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A cascade Claisen rearrangement of a well-organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst-free and gram-scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized.
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http://dx.doi.org/10.1002/anie.201801612 | DOI Listing |
J Am Chem Soc
August 2025
Molecular Synthesis Center & Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
The first asymmetric total syntheses of (-)-psychotriadine () and its putative congener tetrahydropsychotriadine () were accomplished in 12 and 13 steps, respectively, featuring Meerwein-Eschenmoser-Claisen rearrangement and Fischer indolization/Plancher rearrangement cascade. A stereochemically controllable dearomative ring contraction was utilized to create the vicinal quaternary stereocenters. The absolute configuration was confirmed through X-ray crystallography and >200 mg of (90% enantiomeric excess (ee)) was obtained.
View Article and Find Full Text PDFOrg Lett
August 2025
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Computer-aided substrate design is an effective approach to developing new reactions. Here, we report the dearomative Claisen-type rearrangement along with the construction of a quaternary carbon via comprehensive evaluation of the transition states of virtual substrates. The experimental rearrangement of 2,4,6-trimethyl benzyl alkynyl ether occurs as designed.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
State Key Laboratory of Microbial Technology, Shandong University, No. 72 Binhai Road, Qingdao, Shandong, 266237, China.
The recruitment of catabolic β-oxidation enzyme cascades and their reaction logic for natural product biosynthesis remains underexplored, representing a significant opportunity for synthetic biology to engineer novel pathways for structurally unique metabolites. In this study, the first functional reconstitution of the fungal β-oxidative cascade responsible for assembling the immunosuppressant mycophenolic acid (MPA) is reported. Through in vitro enzyme assays, five peroxisomal enzymes are identified that cooperatively mediate two iterative rounds of side-chain cleavage of the biosynthetic precursor MFDHMP-3C and revealed a key oxidative strategy for pharmacophore formation of MPA.
View Article and Find Full Text PDFJ Org Chem
July 2025
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India.
A microwave-assisted cascade conjugate addition-intramolecular cinnamoyl transfer ("cut and sew") strategy involving 2-hydroxyphenyl--quinone methides (HPQMs) and curcumins, yielding cinnamoyl cinnamates bearing a diarylalkyl moiety in excellent yields and with broad substrate versatility, is reported. Mechanistic studies revealed a cascade Michael-hemiketalization-retro-Claisen reaction resulting in the C-C(CO) bond cleavage of curcumin. Furthermore, the cinnamoyl transfer products are amenable for a variety of synthetic transformations, highlighting their significance and synthetic utility.
View Article and Find Full Text PDFOrg Lett
July 2025
232 Choppin Hall, Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
We report a new method for the enantio- and diastereoselective synthesis of α-allene quaternary centers in fully substituted cyclohexanones at the α-positions. This reaction involves asymmetric 1,2-carbonyl addition to 2--propargyl enones using a mixture of Grignard reagents and the PMP-H8-BINOL ligand. The resulting magnesium alkoxide chelate intermediate then activated the propargyl vinyl ether moiety, thereby triggering a cascade propargyl Claisen rearrangement in a diastereoselective manner.
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