Simple Preparation of Acyclic Adenylate and Its Inhibitory Activity of Protein Synthetase

2‘-5’寡腺苷酸（2-5 A）是一种强的蛋白质合成酶抑制剂。2-5 A被认为是激活核糖核酸酶L （RNase L）来切割m RNA，从而抑制蛋白质合成酶。此后，许多研究小组对野生型2-5 A的制备进行了研究。然而，2-5 A很容易被磷酸核酸酶裂解。半值周期为2 ~ 3分钟。如果克服了这一弱点，2-5 A将成为具有免疫激活剂的强效抗病毒药物的候选物。为了制备2-5 A样的丙烯酸低聚腺苷酸酯，研究了以下三种制剂。1)以1,3 -二恶氧烷为原料成功制备了磷酸腺苷酸酯。2)以双- 1,3 -二恶氧烷为原料，采用一锅反应制得二核苷。3)通过硫链取代膦酸盐制备低聚二恶氧烷制备低聚腺苷酸酯，但从二醇和羟醛中分离的中间产物二恶氧烷尚未大规模分离。正在调查进一步的准备工作。

2'-5' Oligo adenylate (2-5 A) found in the cell cultured extract from inferferon treated with virus is a strong inhibitor of protein synthetase. 2-5 A is considered to activate ribonuclease L (RNase L) to cleave m RNA resulting in inhibiting protein synthetase. Since then, preparation of wild type 2-5 A have been investigated by many group. However, 2-5 A is easily subject to cleavage of phosphate with nuclease. The half-value period has 2-3 minutes. If this weak point is overcome, 2-5 A will be a candidate of a potent anti-virus agent with immune activator. To prepare 2-5 A like acydlic oligoadenylate, the three following preparations were investigated.1) Adenyl phosphonate was successfully prepared from 1, 3-dioxolane.2) Dinucleosides were obtained from bis-1, 3-dioxolane by one-pot reaction.3) Preparation of oligoadenylate from oligodioxolane was examined by substitution of phosphonate with sulfur linkage, but the intermediate dioxolane from diol and hydroxyaldehyde has not been isolated in large scale. Further preparation is being investigated.