2019 highlights of the structural revision of natural product via total synthesis
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2019 highlights of the structural revision of natural product via total synthesis Zongjia Chen, Mark A. Rizzacasa (✉) School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia
© Higher Education Press 2020
For over a century, chemical synthesis has played an essential role in the structural assignment of natural products. With the development of characterization instrumentation and methods [1], such as nuclear magnetic resonance (NMR), high-resolution mass spectrometry, X-ray crystallography etc., natural product chemists view synthetic chemistry more as an assistive technology and less as a core competence. Contrary to this opinion, the development of synthetic chemistry will continue to be critical in the structural evaluation of natural products. Two comprehensive reviews on natural products with revised structures have already been published [2,3]. Many natural products had their structures reassigned, in particular their stereochemical configurations, by total synthesis in 2019 [4–13]. This paper covers some selected examples. Monocillin VII. Monocillin VII was isolated in 2017 from the rice-grown cultures of a Paecilomyces sp. SC0924 [14]. Key structural elements include a b-resorcylate and a 12-membered macrolactone. The first total synthesis of the monocillin VII was completed by the Mohapatra’s group [15] in which the proposed structure of the natural product was synthesized (Scheme 1). The approach included Sonogashira coupling between 1 and 2, dicobaltization, which change geometry of alkyne and improve the macrolactonisation, and Au-catalyzed hydration, to form the proposed Monocillin VII (4b). Unexpectedly, the synthetic compound showed deviations from the product in the 1H NMR and 13C NMR spectra and optical rotation. They suggested a new revised structure and synthesized the 10′S-isomer by a similar route. Comparison of their 1H and 13C NMR data with the published data for the natural product allowed correction of the originally assigned structure. Biemamides B and D. Biemamides B and D were isolated in 2018 from Streptomyces sp. [16]. These natural products contain a pyrimidine core. The structure was Received May 8, 2020; accepted June 10, 2020 E-mail: [email protected]
originally assigned at C5 to the R absolute configuration. The first synthesis was published by the Ha group [17] and the synthetic compounds were found to be enantiomeric to the natural products (Scheme 2). The route began with a regio- and stereo-selective ring opening of the azididine 5 followed by amidation, cyclization to give the pyrimidinedione 8, which was reduced to free amide and converted to final product ent-8a and ent-8b. The specific rotation and the electronic circular dichroism spectrum of the synthetic compounds where opposite in sign to the natural products. This resulted in the revision of the absolute configuration to (–)-5S for both compounds. Citrafungin A. The alkyl citrate natural product citrafungin A was first iso
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