Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

Abstract

SummaryKatsumadain A, a naturally occurring influenza virus neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner–Wadsworth–Emmons/oxa Michael addition.

Sustainable Triacetic Acid Lactone Production from Sugarcane by Fermentation and Crystallization

“…The sensitivity analysis performed for the baseline scenario highlighted the significance of operating time and TAL production capacity on the economics of the biorefinery. While the baseline TAL production capacity was 13385 metric ton TAL•y -1 (comparable to the growth projected in the U.S. sorbic acid demand between 2020−2030, comparable to the amount by which the 2019 U.S. demand exceeded the 2019 U.S. production capacity, and equivalent to 50% of the 2019 U.S. sorbic acid demand 11 ), there is significant potential for larger production capacities to meet current and projected U.S. and global demands for a range of potential products for which TAL can serve as a feedstock (including sorbic acid, 2,6 polydiketoenamine plastics, 10 acetylacetone, 2 pogostone, 7 katsumadain, 8 and penicipyrone, 9 among others). Further, there is large uncertainty in the operating schedule for sugarcane biorefineries (e.g., 120−200 annual operating days [41][42][43], and there exists the potential for biorefineries to additionally accept https://doi.org/10.26434/chemrxiv-2024-4sz8x-v2 ORCID: https://orcid.org/0000-0002-2620-2829 Content not peer-reviewed by ChemRxiv.…”

“…Triacetic acid lactone (TAL) has been identified as a bio-privileged chemical-a bio-derived chemical intermediate that can be converted into a diverse set of useful chemical products. [1][2][3][4][5] This utility has motivated recent efforts to investigate the potential use of TAL as a platform chemical in the production of commercially important commodity chemicals (e.g., sorbic acid and potassium sorbate, 2,6 acetylacetone 2 ), specialty chemicals (e.g., pogostone, 7 katsumadain, 8 penicipyrone 9 ), and novel chemicals with the ability to serve as functional replacements to existing products (e.g., highly recyclable and thermally stable polydiketoenamine plastics, 10 enhanced corrosion inhibitors in steel equipment 3 ). In 2019, an estimated 72,350 metric tons of sorbic acid (with a market value of $480 million) was consumed globally, and this demand is projected to grow at 3.8% annually from 2020-2030 (to approximately 104,000 metric ton•y -1 , with a market value of $770 million) largely due to its increasing usage as a preservative in the food and beverage industry.…”

Prevalence of Diarylprolinol Silyl Ethers as Catalysts in Total Synthesis and Patents

“…148 Following their previously reported biomimetic total synthesis of katsumadain C, 149 Tang's group reported the first total synthesis of 125 by employing iminium-ion catalysis. 150 The key element of their synthesis included an organocatalytic enantioselective 1,4-conjugate addition of pyranone 127 to cinnamaldehyde 126 affording adduct 128 in high yield and excellent enantioselectivity (Scheme 28).…”

Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of α,β-Unsaturated Aldehydes

“…In 2013, the Tang group [122] accomplished the first total synthesis of influenza virus neuraminidase inhibitor (−)-katsumadain A (Scheme 45), which had been isolated from the Chinese herbal medicine Alpinia katsumadai Hayata [123] and exhibited antiemetic activity. The above group employed an organocatalytic enantioselective 1,4-conjugate addition for the construction of its benzylic chiral centers.…”