(1R,4S,5S)-N-acetyl-4-methoxymethyl-3-oxa-6-azabicyclo<3.1.0>hexan-2-one | 147384-43-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1R,4S,5S)-N-acetyl-4-methoxymethyl-3-oxa-6-azabicyclo<3.1.0>hexan-2-one
• 英文别名: (1R,4S,5S)-6-acetyl-4-(methoxymethyl)-3-oxa-6-azabicyclo[3.1.0]hexan-2-one
• CAS: 147384-43-8
• 化学式: C₈H₁₁NO₄
• 分子量: 185.18
• InChiKey: GZKKJJIKLBFDRH-PILSHRGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲基吲哚 、 (1R,4S,5S)-N-acetyl-4-methoxymethyl-3-oxa-6-azabicyclo<3.1.0>hexan-2-one 在 三氟化硼乙醚 作用下， 反应 0.17h， 以35%的产率得到3-Acetamido-2,3-dideoxy-2-C-<3-(1-methylindolyl)>-5-O-methyl-D-arabinonolactone
  参考文献：
  名称：

  Preparation of .beta.-substituted tryptophan derivatives: comparison of the reactivity of N-methylindole toward aziridine-2-lactones and aziridine-2-carboxylic esters and interpretation of results using MNDO calculations

  摘要：

  With the aim of preparing novel beta-functionalized tryptophan derivatives, the reaction of (1S,4S,5R)- N-acetyl-4-(methoxymethyl)-3-oxa-6-azabicyclo[3.1.0]hexan-2-one (4), a newly developed rigid analogue of the synthetically useful aziridine-2-carboxylic esters of type 1, with N-methylindole (6) was studied under acidic (Lewis acid) conditions. N-Methylindole reacted exclusively at C-2 of 4 to give 3-acetamido-2,3-dideoxy-2-C-[3-(1-methylindolyl)]-5-O-methyl-D-xylonolactone (7) in contrast to this nucleophile's known reactivity with aziridine-2-carboxylic esters 1 at C-3 under the same conditions. The desired beta-substituted tryptophan derivative 12 was instead obtained by reacting 6 with the tert-butyldimethylsilyl furanoside precursor of 4 (i.e., 9) followed by desilylation and oxidation of the anomeric hydroxyl function with TPAP. The regioselectivity of aziridine ring opening by 6 was rationalized by comparison of the LUMO coefficients and atomic charge distributions for the reactive centers of the aziridine-2-lactone 4, the aziridine-2-carboxylic ester 16, and the aziridine furanoside 9 in both their ground states and protonated states as determined using MNDO calculations. It was found that (1) protonation of both 4 and 16 causes a large increase in the LUMO coefficients at C-2 and C-3, thereby directing attack by N-methylindole (6), a soft nucleophile, toward these centers via orbital control, as has been experimentally observed; (2) of C-2 and C-3, the higher LUMO coefficient was found at the former position for the N-protonated forms of both 4 and 16, suggesting that C-2 is the preferred site of attack by 6 in both cases. Though this was verified experimentally in the case of lactone 4, the fact that aziridine-2-carboxylic esters (e.g. 16) always react with indoles at C-3 under acidic conditions indicates that in these compounds, steric and/or electrostatic effects rather than orbital considerations determine the course of the reaction; (3) in the case of the N-protonated aziridino furanoside 9, C-3 was calculated to have a higher LUMO coefficient than C-2, in accord with the exclusive attack of 6 at the former position. MNDO calculations thus appear to be a useful tool for the prediction of the reactivity patterns of rigid aziridine structures such as 4 and 9, but are less satisfactory in the case of flexible aziridine-2-carboxylates in which other factors may predominate.

  DOI：

  10.1021/jo00081a025
• 作为产物：
  描述：

  Methyl-5-O-methyl-α-D-lyxofuranosid 在 四丙基高钌酸铵 吡啶 、 盐酸 、 sodium hydroxide 、 氯化亚砜 、 sodium azide 、 2,4-二甲基吡啶 、 4 A molecular sieve 、 四丁基氟化铵 、 N-甲基吗啉氧化物 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 111.0h， 生成 (1R,4S,5S)-N-acetyl-4-methoxymethyl-3-oxa-6-azabicyclo<3.1.0>hexan-2-one
  参考文献：
  名称：

  从d-核糖和d-lyxose立体控制合成氮丙啶-2-内酯

  摘要：

  （1S，4S，5R）-N-乙酰基-4-甲氧基甲基-3-氧杂-6-氮杂双环[3.1.0]己二-2-酮15a（光学上纯的环状氮丙啶-2-羧酸酯的环状类似物）的合成从D-核糖开始进行描述。关键步骤包括由三苯基膦促进的3-叠氮基-2-甲苯磺酰基-D-木呋喃糖苷（10a）转化为其相应的2,3-氮丙啶12a，选择性裂解1-Ot-丁基二甲基甲硅烷基保护基，然后通过TPAP氧化内酯15a的异头半缩醛基。该方法直接适用于D-糖，得到对映体纯的（1R，4S，5S）异构体15a，15b。

  DOI：

  10.1016/s0040-4020(01)80332-x

文献信息

• Stereocontrolled synthesis of aziridine-2-lactones from d-ribose and d-lyxose
  作者：Laurent Dubois、Robert H. Dodd

  DOI：10.1016/s0040-4020(01)80332-x

  日期：1993.1

  The synthesis of (1S,4S,5R)-N-acetyl-4-methoxymethyl-3-oxa-6-azabicyclo[3.1.0]hexan-2-one 15a, an optically pure, cyclic analogue of aziridine-2-carboxylates, is described starting from D-ribose. Key steps include triphenylphosphine-promoted conversion of a 3-azido-2-tosyl-D-xylofuranoside (10a) to its corresponding 2,3-aziridine 12a, selective cleavage of a 1-O-t-butyldimethylsilyl blocking group

  （1S，4S，5R）-N-乙酰基-4-甲氧基甲基-3-氧杂-6-氮杂双环[3.1.0]己二-2-酮15a（光学上纯的环状氮丙啶-2-羧酸酯的环状类似物）的合成从D-核糖开始进行描述。关键步骤包括由三苯基膦促进的3-叠氮基-2-甲苯磺酰基-D-木呋喃糖苷（10a）转化为其相应的2,3-氮丙啶12a，选择性裂解1-Ot-丁基二甲基甲硅烷基保护基，然后通过TPAP氧化内酯15a的异头半缩醛基。该方法直接适用于D-糖，得到对映体纯的（1R，4S，5S）异构体15a，15b。
• Preparation of .beta.-substituted tryptophan derivatives: comparison of the reactivity of N-methylindole toward aziridine-2-lactones and aziridine-2-carboxylic esters and interpretation of results using MNDO calculations
  作者：Laurent Dubois、Anita Mehta、Emmanuelle Tourette、Robert H. Dodd

  DOI：10.1021/jo00081a025

  日期：1994.1

  With the aim of preparing novel beta-functionalized tryptophan derivatives, the reaction of (1S,4S,5R)- N-acetyl-4-(methoxymethyl)-3-oxa-6-azabicyclo[3.1.0]hexan-2-one (4), a newly developed rigid analogue of the synthetically useful aziridine-2-carboxylic esters of type 1, with N-methylindole (6) was studied under acidic (Lewis acid) conditions. N-Methylindole reacted exclusively at C-2 of 4 to give 3-acetamido-2,3-dideoxy-2-C-[3-(1-methylindolyl)]-5-O-methyl-D-xylonolactone (7) in contrast to this nucleophile's known reactivity with aziridine-2-carboxylic esters 1 at C-3 under the same conditions. The desired beta-substituted tryptophan derivative 12 was instead obtained by reacting 6 with the tert-butyldimethylsilyl furanoside precursor of 4 (i.e., 9) followed by desilylation and oxidation of the anomeric hydroxyl function with TPAP. The regioselectivity of aziridine ring opening by 6 was rationalized by comparison of the LUMO coefficients and atomic charge distributions for the reactive centers of the aziridine-2-lactone 4, the aziridine-2-carboxylic ester 16, and the aziridine furanoside 9 in both their ground states and protonated states as determined using MNDO calculations. It was found that (1) protonation of both 4 and 16 causes a large increase in the LUMO coefficients at C-2 and C-3, thereby directing attack by N-methylindole (6), a soft nucleophile, toward these centers via orbital control, as has been experimentally observed; (2) of C-2 and C-3, the higher LUMO coefficient was found at the former position for the N-protonated forms of both 4 and 16, suggesting that C-2 is the preferred site of attack by 6 in both cases. Though this was verified experimentally in the case of lactone 4, the fact that aziridine-2-carboxylic esters (e.g. 16) always react with indoles at C-3 under acidic conditions indicates that in these compounds, steric and/or electrostatic effects rather than orbital considerations determine the course of the reaction; (3) in the case of the N-protonated aziridino furanoside 9, C-3 was calculated to have a higher LUMO coefficient than C-2, in accord with the exclusive attack of 6 at the former position. MNDO calculations thus appear to be a useful tool for the prediction of the reactivity patterns of rigid aziridine structures such as 4 and 9, but are less satisfactory in the case of flexible aziridine-2-carboxylates in which other factors may predominate.