• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1997 Fiscal Year Final Research Report Summary

Exploitation of an Efficient and Practical Method for the Synthesis of Active Vitamin D_3 Derivatives

Research Project

Project/Area Number 07557290
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Chemical pharmacy
Research InstitutionNagasaki University

Principal Investigator

HATAKEYAMA Susumi  Nagasaki University Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (20143000)

Co-Investigator(Kenkyū-buntansha) KUBODERA Noboru  Chugai Pharmaceutical Co., Ltd.Development Coordination Dep.Deputy Senior Manage, 研開推進部, 副部長
IWABUCHI Yoshiharu  Nagasaki University Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (20211766)
Project Period (FY) 1995 – 1997
Keywordsvitamin D / convergent synthesis / C / D-ring of vitamin D / reductive etherification / A-ring of vitamin D / palladium catalyzed reaction / 20-epi-22-oxavitamin D_3 / ED-71
Research Abstract

Since 1alpha, 25-dihydroxyvitamin D_3 was found to play an important role in the modulation of cell proliferation and differentiation as well as in the maintenance of calcium homeostasis, a great deal of attention has been paid to the synthesis of its structural analogs to separate and improve its each inherent biological activities. In this research, we aimed to develop efficient and practical synthetic methods useful for the convergent synthesis of various vitamin D_3 analogs. Because a convergent approach involving coupling of a A-ring fragment and a C/D-ring fragment is much more beneficial than an approach based on photolysis of cholesta-5,7-diene derivatives due to easy access to its unnatural variants.
Firstly, we have developed an efficient method for the preparation of a C/D-ring fragment for 20-epi-22-oxavitamin D_3 analogs based on TMSOTf catalyzed reductive etherification of a ketone with an alkoxytrimethylsilane in the presence of Et_3SiH.Secondly, we have developed a concise method for the synthesis of A-ring fragments on the basis of the new strategy which centers around palladium (0) catalyzed intramolecular Heck type of reaction of the enol triflate derived from a beta-keto ester. Thirdly, we have succeeded in the first convergent synthesis of 1alpha, 25-dihydroxy-2beta-(3-hydroxypropoxy) vitamin D_3 (ED-71) through coupling of the corresponding A-ring fragment and the C/D-ring fragment.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 畑山 範: "A Facile Stereoselective Route to a C/D-Ring Synthon for 20-Epi-22-oxavitamin D_3 Analogues" J.Chem.Soc.,Chemical Communications. 1959-1960 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 久保寺 登: "活性型ビタミンD誘導体-医薬品開発の過程で合成研究者が担当する多彩な役割" 有機合成化学協会誌. 54. 139-145 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡邉 博義: "Synthetic Studies of Vitamin D Analogs.XXII.Synthesis and Antiproliferation Activity of Putative Metabolites of 1α,25-Dihydroxy-22-oxavitamin D_3" Chemical & Pharmaceutical Bulletin. 44. 2280-2286 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 畑山 範: "Convergent Synthesis of 1α,25-Dihydroxy-2β-(3-hydroxypropoxy)vitamin D_3(ED-71)" Bioorganic & Medicinal Chemistry Letters. 7. 2871-2874 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Susumi Hatakeyama: "A Facile Stereoselective Route to a C/D-Ring Synthon for 20-Epi-22-oxavitamin D_3 Analogues" J.Chem.Soc., Chemical Communications. 1959-1956 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noboru Kubodera: "Active Vitamin D Analogs-Improved and Various Roles by Medicinal Chemists during the Course of Development of Promising Candidates as Useful Medicines" Journal of Synthetic Organic Chemistry, Japan. 54. 139-145 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyoshi Watanabe: "Synthetic Studies of Vitamin D Analogs.XXII.Synthesis and Antiproliferation Activity of Putative Metabolites of 1alpha, 25-Dihydroxy-22-oxavitamin D_3" Chemical & pharmaceutical Bulletin. 44. 2280-2286 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Susumi Hatakeyama: "Convergent Synthesis of 1alpha, 25-Dihydroxy-2b-(3-hydroxypropoxy) vitamin D_3 (ED-71)" Bioorganic & Medicinal Chemistry Letters. 7. 2871-2874 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi