维生素D_2-A和CD片段醇的合成工艺改进

以维生素D_2(V-D_2)为原料,经高锰酸钾氧化、选择性切断和还原反应同时合成了维生素D_2-A(总产率30%)和CD片段醇(总产率45%),其结构经~1H NMR确证。     

工业固定床Fe-Cu-K催化剂浆态床F-T合成适应性研究

采用连续搅拌釜式反应器,在接近F-T合成实际工况下考察了工业固定床Fe-Cu-K催化剂浆态床F-T合成反应性能,研究反应温度、压力、原料气空速和氢碳摩尔比等操作参数对催化剂反应活性、产物选择性和稳定性的影响,实验总运转时间达2 500 h;同时采用扫描电镜技术（SEM）对催化剂的抗磨损性能进行了研究,结果表明,操作参数对催化剂的活性、选择性和目标产物产率有较大的影响,工业固定床Fe-Cu-K催化剂具有一定的抗磨损性能,F-T合成烃产物分布合理;催化剂具有较高的稳定性,在589 h的稳定条件运行内,催化剂的失活速率为0.23%/d（以CO转化率的降低计）;在整个运行期间CH4选择性维持在较低的水平。     

液相色谱-大气压化学电离串联质谱法测定婴幼儿配方奶粉中的维生素D

建立了婴幼儿配方奶粉中维生素D的液相色谱-大气压化学电离串联质谱(LC-APCI-MS/MS)分析方法。样品经正己烷和甲基叔丁基醚混合溶液提取,ProElut VDC固相萃取柱净化,Kinetex C_(18)色谱柱分离,采用大气压化学电离(APCI)源、正离子扫描和多反应监测(MRM)模式对维生素D_2和维生素D_3进行检测,内标法定量。结果表明维生素D_2和维生素D_3在5~5 000μg/L范围内均具有良好的线性关系,检出限为2μg/kg,定量限为5μg/kg。在5、10和100μg/kg添加水平下,维生素D_2和维生素D_3的回收率为85.2%~105.3%,相对标准偏差为4.7%~8.1%。该方法简便准确,灵敏度高,适用于婴幼儿奶粉中维生素D的测定。     

鼓泡浆态反应器中低温甲醇合成的探索

为了开发低温液相甲醇合成新工艺,使用CuCr／CH3ONa催化体系,在直径40mm的鼓泡浆液反应器中考察了低温甲醇合成的反应性能。鼓泡浆液反应器使用的浆液由铜铬催化剂、甲醇钠溶液、乳化剂OP-10和液相介质二甲苯组成。实验结果表明在90℃～110℃、4．8MPa和操作气速0．2cm／s下,前9h的CO平均转化率达到78％。甲醇是反应的主要产物。与搅拌釜中的实验结果比较,鼓泡浆液反应器的反应效率为搅拌釜的80％。这是由于甲醇钠的消耗和乳化剂的负效应所致。实验结果示范了鼓泡浆态反应器中低温甲醇合成的可行性。     

层柱稀土固体酸催化甲醇和环氧乙烷醚化反应

全面系统地考察了在层柱稀土固体酸催化剂上甲醇和环氧乙烷醚化反应.结果发现:层柱稀土固体酸催化剂具有较高的催化反应活性和较窄的分子量分布,对金属基本无腐蚀,具有环境友好特色;实验结果表明:间歇釜式反应器工艺生产乙二醇甲醚适宜操作条件是:醚化反应温度45～65 ℃,压力＜0.3 MPa,加料比甲醇∶环氧乙烷=1∶1(质量比).在此条件下,环氧乙烷转化率接近100%,甲醇转化率70.5%,乙二醇甲醚在产物中分布50%,产率70.2%,选择性70.1%,副产物(双醚)在产物中分布1.6%,确立了最佳工艺参数.     

维生素D_2类似物的合成及生物活性研究进展

1α,25-二羟基维生素D_2(1α,25-(OH)2-D_2,125D_2)是维生素D_2的活性代谢产物,1α,25-二羟基维生素D_3(125D)则是维生素D_3最具活性的代谢产物。125D因高钙血症副反应而限制其临床应用,而维生素D_2及其类似物一般比相应维生素D_3类化合物副作用小。本文综述了两种临床应用效果较好的维生素D_2类似物度骨化醇及帕立骨化醇的合成新进展,以及侧链修饰、19-去亚甲基、A环C_3位修饰和九重氢同位素标记的维生素D_2类似物的合成及生物活性研究新进展,旨在为新型活性维生素D_2类似物的合成及临床开发提供参考。     

Ni/Al2O3催化2-甲基呋喃加氢制2-甲基四氢呋喃性能的研究

采用浸渍法制备了不同NiO含量的Ni/Al₂O₃催化剂,并进行了2-甲基呋喃加氢制2-甲基四氢呋喃性能的考察。结果表明,在制备的NiO负载量为10%、20%、25%、30%和40%的Ni/Al₂O₃催化剂中,随着NiO负载量增加,加氢反应的选择性与2-甲基呋喃的转化率均呈现出先增加后减小的趋势。其原因是由于适当增加NiO负载量有利于催化剂表面活性中心的形成,有利于加氢反应的进行;但是过度负载的NiO容易堵塞Al₂O₃载体中的介孔通道,降低反应的转化率与选择性。在釜式反应器中进行反应,对加氢反应条件进行了优化,发现在反应压力为3 MPa、反应温度150℃、机械搅拌速率为1000 r/min时,Ni/Al₂O₃催化2-甲基呋喃加氢制2-甲基四氢呋喃具有较高的选择性。当NiO负载量为25%时,2-甲基四氢呋喃的选择性最高为97.1%,2-甲基呋喃的转化率达到99.4%。     

Ti-MOR钛硅分子筛催化甲乙酮氨氧化反应性能

以TiCl4蒸气处理深度脱铝的丝光沸石,采用气固相同晶置换制备了含钛丝光沸石(Ti-MOR),并以H2O2作为氧化剂,考察了釜式反应器中Ti-MOR催化甲乙酮(MEK)与氨的液相氨氧化反应合成甲乙酮肟(MEKO)的性能,进而在连续淤浆床反应器中评价了Ti-MOR的稳定性和选择性.结果表明,在优化的反应条件下,Ti-MOR催化剂上MEK连续氨氧化反应的转化率和MEKO选择性分别达到95%和99%以上,优于传统的钛硅分子筛TS-1;同时,MEK转化率、MEKO选择性、催化剂耐积炭性以及稳定性等指标接近结构重排改性的Ti-MWW催化剂.     

化学与生物转化法合成帕立骨化醇

以维生素D2(1)为原料,通过七步有机合成反应和一次生物转化,成功获得了帕立骨化醇9,并得到了一条新的合成帕立骨化醇的路线,收率为3.24%.该合成方法路线短,操作简便,收率较文献中的方法有较大提高.所有产物结构经1H NMR,13C NMR和MS表征.     

光-Fe3+-草酸体系中对氯苯酚的冰相光转化

本文利用室内低温反应装置研究了在模拟太阳光-Fe3+-草酸作用下冰相中对氯苯酚（4-CP）的光转化。结果表明,Fe3+-草酸存在条件对冰相中4-CP的光转化有促进作用。Fe3+和草酸初始浓度、Fe3+与草酸的初始浓度比以及初始pH值对体系中4-CP的转化率具有较大影响。当溶液初始pH值为6.50,Fe3+和草酸的初始浓度比是1/5,草酸初始浓度为0.80mmol/L时,4-CP光照7.5h转化率可达39.1%。在光转化过程中,TOC的转化率滞后于4-CP的光转化率。4-CP的光转化符合一级动力学模型。分别利用直接萃取法和衍生化法富集了反应中间产物,并采用GC-MS进行了分析,据此推断了冰相中模拟太阳光-Fe3+-草酸作用下4-CP光转化的反应机理。     

Determination of vitamin D3 and its isomers in D3 resins and in mixtures with vitamin A acetate (author's transl)]

Vitamin D3 and its isomers, prepared from 7-dehydrocholesterol by photochemical reaction, can be separated and quantitatively determined by high-pressure liquid chromatography on aluminium oxide using chloroform as the eluting agent. The determination of small amounts of vitamin D3 in an excess of vitamin A acetate can be achieved by the same method.     

UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in the human keratinocyte line HaCaT

We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol. The present study was initiated to test whether ultraviolet B (UVB)-induced photolysis of provitamin D3 (7-dehydrocholesterol, [7-DHC]) which results in the formation of vitamin D3 also leads to the generation of calcitriol in keratinocytes. Submerged monolayers of HaCaT keratinocytes were preincubated with 7-DHC (25 microM) at 37 degrees C and irradiated with monochromatic UVB at different wavelengths (effective UV-doses: 7.5-60 mJ/cm2), or a narrow-band fluorescent lamp Philips TL-01 (UVB-doses: 125-1500 mJ/cm2). Irradiation with both sources of UVB resulted in the generation of different amounts of previtamin D3 in our in vitro model followed by time-dependent isomerization to vitamin D3 and consecutive formation of calcitriol in the picomolar range. Unirradiated cultures or cultures exposed to wavelengths > 315 nm generated no or only trace amounts of calcitriol. The conversion of vitamin D3 generated after UVB irradiation to calcitriol is inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases in this chemical reaction. The generation of calcitriol was wavelength- and UVB dose dependent and reached approximately 18-fold higher levels after irradiation at 297 nm than at 310 nm (effective UVB dose: 30 mJ/cm2). Hence, keratinocytes may be a potential source of biologically active calcitriol within epidermis, when irradiated with therapeutical doses of UVB.     

The vitamin D3 pathway in human skin and its role for regulation of biological processes

The skin is the only tissue yet known in which the complete ultraviolet-B (UV-B)-induced pathway from 7-dehydrocholesterol to hormonally active calcitriol (1alpha,25-dihydroxyvitamin D(3)) occurs under physiological conditions. Epidermal synthesis of calcitriol could be of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their antiproliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. The known antipsoriatic effect of UV-B light could, at least in part, be mediated via UV-B-induced synthesis of calcitriol. In addition, mounting evidence indicates that cutaneous vitamin D(3) synthesis is of high importance for the prevention of a broad variety of diseases, including various malignancies. New but controversially discussed sun-protection guidelines were established for the prevention of internal cancers. A better understanding of the metabolism of vitamin D in the skin opens new perspectives for therapeutic applications of vitamin D analogs.     

An LC-MS/MS Method for Analysis of Vitamin D Metabolites and C3 Epimers in Mice Serum: Oral Supplementation Compared to UV Irradiation

Introduction: The most common forms of vitamin D in human and mouse serum are vitamin D3 and vitamin D2 and their metabolites. The aim of this study is to determine whether diet and sunlight directly affect the circulating concentrations of vitamin D metabolites in a mouse model. We investigated the serum concentrations of eight vitamin D metabolites—vitamin D (vitamin D3 + vitamin D2), 25OHD (25OHD3 + 25OHD2), 1α25(OH)₂D (1α25(OH)₂D2, and 1α25(OH)₂D3)—including their epimer, 3-epi-25OHD (3-epi-25OHD3 and 3-epi-25OHD2), and a bile acid precursor 7alpha-hydroxy-4-cholesten-3-one (7αC4), which is known to cause interference in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Method: The LC-MS/MS method was validated according to FDA-US guidelines. The validated method was used for the analysis of mouse serum samples. Forty blood samples from mice were collected and divided into three groups. The first group, the DDD mice, were fed a vitamin D-deficient diet (25 IU VD3/kg of diet) and kept in the dark; the second group, the SDD mice, were maintained on a standard-vitamin D diet (1000 IU VD3) and kept in the dark; and the third group, SDL, were fed a standard-vitamin D diet (1000 IU VD3) but kept on a normal light/dark cycle. LC-MS/MS was used for the efficient separation and quantitation of all the analytes. Results: The validated method showed good linearity and specificity. The intraday and interday precision were both <16%, and the accuracy across the assay range was within 100 ± 15%. The recoveries ranged between 75 and 95%. The stability results showed that vitamin D metabolites are not very stable when exposed to continuous freeze–thaw cycles; the variations in concentrations of vitamin D metabolites ranged between 15 and 60%. The overlapping peaks of vitamin D, its epimers, and its isobar (7αC4) were resolved using chromatographic separation. There were significant differences in the concentrations of all metabolites of vitamin D between the DDD and SDL mice. Between the groups SDD (control) and SDL, a significant difference in the concentrations of 3-epi-25OHD was noted, where C3 epimer was about 30% higher in SDL group while no significant differences were noted in the concentrations of vitamin D, 25OHD, 1α25(OH)₂D, and 7αC4 between SDD and SDL group. Conclusions: A validated method, combined with a simple extraction technique, for the sensitive LC-MS/MS determination of vitamin D metabolites is described here. The method can eliminate the interferences in LC-MS/MS analysis caused by the overlapping epimer and isobar due to them having the same molecular weights as 25OHD. The validated method was applied to mouse serum samples. It was concluded that a standard-vitamin D diet causes an increase in the proportion of all the vitamin D metabolites and C3 epimers and isobar, while UV light has no pronounced effect on the concentrations of the majority of the vitamin D metabolites except 3-epi-25OHD. Further studies are required to confirm this observation in humans and to investigate the biochemical pathways related to vitamin D’s metabolites and their epimers.     

Ultrafast electrocyclic ring opening in previtamin D photochemistry

Photochemical reactions of 7-dehydrocholesterol and lumisterol were studied by nanosecond and picosecond UV laser excitation. The resulting production of previtamin D and tachyslerol was analysed by chromatography. With picosecond excitation, the formation of the secondary product tachysterol was significantly reduced. Model calculations gave reactive and non-reactive rate constants for 7-dehydrocholesterol and lumisterol.     

Effect of Reaction Media on Photoreaction of Provitamin D_3

IntroductionThe photochemistry of provitamin D3 (Pro) has been studied extensively in many years1-4. As shown in Scheme 11, irradiation of provitamin D3 in organic solvents results in its photoisomerization to previtamin D3 (Pre). Previtamin D3 can be thermally transferred into vitamin D3 (VD3), which is of commercial interests. However, previtamin D3 also undergoes the photochemical back reaction leading to the regeneration of provitamin D3 and the photoisomerization resulting in the und…     

In vitro model of vitamin D3 (cholecalciferol) synthesis by UV radiation: dose-response relationships

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.     

超薄Ni(OH)2纳米片修饰Zn0.5Cd0.5S纳米颗粒作为二维/零维异质结构光催化剂可见光下光催化制氢

设计与制备高效的光解水催化剂是解决能源问题和环境问题的策略之一.硫化镉因其可在可见光引发下分解水制氢而受到广泛关注,然而光腐蚀严重,过电势高,载流子复合快速以及表面反应动力学缓慢等缺点极大地限制了其在光解水反应中的实际应用.本文采用简单液相法将均匀的Zn0.5Cd0.5S纳米颗粒锚定在超薄Ni(OH)2纳米薄片上,构建...     

New methodology for the synthesis of 25-hydroxyvitamin D conjugates

A new method for synthesizing regiospecific 3-position vitamin D conjugates is described. Reaction of either 25-dihydroxyvitamin D2 or 25-dihydroxyvitamin D3 with p-nitrophenylchloroformate resulted in conversion to the respective 3-p-nitrophenylcarbonates. Reaction of the p-nitrophenylcarbonates with amines produced the 3-carbamates in good yield. Careful selection of commercially available amines and non-acidic conditions made this pathway amenable to the preparation of fluorescent, chemiluminescent, or biotinylated conjugates. This strategy offers a general method for the preparation of vitamin D conjugates.     

THF: An Efficient Electron Donor in Continuous Flow Radical Cyclization Photocatalyzed by Graphitic Carbon Nitride

Mesoporous graphitic carbon nitride (mpg‐C₃N₄) was found to be an efficient heterogeneous photocatalyst for the metal‐free radical cyclization of 2‐bromo‐1,3‐dicarbonyl compounds. Reactions leading to functionalized cyclopentanes proceed under mild conditions and can be conducted in a continuous flow photoreactor. Compared to the batch reaction, the use of a continuous flow reactor resulted in a significant reduction in reaction time (complete conversion of 0.04 mmol of substrate in a batch was achieved after 4 h, whereas in a flow reactor the same amount of substrate was fully converted into a product within 40 min). Mechanistic studies of the reaction showed that THF plays not only the role of solvent, but is also a crucial hydrogen and electron donor.