[reaction: see text] The tricyclic core of phomactin A was synthesized from 6,6-dimethyl-2-cyclohexen-1-one. Key reactions include the addition of a cyclohexenyllithium reagent to an epoxyaldehyde and a regioselective intramolecular epoxide opening to install the oxadecalin core.
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RSC Adv
January 2025
Department of Organic Chemistry, University of Debrecen Egyetem Square 1 Debrecen 4032 Hungary
Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Laboratory of Medicinal Chemical Biology, Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Suzhou Medical College, Soochow University, 199 Ren'ai Road, Suzhou, 215123, PR China. Electronic address:
Pleurotin (1) is a benzoquinone meroterpenoid known for its wide-spectrum antitumor and antibiotic activities, notably acting as natural inhibitors of the thioredoxin reductase (TrxR). Pleurotin (1) has been chemically synthesized, but only in milligram quantities through at least 13 longest linear steps with 0.8 % overall yield due to its complex structure such as fused hexacyclic core with 8 contiguous stereocenters.
View Article and Find Full Text PDFNat Commun
December 2024
National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan, P.R. China.
Skeleton editing for heteroarenes, especially pyrazoles, is challenging and remains scarce because these non-strained aromatics exhibit inert reactivities, making them relatively inactive for performing a dearomatization/cleavage sequence. Here, we disclose a cycloaddition-induced scaffold hopping of 5-hydroxypyrazoles to access the pyrazolopyridopyridazin-6-one skeleton through a single-operation protocol. By converting a five-membered aza-arene into a five-unit spine of a 6/6 fused-bicyclic, this work unlocks a ring-opening reactivity of the pyrazole core that involves a formal C = N bond cleavage while retaining the highly reactive N-N bond in the resulting product.
View Article and Find Full Text PDFOrg Lett
January 2025
Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
Metabolic blockade-based genome mining of the marine sediment-derived SCSIO 07745 led to the discovery of 11 novel aminoquinolinone alkaloids, oxazoquinolinones A-J (-), characterized by an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, and oxazoquinolinone K (), featuring an unprecedented fused 6/6/6/5 tetracyclic core ring system. Additionally, 5 new biosynthetic intermediates or shunt products (-) and a known metabolite sannanine () were identified. Their structures were elucidated by extensive spectroscopic analyses and a comparison of electronic circular dichroism and single-crystal X-ray diffraction.
View Article and Find Full Text PDFOrg Lett
January 2025
State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
A bioinspired alkylation dearomatization reaction was developed to construct the 5/6/6 fused-spiro tricyclic core framework and spiro-quaternary carbon chiral center. The usage of this approach for assembling these natural products of spirocyclic polycyclic polyprenylated acylphloroglucinols with an octahydrospiro-[cyclohexan-1,5'-indene] core is demonstrated by the first asymmetric total synthesis of highly oxidized hyperbeanol A.
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