|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
|Keywords||Biopterin / Glycosidation / Synthesis / D-ribofuranoside / D-glucopyranoside / Selective protection / N,N-Dimethylaminomethylene / p-Nitrophenethyl / L-ビオプテリン / D-リボフラノシル / O^4-(2-P-ニトロフェニルエチル) / N^2-(N,N-ジメチルアミノ)メチレン / N^2,O^4-保護基 / 脱保護-N^2,O^4,1',2' / グリコシド / プテリジン / Dーリボフラノシド / 選択合成 / 保護基 / ジメチルアミノメチレン / pーニトロフェニルエチル|
A certain number of pteridines having a glycosidated side-chain occur in nature. Moreover, glycosides of biopterin and related pteridines are considered to be of interest in view of potent biological activities. Thus, we have explored efficient and versatile glycosidation methods of biopterin and found that an N^2,N(3)-protected biopterin can conveniently be subjected to various reactions including glycosidation.
The reaction of biopterin with N,N-dimethylformamide diethylacetal in DMF at 20ﾟC gave N^2-(N,N-dimethylaminomethylene)-biopterin, which was then converted into the 1',2'-di-O-acetyl derivative. This was led by Mitsunobu reaction to the 3-NPE-biopterin derivative [NPE = p-nitrophenethyl], which, upon methanolysis at 50ﾟC, furnished versatile N^2,N(3)- protected biopterin (PB). This compound is soluble in various nonpolar aprotic solvents and can be subjected to a variety of the diol reactions of the side-chain.
Glycosidation of PB (via di-O-trimethylsilylated PB) was studied by employing 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose as a model substrate, thus affording a mixture of N^2,N(3)-protected biopterin-2'-O-beta-D- ribofuranoside and -1',2'-di-O-beta-D-ribofuranoside, the yields of which depended upon the molar ratio of the sugar donor to PB. Deprotection of these ribosides was performed stepwise. The N(3)-NPE group was cleaved by the action of DBU in DMF, whereas debenzoylation and deamidination were effected by treatment respectively with sodium methoxide in methanol and aqueous methanolic ammonia, thus affording biopterin-2'-O-beta-D-ribofuranoside and -1',2'-di-O-beta-D-ribofuranoside.
Similar results were obtained for glycosidation using a glucopyranose donor to afford biopterin-2'-O-and -1'-O-beta-D-glucopyranoside. Deprotection steps of these glucoside, as well as biological assays of all glycosides obtained, are in progress.