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1. Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

   https://doi.org/10.1038/s41467-021-25513-7  

   Hou, Bao-Long; Wong, Jonathan J.; Lv, Na; Wang, Yong-Qiang; Houk, K. N.; Li, Chuang-Chuang (December 2021, Nature Communications)

   Abstract Bridged medium-sized bicyclo[m.n.2] ring systems are common in natural products and potent pharmaceuticals, and pose a great synthetic challenge. Chemistry for making bicyclo[m.n.2] ring systems remains underdeveloped. Currently, there are no general reactions available for the single-step synthesis of various bridged bicyclo[m.n.2] ring systems from acyclic precursors. Here, we report an unusual type II intramolecular (3+2) dipolar cycloaddition strategy for the syntheses of various bridged bicyclo[m.n.2] ring systems. This rhodium-catalysed cascade reaction provides a relatively general strategy for the direct and efficient regioselective and diastereoselective synthesis of highly functionalized and synthetically challenging bridged medium-sized polycyclic systems. Asymmetric total synthesis of nakafuran-8 was accomplished using this method as a key step. Quantum mechanical calculations demonstrate the mechanism of this transformation and the origins of its multiple selectivities. This reaction will inspire the design of the strategies to make complex bioactive molecules with bridged medium-sized polycyclic systems. 

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2. Total Synthesis of UCS1025A via Tandem Carbonylative Stille Cross Coupling and Diels‐Alder Reaction ^†

   https://doi.org/10.1002/cjoc.202300331  

   Cui, Chengsen; Dai, Mingji (August 2023, Chinese Journal of Chemistry)

   Comprehensive Summary We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra‐epi‐UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, from which members with potent antibacterial, antifungal, and anticancer activities have been identified. Our approach features a tandem carbonylative Stille cross coupling and Diels‐Alder reaction to forge a key C—C bond and build thetrans‐decalin system. This tandem process utilizes carbon monoxide as a one‐carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels‐Alder cyclization. Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone‐containing polyketides. 

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3. Enantioselective Synthesis of (−)‐Halenaquinone

   https://doi.org/10.1002/anie.201805370  

   Goswami, Subir; Harada, Kenichi; El‐Mansy, Mohamed F.; Lingampally, Rajinikanth; Carter, Rich G. (June 2018, Angewandte Chemie International Edition)

   Abstract The efficient, 12–14 step (LLS) total synthesis of (−)‐halenaquinone has been achieved. Key steps in the synthetic sequence include: (a) proline sulfonamide‐catalyzed, Yamada–Otani reaction to establish the C6 all‐carbon quaternary stereocenter, (b) multiple, novel palladium‐mediated oxidative cyclizations to introduce the furan moiety, and (c) oxidative Bergman cyclization to form the final quinone ring. 

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4. Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

   https://doi.org/10.1002/slct.202004196  

   Parella, Ramarao; Jakkampudi, Satish; Zhao, John_C‐G (March 2021, ChemistrySelect)

   Abstract Natural products are the great sources of drugs and leading compounds in drug discovery, as it has been estimated that most of the current medicines are derived from natural products. Total synthesis of natural products, especially those of biological activities, has been an important part of organic chemistry, which, besides its potential practical utilities, also provides new inspirations and novel synthetic methodologies. Over the past two decades, organocatalysis has been shown to be very effective in controlling the stereochemistry of the reaction products and has found many applications in the asymmetric synthesis of natural products and related compounds. In this review we will attempt to summarize some applications of asymmetric organocatalysis in the total synthesis of natural products and related compounds in the past seven years. 

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5. Total Synthesis and Antibacterial Investigations of 1‐Hydroxyboivinianin A

   https://doi.org/10.1002/cmdc.202200363  

   Wilt, Ingrid_K; Demeritte, Adrian_R; Wang, Weiwei; Wuest, William_M (October 2022, ChemMedChem)

   Abstract Synthetic investigations of natural products has been instrumental in the development of novel antibacterial small molecules. 1‐hydroxyboivinianin A, a lactone containing phenolic bisabolane isolated from marine sediment, has reported antibacterial activity against the aquatic pathogenVibrio harveyi. The total synthesis of 1‐hydroxyboivinianin A and its enantiomer was completed in a six‐step sequence in 42 % overall yield. The synthesis leveraged a key diastereoselective nucleophilic addition with chiral imidazolidinone to establish the benzylic tertiary alcohol and intramolecular Horner‐Wadsworth Emmons to furnish the lactone. Both enantiomers were found to have negligible antibacterial activity against a panel of gram‐positive and negative bacteria and minimal antifungal activity against phytopathogens. Investigations of a possiblein vitrolactone hydrolysis to produce an inactive linear acid led to the discovery of a spontaneous cyclization, suggesting the lactone is resistant to hydrolysis and the lactone is not degrading to produce an inactive species. 

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