27 Total Synthesis of Siomycin A, a Representative of the Thiostrepton Family of Peptide Antibiotics

• Mori Tomonori

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Higashibayashi Shuhei

  Institute for Molecular Science

• Goto Taiji

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Kohno Mitsunori

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Satouchi Yukiko

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Shinko Kazuyuki

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Suzuki Kengo

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Suzuki Shunya

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Tohmiya Hiraku

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

• Hashimoto Kimiko

  Kyoto Pharmaceutical University

• Nakata Masaya

  Department of Applied Chemistry, Faculty of Science and Technology, Keio University

Bibliographic Information

Other Title

• 27 ペプチド性チオストレプトン系抗生物質シオマイシンAの全合成(口頭発表の部)

Abstract

In 1961, siomycins were isolated from the culture broth of Streptomyces sioyaensis by the Shionogi group. The characteristic structure of this thiostrepton family of peptide antibiotics is the bicyclic structure containing a dehydropiperidine, a dihydroquinoline, four thiazoles, a thiazoline, dehydroamino acids, and a dihydroxyisoleucine. These antibiotics show high activities against Gram-positive bacteria, mycobacteria, and human malaria parasite. Also these antibiotics show immunosuppressive properties. Siomycin A was selected as a synthetic target and divided into the five segments, segments A, B, C, D, and E. The coupling of these five segments and the two cyclization reactions finished the total synthesis of siomycin A. The segment A (the dehydropiperidine portion) was synthesized featuring the coupling between the azomethine ylide and the enantiopure sulfinimine, the subsequent stereoselective reduction of the 6-membered imine, and the regioselective dehydrogenation of the piperidin ring. The segment B (the pentapeptide portion), containing the dihydroxyisoleucine, thiazoline, and dehydroamino acid, was synthesized featuring the β-lactone opening by phenylselenylation, the vinylzinc addition to the chiral sulfinimine, and the Wipf oxazoline-thiazoline conversion method. The segment C (the dihydroquioline portion) was synthesized featuring the modified Reissert-Henze reaction, the homolytic heteroaromatic substitution reaction, the one-pot olefination via the new Matsumura-Boekelheide rearrangement using trifluoromethanesulfonic anhydride and triethylamine, the Katsuki asymmetric epoxidation, the stereoselective addition reaction controlled by the stereocenter of the pen-position, and the regioselective opening of the epoxide function with the L-valine derivertive using catalytic Yb(OTf)_3. The segments D and E (the dehydropeptide portions) was synthesized from two phenylselenoalanines. The consecutive coupling of the segments A, C, and D followed by cyclization between the segments A and D afforded the monocyclic core portion (A-C-D). Finally the total synthesis of siomycin A was achieved by the coupling of this portion and the segment B, followed by the one-pot regioselective cyclization of the resulting coupling product and amidation of the segment E onto the cyclization product.

Journal

• Symposium on the Chemistry of Natural Products, symposium papers

  Symposium on the Chemistry of Natural Products, symposium papers 48 (0), 157-162, 2006

  Symposium on the Chemistry of Natural Products Steering Committee

Details

• CRID: 1390282681054051456
• NII Article ID: 110006682647
• DOI: 10.24496/tennenyuki.48.0_157
• ISSN: 24331856
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed