EFFICIENT CHEMICAL SYNTHESIS OF NATURAL PTERIN DERIVATIVES

• Project/Area Number: 07045016
• Research Category: Grant-in-Aid for international Scientific Research
• Allocation Type: Single-year Grants
• Section: University-to-University Cooperative Research
• Research Field: 物質変換
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: YAMAMOTO Hiroshi OKAYAMA UNIVERSITY,FACULTY OF SCIENCE,PROFESSOR, 理学部, 教授 (70032828)
• Co-Investigator(Kenkyū-buntansha): フライデラー W コンスタンツ大学, 化学部・(ドイツ), 教授 ; HANAYA Tadashi OKAYAMA UNIVERSITY,CENTER OF INSTRUMENTAL ANALYSIS,ASSOCIATE PROFESSOR, 機器分析センター, 助教授 (70189588) ; PFLEIDERER Wolfgang UNIVERSITY OF KONSTANZ,FACULTY OF CHEMISTRY,PROFESSOR ; フライデラー W. ドイツ, コンスタンツ大学・化学部, 教授
• Project Period (FY): 1995 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥2,400,000 (Direct Cost: ¥2,400,000); Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: Biopterin / Glycosylation / Selective reaction / Tetrahydro derivative / Catalytic hydrogenation / Glucoside / Riboside / Limipterin / グルコシル体 / D-グルコサミン / 保護基 / D-グルコピラノシド / 合成

Research Abstract

1. Detaild investigation of a convenient and preparative synthetic scheme for N2- (N,N-dimethyl-aminomethylene) -3- (p-nitrophenethyl) -biopterin, its dihydro and tetrahydro derivatives. [1] 1'-and 2'-beta-D-Glucopyranosyl derivatives were efficiently obtained by employing the above-mentioned N2, N3-protected biopterin a key intermediate, which was successively tetramethylsilylated and then subjected to glycosylation in dichloromethane in presence of stannic chloride. Use of 2.5 equivalent mole of glycosyl donor conveniently afforded the 1', 2'-di-O-glucosyl derivative. [2] Similarly obtained was the 2'-O-beta-D-ribofuranosyl biopterin derivative in a relatively high overall yield. [3] A natural product limipterin {2'-O-beta-D- (N-acetylglucosaminyl) -biopterin} was efficiently synthesized in a similar manner by employing 1,3,4,5-tetra-O-acetyl-2-N- (N,N-phthaloyl) -beta-D-glucosamine as the sugar donor. [4] Catalytic hydrogenation of these N2- (N,N-dimethylaminomethylene) -3- (p-nitrophenethyl) -biopterin in ethyl acetate in the presence of platinum conveniently afforded their tetrahydro derivatives as the main products, suggesting that the present synthetic scheme would be useful in preparation of a series of glycosylated biopterins.
2,3. Chemical synthesis of sepiapterin and its derivatization by selective glycosylation and alkylation, as well as overall and detailed structure-activity relationship of biopterin derivatives are currently under intensive study. Physiological assay of the above-mentioned newly abtained products is also in progress.

Research Products

• [Publications] 花谷 他: "Synthesis of 1'-O-, 2'-O- and l',2'-Di-O-(β-D-glucopyranosyl)-L-biopterin," Chem.Biol.Pteridines and Folates. 49-52 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 花谷 他: "The effect of phosphorus atom upon vicinal 1H-1H coupling constants in pyranose derivatives having a C-P bond. Additivity rule for the effect of phosphorus substituents," Carbohydr.Res.,. (in press). (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Hanaya, K.Soranaka, H.Yamamoto, W,Pfleiderer: "Synthesis of 1'-O-, 2'-O-and 1', 2'-Di-O- (beta-D-glucopyranosyl) -L-biopterin" Chem.Biol.Pteridines and Folatesed. By W.Pfleiderer and H.Rokos, Blackwell Science, Berlin. 49-52. (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T.Hanaya and H.Yamamoto: "The effect of phosphorus atom upon vicinal 1H-1H coupling constants in pyranose derivatives having a C-P bond. Additivity rule for the effect of phosphorus substituents" Carbohydr.Res.(in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 花谷 他: "Synthesis of 1'-O-,2'-O-and 1',2'-Di-O- (β-D-glucopyranosyl) -L-biopterin." Chem.Biol.Pteridines and Folates. 49-52 (1997)
• [Publications] 花谷 他: "The effect of phosphorus atom upon vicinal IH-IH coupling constants in pyranose derivatives having a C-P bond.Additivity rule for the effect of phosphorus substituents." Carbohydr.Res.(in press). (1998)
• [Publications] H.Yamamoto他: "An Efficient Synthesis of Limipterin [2'-O-(2-Acet-amido-2-deoxy-β-D-glucopyranosil)-L-biopterin]via N^2(N,N-Dimethylamino)methylene-3-[2-(4-nitrophenyl)ethyl]-L-biopterin" Pteridines. 7. 110-112 (1996)
• [Publications] T.Hanaya 他: "Selective N(3)- and O4-Alkylation of L-Biopterin : A Convenient Synthesis of 3- and O4-Methyl-L-biopterin and Versatile N2- (N,N-dimethylaminomethylene) -N(3)-p-nitrophen" Pteridines. 6. 1-7 (1995)