Synthesis of biologically compounds to control of the signal transduction by an application of phophorus functional group

应用磷官能团合成生物化合物来控制信号转导

• 批准号: 12672067
• 负责人: SHIBUYA Shiroshi
• 金额: $ 1.79万
• 依托单位: Tokyo Univ. Pharm. & Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672067/
• 关键词: stereoselective synthesis; punne nucleoside phosphorylase; radical cyclization; Diels-Alder reaction; β-amino acid; chiral catalyst; lipase; hydrophosphinylation; リパーゼ; ディールス-アルダー反応; α-ヘテロ原子置換ホスホン酸; アレン; 細胞内情報伝達系; ヌクレオチドアナログ; プリンヌクレオシドホスホリラー

A variety of biologically active compounds to control of the signal transduction were synthesized. The results can be classified into following items1.A variety of nucleotide analogues having a were cynthesized by condensation of cyclic and acyclic alkyl spacer containing difluoromethylenephosphonic acid moiety were synthesized and condensed with nucleic acid base to get high inhibitory activity to purine nucleoside phosphorylase.2.Sphingomyelin analogous compounds containing difluoromethylenephosphonic acid moiety were synthesized starting with L-serine and D-serine for the evaluation of their inhibitory potency to sphingomyelinase.3.Cyclopropyl carbinols possessing a difluoromethylenephosphonate group were synthesized by reduction of the corresponding ketones.4.Cyclohexane derivative possessing a (diethoxyphosphinyl)difluoromethyl unit were synthesized by the Diels-Alder rection of the 1, 3-butadinene possessing a (diethoxyphosphinyl)difluoromethyl group with dienophiles.5.β-Amino acid derivatives possessing a nucleic acid base were prepared by an application of kinetic resolution of 3-subsituted 1, 3-propane diol as the key reaction.6.Diastereoselective synthesis of chiral β-amino-α-hydroxy-H-phosphinates by hydrophosphinylation of a-amino acids in the prsence of chiral catalyst.

合成了多种具有生物活性的化合物来控制信号转导。主要研究结果如下：1.通过环烷基和非环烷基二氟亚甲基膦酸基团的缩合反应合成了一系列具有α结构的核苷酸类似物，并与核酸碱基缩合得到了对嘌呤核苷磷酸化酶具有较高抑制活性的化合物; 2.以L-丝氨酸和D-丝氨酸为原料，合成了具有α结构的鞘磷脂类似物，并对其进行了结构表征。3.通过还原相应的酮，合成了具有二氟亚甲基膦酸酯基团的环丙基甲醇类化合物4.通过对环己烷衍生物的结构进行分析，确定了它们对鞘磷脂酶的抑制作用（二乙氧基氧膦基）二氟甲基单元通过1，3-丁二烯，具有5.通过应用3-取代的1，6.在手性催化剂存在下，α-氨基酸的氢膦化反应非对映选择性合成手性β-氨基-α-羟基-H-次膦酸酯。

项目成果

Tsutomu Yokomatsu: "1, 3-Dipolar Cycloadition of Diazomethane to, 1, 1-Difluoro-allylphosphonates : Application to Synthesis of Cyclo Propane Derivatives Having a Diethoxyphosphoryldifluoromethylene Unit"Heterocycles. 56. 273-282 (2002)

Tsutomu Yokomatsu：“重氮甲烷到 1, 1-二氟-烯丙基膦酸酯的 1, 3-偶极环加成：在合成具有二乙氧基磷酰基二氟亚甲基单元的环丙烷衍生物中的应用”杂环。

Takehiro Yamagishi: "Diastereoselective Synthesis of Chifal β-Amino-αhydroxy-H-phosphinates though Hydrophos phinylation of α-Amino Aldehydes"Tetrahedron Lett.. Vol.42. 5033-5036 (2001)

Takehiro Yamagishi：“通过 α-氨基醛的氢膦酰化非对映选择性合成 Chifal β-氨基-α羟基-H-次膦酸盐”Tetrahedron Lett.. Vol.42 (2001)。

Tsutomu Yokomatsu: "Synthesis of Aryldifluoromethylphosphothioic Acid from O,O-Diethyl Aryldifluoromethylphosphosphonothioates"J.Organic Chemistry. 65. 5858-5861 (2000)

Tsutomu Yokomatsu：“从O,O-二乙基芳基二氟甲基硫代磷酸酯合成芳基二氟甲基硫代磷酸”J.有机化学。

Tsutomu Yokomatsu: "Synthesis of allenic (α,α-Difluoromethylene) phosphosnates from Propar gylic Tosylates and Acetates Synthesis of allenic (α,α-Difluoromethylene )phosphonates from Propargylic Tosylates and Acetates"Synlett. 287-289 (2000)

Tsutomu Yokomatsu：“从甲苯磺酸丙炔酯和乙酸酯合成联二烯（α，α-二氟亚甲基）磷酸酯从甲苯磺酸丙炔酯和乙酸酯合成联烯（α，α-二氟亚甲基）膦酸酯”Synlett 287-289（2000）。

Tsutomu Yokomatsu: "Diels-Alder Cycloadition of Novel Buta-1,3-dieneDerivatives Prossessing a (Diethoxy-phosphinoyl)-difluoronethyl Unite"Chemical Commun.. 1878-1879 (2001)

Tsutomu Yokomatsu：“新型 Buta-1,3-diene 衍生物的 Diels-Alder 环化反应生成（二乙氧基膦酰基）-二氟乙基单元”Chemical Commun. 1878-1879 (2001)