维生素E的不对称合成

系统地综述了维生素E的合成方法, 旨在为进行维生素E及其相关萜类化合物合成的研究人员提供参考.     

Tocopherols and Triterpenoids from Sida acuta

A new tocopherol derivative, 7_a‐methoxy‐α‐tocopherol ( 1 ), and a new taraxastane triterpene, taraxast‐1,20(30)‐dien‐3‐one ( 5 ), together with four known compounds, β‐tocopherol ( 2 ), α‐tocopherol ( 3 ), α‐tocospiro B ( 4 ) and taraxasterone ( 6 ) were isolated from the whole plant of Sida acuta. Their structures were elucidated by spectral analysis including MS, 1D and 2D‐NMR spectroscopy. Among those compounds, compounds 1 , 2 , and 3 showed significant antioxidant effect (EC₅₀ = 86.9, 68.2, and 70.9 μM, respectively) in the DPPH radicals scavenging activity assay.     

Induced Production,Synthesis, and Immunomodulatory Action of Clostrisulfone,a Diarylsulfone from Clostridium acetobutylicum

The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum, the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra-physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone ( 1 ). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compound. Clostrisulfone is the first reported natural product with a diphenylsulfone scaffold. A biomimetic synthesis suggests that pentamethylchromanol-derived radicals capture sulfur dioxide to form 1 . In a cell-based assay using murine macrophages a biphasic and dose-dependent regulation of the LPS-induced release of nitric oxide was observed in the presence of 1 .     

Convenient Preparation of 2,7,8‐Trimethyl‐6‐hydroxychroman‐2‐carboxylic Acid (γ‐Trolox)

The title chroman is useful in synthesis and as a water‐soluble analog of γ‐tocopherol, a member of the vitamin E family. This new synthesis of γ‐trolox proceeds via selective aromatic demethylation of Trolox, the more easily available 2,5,7,8‐tetramethyl homolog compound. This route is shorter than the previous synthesis, avoids the use of cyanide and methoxybutadiene, and requires no chromatography.     

Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[¹⁸F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([¹⁸F]F-γ-T-3) was prepared for this purpose. [¹⁸F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [¹⁸F]fluoride in DMF/K₂₂₂. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [¹⁸F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [¹⁸F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [¹⁸F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.     

Doping Polysulfone Membrane with Alpha‐Tocopherol and Alpha‐Lipoic Acid for Suppressing Oxidative Stress Induced by Hemodialysis Treatment

The reduction of free radicals by bioactive membranes used for hemodialysis treatment is an important topic due to the constant rise of oxidative stress‐associated cardiovascular mortality by hemodialysis patients. Therefore, it is urgent to find an effective solution that helps to solve this problem. Polysulfone membranes enriched with α‐lipoic acid, α‐tocopherol, and with both components are fabricated by spin coating. The antioxidant properties of these membranes are evaluated in vitro by determining the lipid‐peroxidation level and the total antioxidant status of the blood plasma. The biocompatibility is assessed by quantifying the protein adsorption, platelet adhesion, complement activation, and hemolytic effect. All types of membranes show in vitro antioxidant activity and a trend to reduce oxidative stress in vivo; the best results show membranes prepared with a combination of both compounds and prove to be nonhemolytic and hemocompatible. Moreover, the membrane specific separation ability for the main waste products is not affected by antioxidants incorporation.     

Fatty acid composition and tocopherol profiles of safflower (Carthamus tinctorius L.) seed oils

The oil contents of safflower seeds ranged from 23.08% to 36.51%. The major fatty acid of safflower oil is linoleic acid, which accounted for 55.1–77.0% in oils, with a mean value of 70.66%. Three types of tocopherols were found in safflower oil in various amount α-tocopherol, β-tocopherol and γ-tocopherol, ranged from 46.05 to 70.93 mg/100 g, 0.85 to 2.16 mg/100 g and trace amount to 0.45 mg/100 g oils, respectively. This research shows that both fatty acid and tocopherol contents differ significantly among the safflowers.     

Rapid determination of lipophilic vitamins in human serum by ultra‐high performance liquid chromatography using a fluorinated column and high‐throughput miniaturized liquid–liquid extraction

A high‐throughput miniaturized liquid–liquid extraction procedure followed by a simple ultra‐high performance liquid chromatography method coupled with fluorescence detection for bioanalytical analysis of all tocopherol isomers and retinol in human serum has been developed and validated. In the extraction procedure, a synthetic internal standard tocol was used, which does not occur in the human body. The separation of structurally related vitamins was achieved using a new generation of pentafluorophenyl propyl core–shell stationary phase with elution using methanol and an aqueous solution of ammonium acetate. The fluorescence of retinol and tocopherol isomers was detected at λ_ex = 325, 295 nm and λ_em = 480, 325 nm, respectively. The rapid baseline separation of all analytes was accomplished within 4.0 min. The sensitivity of method was demonstrated with lower limits of quantification: retinol 0.01 μM, α‐tocopherol 0.38 μM, β‐tocopherol 0.18 μM, γ‐tocopherol 0.14 μM, and δ‐tocopherol 0.01 μM. Possible application of this method in clinical practice was confirmed by the analysis of human serum samples from healthy volunteers. Finally, the simultaneous determination of retinol and all tocopherol isomers in human serum can enable the clarification of their role in metabolism and in diseases such as cancer.     

Analysis of the Dynamic Decomposition of Unsaturated Fatty Acids and Tocopherols in Commercial Oils During Deep Frying

The decomposition of unsaturated fatty acids and tocopherols in 10 commercial edible oils during deep frying was investigated. The dominant tocopherol in oils rich in polyunsaturated fatty acids (PUFAs) was γ-tocopherol, except for natural perilla oil (δ-tocopherol dominant), and the main tocopherol in oleic acid-rich oils was α-tocopherol. The PUFA-rich oils had higher tocopherol contents than the oleic acid-rich oils. Both the reduction rate of total unsaturated fatty acid (TUFA) and total tocopherol (TToc) were linear with frying time (t). The decomposition rate of TToc is faster than that of TUFA since the slope values obtained from fitting equations (Y?=?k t) k_TToc (1.520–14.483) were obviously larger than for k_TUFA (0.155–0.270). By establishing a dynamic decomposition index, unsaturated fatty acids and tocopherol in oils showed dynamic decomposition over multiple frying cycles. The obtained results showed that decomposition characteristics of oils are related to their fatty acid compositions.     

高效液相色谱荧光检测法快速测定天然生育酚中痕量苯并[a]芘

建立了一种快速、新颖的高效液相色谱荧光检测法测定天然生育酚中痕量苯并[a]芘.天然生育酚样品经中性氧化铝柱色谱富集和净化后在 XDB-C,18反相柱上,采用水-乙腈(体积比20比80)为流动相进行分离,采用荧光检测器进行检测,其激发波长为 260 nm,发射波长为 408 nm.苯并[a]芘的定量下限为 0.50 ng·g-1.加标回收率大于 77.9%.分析了 3 个不同试样,测定结果的相对标准偏差在 3.0%～10.6%之间.