diethyl 2-acetyl-2,4-dimethylglutarate | 85373-81-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: diethyl 2-acetyl-2,4-dimethylglutarate
• CAS: 85373-81-5
• 化学式: C₁₃H₂₂O₅
• 分子量: 258.315
• InChiKey: LCRHCUDFXNGQHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  69.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diethyl 2-acetyl-2,4-dimethylglutarate 在 盐酸 作用下， 以 水 为溶剂， 生成 2,4-dimethyl-5-ketohexanoic acid
  参考文献：
  名称：

  Mechanism and Stereospecificity of a Fully Saturating Polyketide Synthase Module: Nanchangmycin Synthase Module 2 and Its Dehydratase Domain

  摘要：

  Recombinant nanchangmycin synthase module 2 (NANS module 2), with the thioesterase domain from the 6-deoxyerythronolide B synthase (DEBS TE) appended to the C-terminus, was cloned and expressed in Escherichia coli. Incubation of NANS module 2+TE with (+/-)-2-methyl-3-keto-butyryl-N-acetylcysteamine thioester (1), the SNAC analog of the natural ACP-bound substrate, with methylmalonyl-CoA (MM-CoA) in the absence of NADPH gave 3,5,6-trimethy1-4-hydroxypyrone (2), identified by direct comparison with synthetic 2 by radio-TLC-phosphorimaging and LC-ESI(+)-MS-MS. The reaction showed K(cat) 0.5 +/- 0.1 min(-1) and K(m)(1) 19 +/- 5 mM at 0.5 mM MM-CoA and k(cat)(app) 0.26 +/- 0.02 min(-1) and K(m)(MM-CoA) 0.11 +/- 0.02 mM at 8 mM 1. Incubation in the presence of NADPH generated the fully saturated triketide chain elongation product as a 5:3 mixture of (2S,4R)-2,4-dimethy1-5-ketohexanoic acid (3a) and the diastereomeric (2S, 4S)-3b. The structure and stereochemistry of each product was established by comparison with synthetic 3a and 3b by a combination of radio-TLC-phosphorimaging and LC-ESI(-)-MS-MS, as well as chiral capillary GC-MS analysis of the corresponding methyl esters 3a-Me and 3b-Me. The recombinant dehydratase domain from NANS module 2, NANS DH2, was shown to catalyze the formation of an (E)-double bond by syndehydration of the ACP-bound substrate anti-(2R,3R,4S,5R)-2,4-dimethyl-3,5-dihydroxyheptanoyl-ACP6 (4), generated in situ by incubation of (2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][AT6] didomain and ACP6 from DEBS module 6 along with the ketoreductase from the tylactone synthase module 1 (TYLS KR1). These results also indirectly establish the stereochemistry of the reactions catalyzed by the KR and enoylreductase (ER) domains of NANS module 2.

  DOI：

  10.1021/ja1073432
• 作为产物：
  描述：

  2-acetyl-4-methyl-glutaric acid diethyl ester 、 碘甲烷 在 sodium 作用下， 生成 diethyl 2-acetyl-2,4-dimethylglutarate
  参考文献：
  名称：

  Mechanism and Stereospecificity of a Fully Saturating Polyketide Synthase Module: Nanchangmycin Synthase Module 2 and Its Dehydratase Domain

  摘要：

  Recombinant nanchangmycin synthase module 2 (NANS module 2), with the thioesterase domain from the 6-deoxyerythronolide B synthase (DEBS TE) appended to the C-terminus, was cloned and expressed in Escherichia coli. Incubation of NANS module 2+TE with (+/-)-2-methyl-3-keto-butyryl-N-acetylcysteamine thioester (1), the SNAC analog of the natural ACP-bound substrate, with methylmalonyl-CoA (MM-CoA) in the absence of NADPH gave 3,5,6-trimethy1-4-hydroxypyrone (2), identified by direct comparison with synthetic 2 by radio-TLC-phosphorimaging and LC-ESI(+)-MS-MS. The reaction showed K(cat) 0.5 +/- 0.1 min(-1) and K(m)(1) 19 +/- 5 mM at 0.5 mM MM-CoA and k(cat)(app) 0.26 +/- 0.02 min(-1) and K(m)(MM-CoA) 0.11 +/- 0.02 mM at 8 mM 1. Incubation in the presence of NADPH generated the fully saturated triketide chain elongation product as a 5:3 mixture of (2S,4R)-2,4-dimethy1-5-ketohexanoic acid (3a) and the diastereomeric (2S, 4S)-3b. The structure and stereochemistry of each product was established by comparison with synthetic 3a and 3b by a combination of radio-TLC-phosphorimaging and LC-ESI(-)-MS-MS, as well as chiral capillary GC-MS analysis of the corresponding methyl esters 3a-Me and 3b-Me. The recombinant dehydratase domain from NANS module 2, NANS DH2, was shown to catalyze the formation of an (E)-double bond by syndehydration of the ACP-bound substrate anti-(2R,3R,4S,5R)-2,4-dimethyl-3,5-dihydroxyheptanoyl-ACP6 (4), generated in situ by incubation of (2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][AT6] didomain and ACP6 from DEBS module 6 along with the ketoreductase from the tylactone synthase module 1 (TYLS KR1). These results also indirectly establish the stereochemistry of the reactions catalyzed by the KR and enoylreductase (ER) domains of NANS module 2.

  DOI：

  10.1021/ja1073432

文献信息

• Carbon-13 NMR spectra of saturated heterocycles: XI—Tetrahydropyrans (oxanes)
  作者：Ernest L. Eliel、Muthiah Manoharan、K. Michal Pietrusiewicz、Karl D. Hargrave

  DOI：10.1002/omr.1270210205

  日期：1983.2

  AbstractThe 13C NMR spectra of 62 oxanes (tetrahydropyrans) with and without methyl substituents at various ring positions, some of them bearing in addition (or instead) ethyl, vinyl, ethynyl, carbomethoxy and methylol substituents at C‐2, have been recorded, and the 294 resulting chemical shifts have been correlated by multiple linear regression analysis. Axial and equatorial α‐, β‐, γ‐, δ‐, gem‐ and vic‐parameters for shifts caused by methyl groups at all ring positions, and similar parameters for Et,—CHCH2,—CCH, CO2Me and CH2OH groups at C‐2, are reported. Standard deviations of the parameters are, in most cases, within 0.3 ppm and the agreement of calculated and experimental shifts is excellent. This is probably the largest parameter set of this type extant. 13C NMR spectra of a number of additional substituted tetrahydropyrans, and of 3,6‐dihydro‐2H‐pyrans and 3,4‐dihydro‐2H‐pyrans, are tabulated and discussed.