6-fluoro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erytropentofuranosyl)purine | 135560-86-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-fluoro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erytropentofuranosyl)purine
• 英文别名: tert-butyl-[[(2R,3S,5R)-3-[tert-butyl(dimethyl)silyl]oxy-5-(6-fluoropurin-9-yl)oxolan-2-yl]methoxy]-dimethylsilane
• CAS: 135560-86-0
• 化学式: C₂₂H₃₉FN₄O₃Si₂
• 分子量: 482.746
• InChiKey: MGCRVYFAZKWGTA-GVDBMIGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.67
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-fluoro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erytropentofuranosyl)purine 在 吡啶 、 4-二甲氨基吡啶 、 六甲基二硅氮烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (3S,4S)-N6-(4-(3-acetoxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis(tert-butyldimethylsilyl)-2'-deoxyadenosine
  参考文献：
  名称：

  Laksman, Mahesh K.; Sayer, Jane M.; Jerina, Donald M., Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6589 - 6594

  摘要：

  DOI：
• 作为产物：
  描述：

  6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine 、 叔丁基二甲硅基三氟甲磺酸酯 在 吡啶 作用下， 以 乙二醇二甲醚 为溶剂， 反应 0.75h， 以92%的产率得到6-fluoro-9-(2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-β-D-erytropentofuranosyl)purine
  参考文献：
  名称：

  Laksman, Mahesh K.; Sayer, Jane M.; Jerina, Donald M., Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6589 - 6594

  摘要：

  DOI：

文献信息

• Highly Diastereoselective Synthesis of Nucleoside Adducts from the Carcinogenic Benzo[<i>a</i>]pyrene Diol Epoxide and a Computational Analysis
  作者：Mahesh K. Lakshman、John C. Keeler、Felix N. Ngassa、John H. Hilmer、Padmanava Pradhan、Barbara Zajc、Kathryn A. Thomasson

  DOI：10.1021/ja063902u

  日期：2007.1.1

  diastereoselective dihydroxylation wherein phenylboronic acid was a water surrogate. The resulting boronate ester was converted to a tetraol derivative in which two of the four hydroxyl groups (trans 7, 8) were protected as benzoate esters while the remaining two (cis 9, 10) were free. The cis glycol entity was then subjected to a reaction with 1-chlorocarbonyl-1-methylethylacetate to yield an intermediate chloro

  对应于致癌物 (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a 的顺式开环的核苷加合物的非对映选择性合成] 芘 (BaP DE-2) 由 2'-脱氧腺苷和 2'-脱氧鸟苷组成。关键中间体 (+/-)-10alpha-amino-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene 是通过高度非对映选择性二羟基化合成的，其中苯基硼酸是水的替代物。所得硼酸酯转化为四醇衍生物，其中四个羟基中的两个（反式 7、8）被保护为苯甲酸酯，而剩余的两个（顺式 9、10）是游离的。然后使顺式二醇实体与乙酸1-氯羰基-1-甲基乙基酯反应，得到中间体氯单乙酰氧基二苯甲酸酯。用叠氮化物置换卤化物、酯的完全裂解和叠氮化物的催化还
• Palladium-Catalyzed Synthesis of Carcinogenic Polycyclic Aromatic Hydrocarbon Epoxide-Nucleoside Adducts:  The First Amination of a Chloro Nucleoside¹
  作者：Mahesh K. Lakshman、Padmaja Gunda

  DOI：10.1021/ol027084w

  日期：2003.1.1

  reactive benzo[a]pyrene bay-region amino benzoates, derived from the tetrahydro and diol epoxides, with C-6 and C-2 halopurine deoxynucleosides offers an efficient approach to the synthesis of the corresponding nucleoside-epoxide adducts. Also reported are the first examples involving the coupling of a 6-chloropurine deoxynucleoside with these amines, a reaction that is difficult by direct halide displacement

  由四氢和二醇环氧化物衍生的轴向受约束的，反应性较低的苯并[a] py海湾区氨基苯甲酸酯与C-6和C-2卤代嘌呤脱氧核苷的Pd催化偶联提供了一种有效的方法来合成相应的核苷-环氧加合物。还报道了涉及6-氯嘌呤脱氧核苷与这些胺的偶联的第一个实例，该反应难以通过直接卤化物置换来进行。还讨论了这种金属催化的CN键形成的某些机理。[反应-见文字]
• Synthesis of deoxyadenosine adducts from the highly carcinogenic fjord region diol epoxide of benzo[c]phenanthrene
  作者：Mahesh K. Lakshman、Herman J.C. Yeh、Haruhiko Yagi、Donald M. Jerina

  DOI：10.1016/s0040-4039(00)60852-3

  日期：1992.11

  Unlike bay-region diol epoxides, the fjord-region benzo[c]phenanthrene 3,4-diol 1,2-epoxide-2(4-hydroxyl and epoxide oxygen trans) undergoes non-regioselective ring opening by both ammonia and azide anion. Adducts corresponding to a benzylic and non-benzylic SN2 ring opening by N6 of deoxyadenosine have been characterized.

  与湾区二醇环氧化物不同，峡湾区苯并[c]菲3,4-二醇1,2-环氧化物-2（4-羟基和环氧化物氧反式）通过氨和叠氮化物阴离子均发生非区域选择性的开环。对应于苄基和非苄型小号加合物Ñ由N 2开环6脱氧腺苷的已被表征。
• Synthesis of Oligonucleotide Adducts of the Bay Region Diol Epoxide Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons
  作者：Hongmee Lee、Ernestina Luna、Michael Hinz、John J. Stezowski、Alexander S. Kiselyo、Ronald G. Harvey

  DOI：10.1021/jo00122a048

  日期：1995.9

  An efficient method for the site-specific synthesis of adducts between the biologically active diol epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and oligonucleotides in which a PAH component of predetermined stereochemistry is linked covalently to the exocyclic amino groups of deoxyadenosine (dA) and deoxyguanosine (dG) is described. The synthetic strategy involves in the key step coupling a protected halopurine derivative with an amino derivative (or an aminotriol derivative) of the PAH. This method was initially employed to prepare the dA and dG adducts of the model PAH 1-methylpyrene. The appropriately protected dA adduct was then incorporated into the oligonucleotide sequence d(GCAGGTCA(*)AGAG) where A(*) represents N6-pyrenylmethyl-dA. This methodology was extended to the synthesis of trans adducts of anti-diol epoxide metabolites of benzo[a]pyrene and 5-methylchrysene linked to the 6-amino function of dA. The parent hydrocarbons are widespread environmental carcinogens. This synthetic approach, dubbed the total synthesis method, complements the direct synthesis method which involves the direct reaction of PAH diol epoxides with oligonucleotides. The total synthesis method is broader in scope than the latter, and it is readily adaptable to the large scale preparation of PAH-oligonucleotide adducts required for structure determination by high resolution NMR and X-ray crystallographic techniques.
• Synthesis and site-specific incorporation of a bay-region cis ring-opened tetrahydro epoxide-deoxyadenosine adduct into a DNA oligomer
  作者：Mahesh K. Lakshman、Jane M. Sayer、Donald M. Jerina

  DOI：10.1021/jo00038a037

  日期：1992.6

  Chemical synthesis of the 1,2,3,4-tetrahydrophenanthrene 3,4-epoxide adducts resulting from benzylic, cis ring-opening of the epoxide by the exocyclic amino group of 2'-deoxyadenosine (dA) is described. The approach taken consists of coupling (+/-)-cis-3-hydroxy-4-amino-1,2,3,4-tetrahydrophenanthrene with a 6-fluoro analogue of dA in which the furanose hydroxyl groups are protected. The required amino alcohol was obtained by reaction of 1,2-dihydrophenanthrene with osmium tetraoxide to form the cis 3,4-diol, conversion to the trans chlorohydrin benzoate via its orthobenzoate, displacement of the benzylic chloride by azide, hydrolysis to the cis azido alcohol, and reduction to the racemic cis amino alcohol. Coupling of the amino alcohol with the 3',5'-bis-O-(tert-butyldimethylsilyl) derivative of 6-fluoro-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine results in a pair of diastereomers that are readily separated by HPLC on silica gel. Replacement of the previously used pyridine by 2,6-lutidine significantly improved the yield for the coupling step. Both adducts were acetylated on the hydroxyl group of the hydrocarbon and then desilylated on the sugar. Absolute configurations were assigned to the adducts on the basis of the shapes of their CD spectra. The 3S,4R diastereomer (derived from the more polar, late-eluting adduct) was blocked at the 5'-sugar hydroxyl group with the 4,4'-dimethoxytrityl group and allowed to react with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite to produce the desired activated nucleoside. Incorporation into the deoxynucleotide TpGpA*pGpT as the central base proceeded in good yield with minor modifications to the standard DNA synthesizer protocol.