34155-91-4Relevant articles and documents
Biocatalytic Friedel–Crafts Alkylation Using a Promiscuous Biosynthetic Enzyme
Schultz, Erica E.,Braffman, Nathaniel R.,Luescher, Michael U.,Hager, Harry H.,Balskus, Emily P.
supporting information, p. 3151 - 3155 (2019/02/24)
The Friedel–Crafts alkylation is commonly used in organic synthesis to form aryl–alkyl C?C linkages. However, this reaction lacks the stereospecificity and regiocontrol of enzymatic catalysis. Here, we describe a stereospecific, biocatalytic Friedel–Crafts alkylation of the 2-position of resorcinol rings using the cylindrocyclophane biosynthetic enzyme CylK. This regioselectivity is distinct from that of the classical Friedel–Crafts reaction. Numerous secondary alkyl halides are accepted by this enzyme, as are resorcinol rings with a variety of substitution patterns. Finally, we have been able to use this transformation to access novel analogues of the clinical drug candidate benvitimod that are challenging to construct with existing synthetic methods. These findings highlight the promise of enzymatic catalysis for enabling mild and selective C?C bond-forming synthetic methodology.
Alkylresorcylic acid synthesis by type III polyketide synthases from rice Oryza sativa
Matsuzawa, Miku,Katsuyama, Yohei,Funa, Nobutaka,Horinouchi, Sueharu
experimental part, p. 1059 - 1067 (2011/03/20)
Alkylresorcinols, produced by various plants, bacteria, and fungi, are bioactive compounds possessing beneficial activities for human health, such as anti-cancer activity. In rice, they accumulate in seedlings, contributing to protection against fungi. Alkylresorcylic acids, which are carboxylated forms of alkylresorcinols, are unstable compounds and decarboxylate readily to yield alkylresorcinols. Genome mining of the rice Oryza sativa identified two type III polyketide synthases, named ARAS1 (alkylresorcylic acid synthase) and ARAS2, that catalyze the formation of alkylresorcylic acids. Both enzymes condensed fatty acyl-CoAs with three C2 units from malonyl-CoA and cyclized the resulting tetraketide intermediates via intramolecular C-2 to C-7 aldol condensation. The alkylresorcylic acids thus produced were released from the enzyme and decarboxylated non-enzymatically to yield alkylresorcinols. This is the first report on a plant type III polyketide synthase that produces tetraketide alkylresorcylic acids as major products.
