The utility of Streptococcus mutans undecaprenol kinase for the chemoenzymatic synthesis of diverse non-natural isoprenoids.

Isoprene chemoenzymatic cascades (ICCs) overcome the complexity of natural pathways by leveraging a streamlined two-enzyme cascade, facilitating efficient synthesis of C5-isoprene diphosphate precursors from readily available alcohol derivatives. Despite the documented promiscuity of enzymes in ICCs, exploration of their potential for accessing novel compounds remains limited, and existing methods require additional enzymes for generating longer-chain diphosphates. In this study, we present the utility of Streptococcus mutans undecaprenol kinase (SmUdpK) for the chemoenzymatic synthesis of diverse non-natural isoprenoids.

Orthogonal Enzyme-Substrate Design Strategy for Discovery of Human Protein Palmitoyltransferase Substrates.

Protein palmitoylation, with more than 5000 substrates, is the most prevalent form of protein lipidation. Palmitoylated proteins participate in almost all areas of cellular physiology and have been linked to several human diseases. Twenty-three zDHHC enzymes catalyze protein palmitoylation with extensive overlap among the substrates of each zDHHC member.

Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues.

Prenylated proteins contain C or C isoprenoids linked to cysteine residues positioned near their C-termini. Here we describe the preparation of isoprenoid diphosphate analogues incorporating diazirine groups that can be used to probe interactions between prenylated proteins and other proteins that interact with them. Studies using synthetic peptides and whole proteins demonstrate that these diazirine analogues are efficient substrates for prenyltransferases.

Catalyst Control in Switching the Site Selectivity of C-H Olefinations of 1,2-Dihydroquinolines: An Approach to Positional-Selective Functionalization of Quinolines.

A unique approach to achieve site-selective C-H olefinations exclusively at the C-3- or C-8-positions in the quinoline framework has been developed by catalyst control. Distal C(3)-H functionalization is achieved by using palladium catalysis, whereas proximal C(8)-H functionalization is obtained by employing ruthenium catalysis. Switching the site selectivity within a single substrate directly indicates two diverse pathways, which are operating under the palladium- and ruthenium-catalyzed reaction conditions.

Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides.

A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp)-H functionalization of benzyl nitriles in the presence of activated C(sp)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions.

Product Control using Substrate Design: Ruthenium-Catalysed Oxidative C-H Olefinations of Cyclic Weinreb Amides.

A new class of Weinreb amides has been developed as directing groups for the ruthenium-catalysed regioselective oxidative C-H olefination. The new Weinreb amides successfully inhibit the N-O bond reductive cleavage usually associated with the cationic ruthenium system, thereby keeping intact the synthetic utility of Weinreb amides. Mechanistic studies reveal interesting aspects of the directing group capabilities of Weinreb amides when compared to simple amides of similar structures.

Fujiwara-Moritani Reaction of Weinreb Amides using a Ruthenium-Catalyzed C-H Functionalization Reaction.

The ruthenium-catalyzed Fujiwara-Moritani reaction (oxidative-Heck reaction) of Weinreb amides is reported herein. The reaction affords exclusively ortho-C-H olefination products, has excellent substrate scope and tolerates halogen functionalities, which increase the synthetic utility of the method. A variety of activated olefins as well as styrenes can be employed as coupling partners.

Heteroatom-guided, palladium-catalyzed regioselective C-H functionalization in the synthesis of 3-arylquinolines.

A new approach for the regioselective functionalization of the C-3-position of quinolines is described. The method utilizes heteroatom guided regioselective C-3 palladation followed by arylation via transmetalation with aryl boronic acids to yield 3-aryl-N-acyl-1,2-dihydroquinolines. In a one-pot sequence, N-deacylation followed by aromatization leads to important 3-arylquinolines in good yields.