维生素D衍生物的临床应用及合成方法

维生素D及其衍生物不仅可以作为治疗疾病的药物,而且也可以成为化学合成的原料。现在有些维生素D及其衍生物已经作为商品投放在市场上,并对临床研究和工业合成做出了巨大的贡献。对目前临床做出贡献的维生素D衍生物马沙骨化醇、度骨化醇、帕立骨化醇、骨化三醇、卡泊三醇和他卡西醇在临床方面的应用及合成路线进行了介绍,对药物的开发提供参考,并进一步提出未来药物开发的前景。     

维生素A醛的合成研究

研究维生素A醛的合成方法。以维生素A醇为原料,经过烯丙位氧化制得维生素A醛。通过对科林试剂及其衍生物、活性MnO2作为维生素A醇的烯丙位氧化剂进行研究,确定了活性MnO2作为制备维生素A醛的氧化剂。通过对活性MnO2制备方法的研究,开发了晶型为G型的活性MnO2。G型的活性MnO2用于维生素A醛的制备中,其氧化活性高,选择性好,制备的维生素A醛粗品含量达到80%以上,氧化收率达70%以上。产品通过精制,含量可达95%以上,精制收率达94%以上。     

维生素C衍生物的制备及其在化妆品中的应用

维生素C衍牛物克服了维生素C易被氧化不稳定的缺点,被广泛用于化妆品中.阐述了维生素C衍生物围内外的研究情况,主要对维生素C的磷酸酯盐、糖苷、棕榈酸酯、乙基醚、甲基硅基等衍生物的制备方法进行了总结.介绍了其在化妆品中的应用情况,指出了维生素C衍生物的发展趋势.     

胆固醇制备7-脱氢胆固醇的研究进展

7-脱氢胆固醇作为制备维生素D_3及其衍生物的关键中间体,主要通过胆固醇烯丙位取代消除反应来合成。综述了7-脱氢胆固醇几种代表性的合成方法,并对合成方法进行了分析总结。     

氯气有机衍生产品(连载四) 第四章 丙烯系列衍生物

丙烯系列衍生物由:丙烯的S.D氯化反应产物、丙烯的次氯酸化反应产物、丙烯聚合物的氯衍生物、丙烯的高温氯化反应产物等四组组成。第一节丙烯的S.D氯化反应产物丙烯的S.D.氯化反应产物如前所述有四氯乙烯和四氯化碳二种。这一部分将在第五章第二节详细介绍,这里不再多述。     

维生素C磷酸酯衍生物的制备及其在化妆品中的应用

维生素C磷酸酯克服了维生素C易被氧化的缺点并且在化妆品中应用广泛。本文阐述了国内外研究现状,总结了化学合成和生物发酵制备维生素C磷酸酯衍生物的方法,介绍了它们在化妆品中的应用情况。指出中国应加快研发维生素C磷酸酯衍生物及其它衍生物。     

“一锅法”合成(E)-1,4-二羰基丁-2-烯酯衍生物

以邻二醇和乙氧甲酰基亚甲基三苯基膦为原料,二氯甲烷为溶剂,MnO2存在下,加热至45℃,通过串联伯醇氧化反应,Witting反应和烯丙位羟基氧化反应的"一锅法"合成了(E)-1,4-二羰基丁-2-烯酯衍生物。共合成了7个目标产物,且都通过核磁共振谱和质谱对其结构进行了确证。     

维生素K_2(35)关键中间体的合成研究

以2-溴-1,4-二甲氧基-3-甲基萘和溴代香叶醇为起始原料,经偶联反应和烯丙位末端氧化反应得到维生素K_2(35)关键中间体,总收率为64.9%,其结构经MS、~1H NMR、13C NMR确证。     

丙烯氢氧环氧化动力学与反应器概念设计研究进展

环氧丙烷（PO）在全球产能最高的35种化学品中,是仅次于聚丙烯的第二大丙烯衍生物,主要用于生产聚醚多元醇、聚氨酯等。相比传统的氯醇法、共氧化法和双氧水直接氧化法（HPPO）等PO生产工艺,丙烯在氢氧混合气中一步环氧化制PO（HOPO）具有工艺简单、选择性高、产物易分离、能耗低等突出优势,是生产PO的理想工艺。重点介绍了丙烯氢氧环氧化反应动力学研究进展,包括主、副反应动力学模型以及催化剂失活模型。总结了基于该过程安全操作的反应器概念设计进展。分析了丙烯氢氧环氧化反应存在的挑战,从副产物生成途径、失活动力学及颗粒催化剂上的动力学等方面展望了可能的研究方向。     

维生素D衍生物的合成及烯丙位氧化的优化

以维生素D2为原料,经过二氧化硫异构化、叔丁基二甲基氯硅烷进行羟基保护、碳酸氢钠/乙醇脱去二氧化硫、烯丙位氧化最终合成维生素D2衍生物5-(叔丁基-二甲基-硅烷氧基)-2-亚甲基-3-{2-[7a-甲基-1-(1,4,5-三甲基-己-2-烯基)-八氢-茚-4-亚基]-亚乙基}-环己醇,并改进后处理方法使反应前后产物较为稳定。考察反应温度、氧化剂和助氧化剂的用量、溶剂种类和体积配比、不同助氧化剂下的不同反应时间对烯丙位氧化产率的影响。结果表明,最佳反应条件为V(二氯甲烷)∶V(甲醇)∶V(1,2-二氯乙烷)=2∶1∶1,温度为50℃,n(底物)∶n(二氧化硒)∶n(助氧化剂)=1∶1∶4且N-甲基吗啉-N-氧化物为助氧化剂,此时烯丙位氧化的产率达65.1%,4步反应总收率为60.5%。     

Preparation of phosphorus esters of long-chain hydroxy fatty acids

Several procedures are evaluated for synthesis of phosphorus-containing derivatives of some long-chain hydroxy-fatty acids, including ricinoleic and lesquerolic acid and their hydrogenated products. The conventional method of preparing phosphate esters by reaction of an alcohol with a dialkyl phosphorochloridate is unsatisfactory, but introduction of the dialkyl phosphoryl group was accomplished by using dimethylformamide as catalyst. Phosphorus derivatives are obtained more conveniently by ester interchange between a long-chain hydroxy compound and a low molecular weight dialkyl phosphite. Purification of the phosphite esters was accomplished by partitoning between acetonitrile and petroleum ether and also by chromatography on a column of silicic acid. Attempts to prepare phosphorus derivatives of the allylic hydroxyl of methyl dimorphecolate resulted in extensive dehydration to the conjugated triene. Presented at the AOCS meeting in Toronto, Canada, 1962. A laboratory of the W. Utiliz. Res. & Dev. Div., ARS, U.S.D.A.     

Synthesis,characterizations and catalytic allylic oxidation of limonene to carvone of cobalt doped mesoporous silica templated by reed leaves

Reeds (Phragmites communis) leaves were successfully used as template in synthesis of cobalt doped mesoporous silica (Co/SiO₂/PC). The catalyst exhibited very high substrate conversion (100%) and relatively good product (carvone) selectivity (40.2%) for allylic oxidation of limonene to carvone using air as oxidant and acetic anhydride as solvent without adding any initiator. Fast hot catalyst filtration experiment proved that the catalyst acted as a heterogeneous one and it can be recycled easily and reused two times without significant loss of activity and selectivity.     

3，3-二乙氧基丙腈

3,3-二乙氧基丙腈是合成维生素B1、胞嘧啶及其衍生物等重要化合物的前体。综述了3,3-二乙氧基丙腈的合成方法,包括酰胺脱水、金属氰化物取代、醚化和异噁唑法,用于工业化生产较为满意的合成路线是以1,1,3,3-四乙氧基丙烷为原料的异噁唑法。     

Tandem reactions for streamlining synthesis: enantio- and diastereoselective one-pot generation of functionalized epoxy alcohols

[Reaction: see text] In 1980, Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki asymmetric epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981, Sharpless and co-workers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the synthesis of skeletally diverse epoxy alcohols.     

Oxidation of alcohols mediated by a polymer supported potassium ferrate as an effective mild oxidant

The use of polymeric oxidizing agents simplifies routine oxidation of reactions because it eliminates the traditional purification. In this article, the use of the cross‐linked poly (4‐vinylpyridine)‐supported potassium ferrate as an effective mild polymeric oxidizing agent is described. This reagent is capable of oxidizing organic compounds and can be used as a versatile reagent in organic synthesis. Primary and secondary benzylic and allylic alcohols are converted selectively to their carbonyl compounds, and hydroquinone to the 1, 4‐benzoquinone. This polymeric reagent seems to be nontoxic and nonpollutant. Based on our observation during the study, the polymeric reagent is stable and can be stored for months without losing its activity. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Selective oxidation of steroidal allylic alcohols using pyrazole and pyridinium chlorochoromate

Abastract This paper presents a modified method for the selective oxidation of allylic alchols. Pyrazole, when used with pyridinium chlorochromate, is a mild and useful reagent system for the rapid and selective oxidation of steroidal allylic alcohols to the corresponding α, β-unsaturated ketones. The reaction of each substrate was carried out by adding the oxidant to a dry methylene chloride solution containing pyrazole and an allylic alchol. This report is the first on the use of pyrazole to augment selective oxidation by a chronium (VI) reagent.     

Determination of the fatty acid profile by 1H‐NMR spectroscopy

The common unsaturated fatty acids present in many vegetable oils (oleic, linoleic and linolenic acids) can be quantitated by ¹H‐nuclear magnetic resonance spectroscopy (¹H‐NMR). A key feature is that the signals of the terminal methyl group of linolenic acid are shifted downfield from the corresponding signals in the other fatty acids, permitting their separate integration and quantitation of linolenic acid. Then, using the integration values of the signals of the allylic and bis‐allylic protons, oleic and linoleic acids can be quantitated. The procedure was verified for mixtures of triacylglycerols (vegetable oils) and methyl esters of oleic, linoleic and linolenic acids as well as palmitic and stearic acids. Generally, the NMR (400 MHz) results were in good agreement with gas chromatographic (GC) analyses. As the present ¹H‐NMR‐based procedure can be applied to neat vegetable oils, the preparation of derivatives for GC would be unnecessary. The present method is extended to quantitating saturated (palmitic and stearic) acids, although in this case the results deviate more strongly from actual values and GC analyses. Alternatives to the iodine value (allylic position equivalents and bis‐allylic position equivalents) can be derived directly from the integration values of the allylic and bis‐allylic protons.     

Synthetic strategies of marine polycyclic ethers via intramolecular allylations: linear and convergent approaches

Strategies for the synthesis of polycyclic ethers based on intramolecular allylations are overviewed. The intramolecular condensation of allylic stannanes and aldehydes is a powerful tool for the synthesis of oxepane derivatives. The reaction is successfully applied to the iterative total synthesis of hemibrevetoxin B (2). Further, the intramolecular allylation of alpha-acetoxy ethers provides an efficient method for the convergent synthesis of polycyclic ethers. The usefulness of the latter strategy is demonstrated in the convergent total synthesis of gambierol (4).