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Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ1-dehydrogenase (ReM2)-catalyzed Δ1-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring. By strategic use of these three key reactions and fully continuous-flow operations, cyproterone acetate (4) is produced in an overall yield of 9.6% in 3 h of total reaction time, this is the highest total number of chemical transformation performance in any other continuous-flow synthesis reported to date. Flow chemistry has many advantages over batch synthesis of organic small molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, the authors report a 10-step chemobiocatalytic, continuous-flow asymmetric synthesis of cyproterone acetate in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3,17-dione. [ABSTRACT FROM AUTHOR]

Aftobetin is a non‐invasive diagnosis of Alzheimer′s disease, that can bind with aggregated β‐amyloid peptide in eye′s lenses, used for early diagnosis of Alzheimer′s disease in a rapid and painless mode. The reported synthesis of this probe fell short in the aspects of greenness and economy due to the involvement of toxic Chromium(IV) oxidant, noble palladium catalyst, elevated reaction temperature, the long reaction time as well as the cumbersome workup. Herein, a holistic optimization of the synthetic process was achieved via the employment of flow technology and heterogenous photocatalysis. Firstly, the integration of heterogenous carbon nitrides photocatalysis and circulation flow technology furnished the air oxidation of alcohol and nickel catalyzed C−N coupling at 20 g scale, thus avoiding the use of toxic Chromium and precious palladium species respectively. Flow‐intensified esterification between acyl chloride and alcohol, just taking 30 seconds replaced the Steglich esterification of 6 hours, also avoiding the generation of difficult‐to‐remove dicyclohexylurea. Finally, C−N coupling, esterification and Knoevenagel condensation were telescoped together, thus simplifying the reaction workup. This fully‐flow protocol led to the on‐demand synthesis of eight probes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: HpnG plays a crucial role in the production of ribosylhopane, a key intermediate in the biosynthesis of bacteriohopanepolyol. Despite early extensive studies, the precise function of HpnG has remained elusive. Here, we report functional characterization of HpnG as a purine nucleoside phosphorylase, which converts adenosylhopane to phosphoribosylhopane in the presence of phosphate. HpnG demonstrates broad substrate specificity and impressive stability, making it a valuable enzymatic tool for applications in nucleoside processing and related biotechnology. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed enantioselective aminosilylation of alkenes via tandem Aza‐Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri‐substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand. [ABSTRACT FROM AUTHOR]

Owing to its associated advantages such as the generation of two stereocenters in 100% maximum theoretical yield, mild reaction conditions and environmentally friendliness, ketoreductase (KRED)-catalyzed dynamic reductive kinetic resolution (DYRKR) is a versatile and appealing synthetic approach to access valuable chiral alcohols containing two or more stereocenters. Despite the considerable progress that has been made in this research field, previous studies mostly focused on ketone substrates with relatively simple structures. In the present study, ketoreductases YDR368w and YGL039w were identified through enzyme screening and applied to the KRED-catalyzed DYRKR of sterically hindered 2-aryl-1,5-benzothiazepin-3,4(2H,5H)-diones (1). Eleven structurally diverse chiral cis-(2S,3S)-2,3-dihydro-3-hydroxy-2-aryl-1,5-benzothiazepin-4(5H)-ones (cis-(2S,3S)-2), including the critical synthetic intermediates to the calcium channel blockers diltiazem and clentiazem, were prepared in 50–90% isolated yields with excellent stereoselectivities (all >20 : 1 dr and ≥99% ee). Finally, the successful execution of a gram scale synthesis and the demonstrated excellent recyclability of the immobilized ketoreductase (up to 20 cycles) both underscored the good application potential of the currently established DYRKR method. [ABSTRACT FROM AUTHOR]

Covering: 2006 to 2023 (−)-Galantamine is a natural product with distinctive structural features and potent inhibitory activity against acetylcholine esterase (AChE). It is clinically approved for the treatment of Alzheimer's disease. The clinical significance and scarcity of this natural product have prompted extensive and ongoing efforts towards the chemical synthesis of this challenging tetracyclic structure. The objective of this review is to summarize and discuss recent progress in the total synthesis of galantamine from 2006 to 2023. The contents are organized according to the synthetic strategies for the construction of the quaternary center. Key features of each synthesis have been highlighted, followed by a summary and outlook at the end. [ABSTRACT FROM AUTHOR]