A Biocatalytic Route to Highly Enantioenriched β‐Hydroxydioxinones

Abstract

A novel biocatalytic system to access a wide variety of β-hydroxydioxinones from β-ketodioxinones employing commercial engineered ketoreductases has been developed. This practical system provides a remarkably straightforward solution to limitations in accessing certain chemical scaffolds common in β-hydroxydioxinones that are of great interest due to their diversification capabilities. A few highlights of this system are that it is high yielding, highly enantioselective, and chromatography-free. We have demonstrated both a wide substrate scope and a high degree of scalability.

Cyclopentyl Methyl Ether: An Elective Ecofriendly Ethereal Solvent in Classical and Modern Organic Chemistry

“…report an effective enantioselective strategy that overcomes the typical limitations observed with previously known methods, such as the need for as p 2 centera djacent to the newly formed stereogenic center to geth igh stereoselectivity (Scheme56). [96] Therefore, the use of CPME in phosphate buffer with 10 %i sopropyl alcohol (IPA) in the presence of an engineered ketoreductase allow b-hydroxydioxynones to be obtained from b-keto dioxinones in quantitative yields with an enantiomeric ratio (e.r.) of 99:1 by using al ower catalyst loading.…”

Cyclopentyl Methyl Ether (CPME): A Versatile Eco‐Friendly Solvent for Applications in Biotechnology and Biorefineries

“…These biocatalysts catalyzet he transfer of protons and hydrides from/to the substrates with mediation by cofactors. [32] The use of ac ommercials et of engineered ke-Scheme2.Novozym-435-catalyzed esterification of HMF with levulinic acid in CPME. [31] Optically active b-hydroxydioxinones are valuable building blocksi no rganic chemistry.O ne methodf or their preparation, described in 2017, starts from the corresponding b-ketodioxinones and employs KREDs for their enantioselective reduction (Scheme 4a).…”

“…[31] Optically active b-hydroxydioxinones are valuable building blocksi no rganic chemistry.O ne methodf or their preparation, described in 2017, starts from the corresponding b-ketodioxinones and employs KREDs for their enantioselective reduction (Scheme 4a). [32] The use of ac ommercials et of engineered ke-Scheme2.Novozym-435-catalyzed esterification of HMF with levulinic acid in CPME. [22] Scheme3.Dynamic kinetic resolution of racemic benzoin catalyzedbyl ipaseTLand the chemocatalyst Zr-TUD-1 with CPME as solvent.…”

“…Scheme4.a, b) Bioreductionofb-ketodioxinones( a)[32] and Nelfanivir intermediate (b),[33] catalyzedbyk etoreductasesi npresenceC PME. c) Use of imine reductases for the reduction of harmane in buffer containingC PME [35].…”

Targeted Covalent Inhibition of Telomerase

“…2,3 As telomeres progressively shorten with each cell division cycle, one or more may reach a critical length; the resulting DNA damage response blocks further proliferation and promotes apoptosis or cellular senescence. [4][5][6] Stem cells, embryonic cells, and germ cells overcome this proliferation limit by expressing telomerase, a ribonucleoprotein (RNP) complex that counteracts telomere shortening by synthesizing TTAGGG repeats at chromosome 3' ends. 7 The human telomerase core is composed of an RNA-dependent DNA polymerase, the human telomerase reverse transcriptase (hTERT) 8 , and the human telomerase RNA (hTR) 9 which serves as the template for telomere repeat synthesis.…”