An Adventurous Synthetic Journey with MNBA from Its Reaction Chemistry to the Total Synthesis of Natural Products

• Shiina Isamu

  Department of Applied Chemistry, Faculty of Science, Tokyo University of Science

Abstract

After initially establishing a novel cyclization reaction of ω-hydroxycarboxylic acids (seco-acids) using 4-trifluoromethylbenzoic anhydride (TFBA) and Lewis acid catalysts to form the corresponding lactones, we discovered a more advanced method for this transformation using 2-methyl-6-nitrobenzoic anhydride (MNBA) as a coupling reagent with nucleophilic catalysts. The latter lactonization is promoted by acyl-transfer catalysts, such as 4-(dimethylamino)pyridine (DMAP), 4-pyrrolidinylpyridine (PPY), and 4-(dimethylamino)pyridine N-oxide (DMAPO). (+)-Ricinelaidic acid lactone ((+)-2) was first synthesized by the TFBA-mediated cyclization with Lewis acid catalysts, while the threo-aleuritic acid lactone (20) was alternatively synthesized by the MNBA-mediated cyclization with acyl-transfer catalysts. Using this effective lactonization technology to form the ester linkage under mild conditions, we then demonstrated the preparation of various large-, medium-, and small-sized natural and unnatural lactones including (−)-cephalosporolide D ((−)-3), (−)-octalactin A ((−)-4), (−)-octalactin B ((−)-25), 2-epibotcinolide (49), (−)- and (+)-2-hydroxytetracosanolides ((−)-77 and (+)-77), (−)- and (+)-2-hydroxy-24-oxooctacosanolides ((−)-78 and (+)-78), (−)-tetrahydrolipstatin ((−)-THL, (−)-117), and the erythromycin A skeletons 103b, 103c, 104c, and 105b. The transition structures involved in the formation of the β-lactones from the corresponding 3-hydroxycarboxylic acids were then determined using DFT calculations at the B3LYP/6-31G*//B3LYP/6-31G* level, and the reactivity of several seco-acids was successfully predicted on the basis of the calculated thermodynamic properties of the transition structures.

Journal

• Bulletin of the Chemical Society of Japan

  Bulletin of the Chemical Society of Japan 87 (2), 196-233, 2014

  The Chemical Society of Japan

Keywords

• General Chemistry

Details

• CRID: 1390001204141127424
• NII Article ID: 130004153271
• DOI: 10.1246/bcsj.20130216
• COI: 1:CAS:528:DC%2BC2cXktFersLw%3D
• ISSN: 13480634
• ISSN: 00092673
• Web Site: https://academic.oup.com/bcsj/article-pdf/87/2/196/56276778/bcsj.20130216.pdf
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed