One-Pot Consecutive Reductive Amination Synthesis of Pharmaceuticals: From Biobased Glycolaldehyde to Hydroxychloroquine

Abstract

Reductive amination plays a paramount role in the synthesis of amines. It is often proposed as a more ecofriendly synthesis process than the traditional S N 2-type reactions of amines as it avoids toxic alkylation reagents such as alkyl halides. This work demonstrates the versatility of the reductive amination reaction via the synthesis of hydroxychloroquine (HCQ), one of the most renowned pharmaceuticals during this coronavirus pandemic. The novel green synthesis strategy is based on three consecutive reductive amination reactions conducted in a one-pot system, avoiding intermediary purification steps. Furthermore, a biobased C 2 platform molecule, glycolaldehyde, was selected as a starting reagent. The newly developed reductive amination pathway was appraised using the CHEM21 Green Metric toolkit and compared with the commercially operating method.

Design and process study of chiral separation of (2S,4S)-1-(tert-butoxy carbonyl)-4-(methoxymethyl) pyrrolidine-2-carboxylic acid for green manufacturing

“…This substantial enhancement in AE can be attributed to the notably reduced solvent quantities in the novel method, further corroborated by the significantly reduced PMI values. 61,62…”

“…† This substantial enhancement in AE can be attributed to the notably reduced solvent quantities in the novel method, further corroborated by the significantly reduced PMI values. 61,62 As illustrated in Table 3, the original approach employs hexane and dichloromethane as the solvent, which is identified as a substance of concern due to its associated safety risks, denoted by a red warning symbol. Additionally, both dicyclohexane and hexane raise significant health and safety concerns, denoted by a red warning symbol.…”

Evaluation of Green Biobased Plasticizers in Poly(vinyl chloride): Sustainability, Thermal Behavior, Mechanical Properties, and Durability

“…The methodologies designed for the preparation of the different plasticizers (TBC, ATBC, and TBPTC) were compared with one another (Tables S5 and S6, Supporting Information) using the CHEM 21 Metric toolkit (Table ). This toolkit was developed to evaluate the sustainability of reactions using a comprehensive and holistic range of criteria and was successfully used in previous works. ,, …”

“…This toolkit was developed to evaluate the sustainability of reactions using a comprehensive and holistic range of criteria and was successfully used in previous works. 51,61,62 Considering these previous reports, our study successfully employed Al 2 (SO 4 ) 3 in H 2 O as a catalytic system for the synthesis of TBC and ATBC starting from citric acid. 45 Similar or slightly lower TBC yields were obtained using Al 2 (SO 4 ) 3 dissolved in H 2 O (80.7%) compared to H 2 SO 4 (84.9%).…”

One-Pot Efficient Bioconversion of Crocetin from Zeaxanthin via a Dual-Enzyme System

“…Artificially designed enzyme cascade platforms have recently been developed as powerful systems for the biomanufacturing of natural products. − Currently, several compounds have been successfully synthesized in vitro using an enzyme cascade such as ginsenoside Rh2, , 4-hydroxyphenylacetic acid, and metaraminol . Generally, enzyme cascade system biomanufacturing provides open systems that allow for easy design, manipulation, and optimization due to the absence of cell walls.…”