV‐2) have exacerbated weaknesses global supply chain, culminating with widespread shortages critical life‐saving drugs. [2] These emphasized importance reshoring drug U.S. fostered regulatory landscape seeks advanced methods bolster America's chain resiliency. [3] Recently, increased attention been directed towards continuous enable nonstop production within modular stand‐alone flow systems. Continuous (CM) facilitates automation, offers new avenues process intensification, even in‐line analytical monitoring raw materials packaged products. This better conversion, safety, reduced waste, overall cost savings versus traditional batch‐style processing. rise manufacturing, coupled current landscape, rare window opportunity convert processes into continuous, streamlined systems on‐shore eliminate shortages. review will outline state‐of‐the‐art CM highlight translation chemistry unit operations

Язык: Английский

---

Well-Defined Phosphine-Free Manganese(II)-Complex-Catalyzed Synthesis of Quinolines, Pyrroles, and Pyridines

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(13), С. 8351 - 8367

Опубликована: Июнь 21, 2022

Herein, we report a simple, phosphine-free, and inexpensive catalytic system based on manganese(II) complex for synthesizing different important N-heterocycles such as quinolines, pyrroles, pyridines from amino alcohols ketones. Several control experiments, kinetic studies, DFT calculations were carried out to support the plausible reaction mechanism. We also detected two potential intermediates in cycle using ESI-MS analysis. Based these metal-ligand cooperative mechanism was proposed.

Язык: Английский

---

Manganese(I)-catalyzed asymmetric (transfer) hydrogenation of ketones: An insight into the effect of chiral PNN and NN ligands

Journal of Catalysis, Год журнала: 2023, Номер 418, С. 40 - 50

Опубликована: Янв. 7, 2023

Язык: Английский

---

Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations

ChemCatChem, Год журнала: 2024, Номер 16(14)

Опубликована: Март 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Язык: Английский

---

Manganese‐Catalyzed Mono‐N‐Methylation of Aliphatic Primary Amines without the Requirement of External High‐Hydrogen Pressure

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(13)

Опубликована: Фев. 1, 2024

Abstract The synthesis of mono‐ N ‐methylated aliphatic primary amines has traditionally been challenging, requiring noble metal catalysts and high‐pressure H 2 for achieving satisfactory yields selectivity. Herein, we developed an approach the selective coupling methanol amines, without hydrogen, using a manganese‐based catalyst. Remarkably, up to 98 % with broad substrate scope were achieved at low catalyst loadings. Notably, due weak base‐catalyzed alcoholysis formamide intermediates, our novel protocol not only obviates addition but also prevents side secondary ‐methylation, supported by control experiments density functional theory calculations.

Язык: Английский

---

Chemoselective Hydrogenation of α,β-Unsaturated Ketones Catalyzed by a Manganese(I) Hydride Complex

Organic Letters, Год журнала: 2024, Номер 26(20), С. 4173 - 4177

Опубликована: Май 13, 2024

Here, we report the chemoselective hydrogenation of α,β-unsaturated ketones catalyzed by a well-defined Mn(I) PCNHCP pincer complex [(PCNHCP)Mn(CO)2H] (1). The reaction is compatible with wide variety functional groups that include halides, esters, amides, nitriles, nitro, alkynes, and alkenes, for most substrates occurs readily at ambient hydrogen pressure (1–2 bar). Mechanistic studies deuterium labeling experiments reveal non-cooperative mechanism, which further discussed in this report.

Язык: Английский

---

Dimeric Manganese‐Catalyzed Hydroalkenylation of Alkynes with a Versatile Silicon‐Based Directing Group

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(31)

Опубликована: Июнь 7, 2023

Herein, we present a manganese-catalyzed, branched-selective hydroalkenylation of terminal alkynes, under mild conditions through facile installation versatile silanol as removable directing group. With an alkenyl boronic acid the coupling partner, this reaction produces stereodefined (E,E)-1,3-dienes with high regio-, chemo- and stereoselectivity. The protocol features such room temperature air atmosphere, while maintaining excellent functional group compatibility. resulting 1,3-dienesilanol products serve building blocks, removal allows for synthesis both branched 1,3-dienes downstream reactions, well stereoselective construction linear (E,E,E)- or (E,E,Z)-1,3,5-trienes. In addition, Diels-Alder cycloaddition can smoothly selectively deliver silicon-containing pentasubstituted cyclohexene derivatives. Mechanistic investigations, in conjunction DFT calculations, suggest bimetallic synergistic activation model to account observed enhanced catalytic efficiency good regioselectivity.

Язык: Английский

---

Recyclable and air-stable colloidal manganese nanoparticles catalyzed hydrosilylation of alkenes with tertiary silane

RSC Advances, Год журнала: 2025, Номер 15(3), С. 1776 - 1781

Опубликована: Янв. 1, 2025

The manganese nanoparticles we synthesized demonstrated high catalytic activity, achieving 15 800 TON in the hydrosilylation of alkenes with tertiary silanes, and remained recyclable across multiple cycles.

Язык: Английский

---

Recent Developments in Manganese, Iron and Cobalt Homogeneous Catalyzed Synthesis of Primary Amines via Reduction of Nitroarenes, Nitriles and Carboxamides

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(7), С. 948 - 964

Опубликована: Фев. 18, 2023

Abstract The preparation of primary amines attracts huge attention in the molecular synthetic community. Indeed, play a crucial role chemistry as they are important substructures amount drug molecules, agrochemicals, dyes and materials. Compared to stoichiometric reductions using metal hydride based reagents, catalyzed reduction nitroarenes, nitriles carboxamides appears be an attractive option, mainly when associated first row transition metals such manganese, iron, or cobalt. In this short review, we illustrate progress achieved homogeneous hydrogenation, hydrogen transfer, borrowing hydrosilylation carboxamides. magnified image

Язык: Английский

---

Borrowing Hydrogen β-Phosphinomethylation of Alcohols Using Methanol as C1 Source by Pincer Manganese Complex

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(47), С. 25545 - 25552

Опубликована: Ноя. 14, 2023

Herein, we report a manganese-catalyzed three-component coupling of β-H containing alcohols, methanol, and phosphines for the synthesis γ-hydroxy via borrowing hydrogen strategy. In this development, methanol serves as sustainable C1 source. A variety aromatic aliphatic substituted alcohols could undergo dehydrogenative cross-coupling process efficiently deliver corresponding β-phosphinomethylated alcohol products in moderate to good yields. Mechanistic studies suggest that transformation proceeds sequential manner including catalytic dehydrogenation, aldol condensation, Michael addition, hydrogenation.

Язык: Английский

---