(2S,3S)-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenine | 81738-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (2S,3S)-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenine
• 英文别名: [(4S,5S)-5-[(6-aminopurin-9-yl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methanol
• CAS: 81738-95-6
• 化学式: C₁₂H₁₇N₅O₃
• 分子量: 279.299
• InChiKey: SPXMBAQNKYIIRA-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S)-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenine 生成 9H-Purine-9-propanoic acid, 6-amino-alpha-hydroxy-, (alphaR)-
  参考文献：
  名称：

  HOLY, A.

  摘要：

  DOI：
• 作为产物：
  描述：

  (4S,5S)-2,2-二甲基-1,3-二氧戊环-4,5-二甲醇 在 吡啶 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 7.0h， 生成 (2S,3S)-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenine
  参考文献：
  名称：

  HOLY, Antonin, Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 1, p. 173 - 189

  摘要：

  DOI：

文献信息

• Synthesis and antiviral activity of stereoisomeric eritadenines
  作者：Antonín Holý、Ivan Votruba、Erik De Clercq

  DOI：10.1135/cccc19821392

  日期：——

  D-Eritadenine (Ia) and L-eritadenine (IIa) were prepared from 5-(adenin-9-yl)-5-deoxyaldofuranoses or enantiomeric 2,3-disubstituted erythronolactones (VIIIb, c, XIV). Oxidation of methyl 2,3-O-isopropylidene-D-ribofuranoside (IX) with periodate in the presence of ruthenium, followed by acid hydrolysis and reduction with sodium borohydride, afforded L-ribonolactone (XI). Its 2,3-O-isopropylidene derivative was subjected to alkaline hydrolysis, followed by oxidation with periodate, reduction with sodium borohydride and reaction with cyclohexanone to give 2,3-O-cyclohexylidene-L-erythronolactone (XIV). Condensation of [U-¹⁴C]-adenine with VIIIb, followed by acid hydrolysis, afforded [U-¹⁴C-adenine]-D-eritadenine. The threo-eritadenines III and IV were prepared by oxidation of 1-(adenin-9-yl)-1-deoxy-2,3-O-isopropylidenethreitols XVI and XVII with sodium periodate in the presence of ruthenium, followed by acid hydrolysis. Reaction of 9-(2,2-diethoxyethyl)adenine (XIX) with malonic acid gave 4-(adenin-9-yl)-3-butenoic acid (XXI); its methyl ester XXII, prepared by treatment with methanol, was isomerized with triethylamine to give methyl 4-(adenin-9-yl)-2-butenoate (XXIII). Hydroxylation of XXIII with osmium tetroxide afforded the racemic mixture of D- and L-threo-eritadenine (III+ IV). Eritadenines Ia and IIa were active against vaccinia, measles and vesicular stomatitis virus. Eritadenine Ia was also effective against reo- and parainfluenza virus. In general, the antiviral activity of the eritadenines decreased in the order D-erythro (Ia) > L-erythro (IIa) > D- and L-threo (III, IV).

  D-厄利他呋喃核苷（Ia）和L-厄利他呋喃核苷（IIa）是从5-(腺嘌呤-9-基)-5-脱氧醛糖或对映异构的2,3-二取代的赤霉糖内酯（VIIIb, c, XIV）制备而成。使用高碘酸盐在钌的存在下氧化甲基2,3-O-异丙基-D-核糖呋喃苷（IX），随后进行酸水解和硼氢化钠还原，得到L-核糖内酮（XI）。将其2,3-O-异丙基衍生物经过碱水解，随后经过高碘酸盐氧化、硼氢化钠还原和与环己酮反应，得到2,3-O-环己基-L-赤霉糖内酯（XIV）。[U-14C]-腺嘌呤与VIIIb缩合，经过酸水解，得到[U-14C-腺嘌呤]-D-厄利他呋喃核苷。通过高碘酸盐在钌的存在下氧化1-(腺嘌呤-9-基)-1-脱氧-2,3-O-异丙基脱氢醇（XVI）和（XVII），得到threo-厄利他呋喃核苷III和IV。9-(2,2-二乙氧基乙基)腺嘌呤（XIX）与丙二酸反应，得到4-(腺嘌呤-9-基)-3-丁烯酸（XXI）；经过甲醇处理制备其甲酯（XXII），再与三乙胺异构化，得到甲基4-(腺嘌呤-9-基)-2-丁烯酸酯（XXIII）。XXIII的羟化反应得到D-和L-厄利他呋喃核苷的外消旋混合物（III+IV）。厄利他呋喃核苷Ia和IIa对牛痘病毒、麻疹病毒和水疱性口炎病毒具有活性。厄利他呋喃核苷Ia也对副流感病毒和副流感病毒有效。总体而言，厄利他呋喃核苷的抗病毒活性按照D-赤霉糖（Ia） > L-赤霉糖（IIa） > D-和L-threo（III, IV）的顺序递减。
• Structure-activity studies on open-chain analogues of nucleosides: Inhibition of S-adenosyl-L-homocysteine hydrolase and antiviral activity 2. Acid open-chain analogues
  作者：Antonín Holý、Ivan Votruba、Erik De Clercq

  DOI：10.1135/cccc19850262

  日期：——

  Over 50 ω-carboxyalkyl derivatives of adenine and other purine bases were examined for their inhibitory effects on rat liver S-adenosyl-L-homocysteine hydrolase and their antiviral activity. To be an inhibitor of SAH-hydrolase the analogue must contain an adenine base substituted at the position 9 by an ω-carboxyalkyl (C₃-C₅) chain bearing at least one hydroxyl function. The absolute configuration at the side-chain is decisive for the dihydroxy and trihydroxy compounds, but less important for the monohydroxyalkanoic acids. D-Eritadenine (1a) and 3-(adenin-9-yl)-2-hydroxypropanoic acids (12a) are the most potent SAH-hydrolase inhibitors and the only compounds possessing an antiviral activity (against vesicular stomatitis, parainfluenza type 3, reovirus type 1, and vaccinia virus). All these compounds effect a rapid irreversible inactivation of SAH-hydrolase. The esters of 1a and 12a exhibit little, if any inhibitory activity toward the enzyme; they are, however, much more potent antiviral agents than the parent compounds 1a and 12a, most probably acting as prodrugs of the latter. 2-Amino-D-eritadenine, (2R,3R)-5-(adenin-9-yl)-2,3-dihydroxypentanoic acid, 9-(dicarboxymethyl)adenine, 4-(adenin-9-yl)-2-hydroxybutanoic acid, 3-(8-bromoadenin-9-yl)-2-hydroxypropanoic acid and O-carboxymethyl derivatives of 9-(2,3-dihydroxypropyl)- and 9-(2,3,4-trihydroxybutyl)adenine are described as novel compounds.

  对腺嘌呤和其他嘌呤碱的50多个ω-羧基烷基衍生物进行了研究，以评估它们对大鼠肝S-腺苷-L-同型半胱氨酸水解酶的抑制作用和抗病毒活性。要成为SAH-水解酶的抑制剂，类似物必须在位置9处含有一个腺嘌呤碱基，该碱基被一个至少具有一个羟基功能的ω-羧基烷基（C3-C5）链所取代。侧链的绝对构型对二羟基和三羟基化合物至关重要，但对单羟基脂肪酸的重要性较小。 D-厄利他嘌呤（1a）和3-（腺嘌呤-9-基）-2-羟基丙酸（12a）是最有效的SAH-水解酶抑制剂，也是唯一具有抗病毒活性（对水疱性口炎病毒、副流感病毒3型、类风湿病毒1型和天花病毒有效）。所有这些化合物都对SAH-水解酶产生快速不可逆的失活作用。 1a和12a的酯类对酶的抑制活性很小，如果有的话；然而，它们比母体化合物1a和12a更具有强大的抗病毒作用，很可能作为后者的前药。 2-氨基-D-厄利他嘌呤，（2R，3R）-5-（腺嘌呤-9-基）-2,3-二羟基戊酸，9-（二羧甲基）腺嘌呤，4-（腺嘌呤-9-基）-2-羟基丁酸，3-（8-溴腺嘌呤-9-基）-2-羟基丙酸和9-（2,3-二羟基丙基）-和9-（2,3,4-三羟基丁基）腺嘌呤的O-羧甲基衍生物被描述为新化合物。
• Novel synthesis of purine acyclonucleosides possessing a chiral 9-hydroxyalkyl group by sugar modification of 9-D-ribitylpurines
  作者：Kosaku Hirota、Yasunari Monguchi、Hironao Sajiki、Magoichi Sako、Yukio Kitade

  DOI：10.1039/a707193k

  日期：——

  A novel approach to the synthesis of purine acyclonucleosides having chiral carbons in the N9-hydroxyalkyl chain was achieved by using 9-(2,3-O-isopropylidene-D-ribityl)purines 1, which are readily prepared from commercially available purine nucleosides. 9-[(2S,3R)-2,3,4-Trihydroxybutyl]purines 4a and 4b, 9-[(2S,3S)-2,3,4-trihydroxybutyl]purines 6a and 6b, L-eritadenine 8, and its analogue 11 are conveniently synthesized via key intermediates, (2S,3S)-2,3-isopropylidenedioxy-4-(purin-9-yl)butanals 2 prepared by NaIO4 oxidation of diols 1.

  利用 9-(2,3-O-异亚丙基-D-核苷)嘌呤 1，合成了一种在 N9-羟基烷基链中具有手性碳的嘌呤无环核苷的新方法，这种嘌呤核苷很容易从市售的嘌呤核苷中制备出来。9-[(2S,3R)-2,3,4-三羟丁基]嘌呤 4a 和 4b、9-[(2S,3S)-2,3,4-三羟丁基]嘌呤 6a 和 6b、L-丝裂腺嘌呤 8、及其类似物 11 可通过关键的中间体（(2S,3S)-2,3-异亚丙基二氧基-4-(嘌呤-9-基)丁醛 2 通过二元醇 1 的 NaIO4 氧化反应制备）方便地合成。
• Intramolecular Cyclization of Some Acyclic Nucleoside Analogs
  作者：Zlatko Janeba、Antonín Holý、Hana Votavová、Milena Masojídková

  DOI：10.1135/cccc19960442

  日期：——

  Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo[5,4,0]undec-7-ene afforded 4e-O,8-anhydro-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines 9 (derivatives of 1,3-oxazepino[2,3-e]adenine). The CD spectra of optically active stereoisomers of 9 have been studied and it was found that for threo isomers 9a and 9b their character corresponds to 5'-O,8-cycloadenosine. The compounds 9 were also prepared by oxidative cyclization of 9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (7) with lead(IV) acetate in benzene. Reaction of 9-(4-hydroxybutyl)adenine (14) with lead(IV) acetate smoothly afforded the seven-membered ring derivative, 4'-O,8-anhydro-9-(4-hydroxybutyl)adenine (15); no anhydro products with five-, six-, and eight-membered ring were found. 2',3'-O-Isopropylideneinosine (16) reacted with lead(IV) acetate to give 5'-O,8-cyclo-2',3'-O-isopropylideneinosine (17) whereas 9-(4-hydroxybutyl)hypoxanthine (18) afforded no cyclic products.

  立体异构体8-溴-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（8）与浓氨水、氢化钠、叔丁醇钾或1,8-二氮杂双环[5,4,0]十一烯反应，得到4e-O,8-去水-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤9（1,3-噁唑并[2,3-e]腺嘌呤的衍生物）。对9的光学活性立体异构体的CD光谱进行了研究，发现对于threo异构体9a和9b，它们的特征对应于5'-O,8-环腺苷。化合物9也可以通过9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（7）与醋酸铅（IV）在苯中氧化环化制备而成。9-(4-羟基丁基)腺嘌呤（14）与醋酸铅（IV）反应顺利地得到七元环衍生物4'-O,8-去水-9-(4-羟基丁基)腺嘌呤（15）；没有发现五元、六元和八元环的去水产物。2',3'-O-异丙基核苷（16）与醋酸铅（IV）反应，得到5'-O,8-环-2',3'-O-异丙基核苷（17），而9-(4-羟基丁基)次黄嘌呤（18）没有产生环状产物。
• A Novel Approach for the Synthesis of Purine Acyclonucleosides Using 9-D-Ribitylpurines as a Chiral Pool
  作者：Kosaku Hirota、Yasunari Monguchi、Hironao Sajiki、Yukio Kitade

  DOI：10.1055/s-1997-3273

  日期：1997.6

  Facile syntheses of L-eritadenine (8a), (2S,3R)-9-(2,3,4-trihydroxybutyl)purines (4a and 4b), and (2S,3S)-9-(2,3,4-trihydroxybutyl)adenine (6a) were achieved by using 9-D-(2,3-O-isopropylideneribityl)purines (1a and 1b) as a chiral pool

  轻松合成 L-eritadenine (8a)、(2S,3R)-9-(2,3,4-三羟基丁基)嘌呤（4a 和 4b）和 (2S,3S)-9-(2,3,4-)三羟基丁基）腺嘌呤（6a）是通过使用 9-D-（2,3-O-异亚丙基二联基）嘌呤（1a 和 1b）作为手性池获得的