Stereoselective synthesis of the trans-decalin subunit with a defined C1 quaternary chiral center has been achieved by the Pauson-Khand reaction (PKR) as a key step. The developed chemistry offers an alternative to the IMDA reaction that has been used for the syntheses of trans-decalin based biologically active natural products.
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http://dx.doi.org/10.1039/c3cc45170d | DOI Listing |
Nat Commun
December 2024
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
We report a stereo-differentiating dynamic kinetic asymmetric Rh(I)-catalyzed Pauson-Khand reaction, which provides access to an array of thapsigargin stereoisomers. Using catalyst-control, a consistent stereochemical outcome is achieved at C2─for both matched and mismatched cases─regardless of the allene-yne C8 stereochemistry. The stereochemical configuration for all stereoisomers was assigned by comparing experimental vibrational circular dichroism (VCD) and C NMR to DFT-computed spectra.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, and Chemical Biology Center, Peking University, 38 Xueyuan Road, Beijing 100191, China.
J Am Chem Soc
December 2024
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Euphorbialoid A () belongs to the rare diterpenoid family of premyrsinanes and exhibits potent anti-inflammatory effects. The 5/7/6/3-membered carbocycle (ABCD-ring) of contains 11 contiguous stereocenters and seven oxygen-containing functional groups. Moreover, four of the six hydroxy groups of are concentrated in the southern sector and flanked by four structurally different acyl groups.
View Article and Find Full Text PDFJACS Au
November 2024
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
(-)-Bipolarolide D is an ophiobolin-derived sesteterpenoid with a unique tetraquinane (5/5/5/5) tetracyclic skeleton decorated with a diverse set of functionalities. Herein we report a robust, scalable, and efficient total synthesis of this natural product in 1.8% overall yield.
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