两个天然查尔酮苷的全合成

以香草酮和对羟基苯甲醛为原料,经酚羟基保护、羟醛缩合、相转移催化法接糖、去保护基等反应合成了两个天然查尔酮苷——4’-O-β-D-喃葡萄基-3’-甲氧基-4-甲氧基-查尔酮和4’-O-β-D-喃葡萄基-3’-甲氧基-4-羟基-查尔酮,总收率分别为17.2%和20.8%,其结构经1H NMR,13C NMR和HR-MS确证。在脱保护基反应中,首次提出了NH4Cl脱除MOM保护基的新方法。     

(±)-Cycloaltilisin 7和(±)-Poinsettifolin B的首次全合成

Cycloaltilisin 7是从桑科植物面包树(Artocarpus altilis)的芽中分离出的一种新异戊烯基黄烷酮,具有组织蛋白酶K抑制活性;Poinsettifolin B也是从桑科琉桑属植物Dorstenia poinsettifolia中分离出的一种新的香叶基查尔酮,Dorstenia poinsettifolia是原产于喀麦隆潮湿森林的草本植物,用于民间雅司病和伤口感染的治疗,对治疗皮肤病也有潜在功效.以廉价的羟苯乙酮和羟苯甲醛为原料,用简单温和的方法完成了这两种天然产物的首次全合成.所有新化合物的结构都经过HRMS,1H NMR和13C NMR的确认.     

1,2-Dihydroparatocarpin A的全合成

以对羟基苯甲醛和2,4-二羟基苯乙酮为起始原料,经C-异戊烯基化、保护酚羟基、羟醛缩合、DDQ环化及对甲基苯磺酸催化环化等反应,首次完成了天然异戊烯基查尔酮衍生物1,2-Dihydroparatocarpin A的全合成,总收率21.8%。化合物的结构经1H NMR,IR和MS确认。     

天然产物Luxenchalcone的全合成

以对羟基苯甲醛和2,4-二羟基苯乙酮为起始原料,经过甲氧甲基化、溴代、Ullmann反应、羟醛缩合和脱保护等反应,完成了天然产物双查尔酮Luxenchalcone的全合成,关键步骤为Ullmann反应,重要中间体和目标产物的化学结构经 ¹H NMR,¹³C NMR和ESI-MS等表征确认.     

红景天苷的全合成

以对羟基苯甲醛为原料,经酚羟基保护、醛基还原、氯代、氰化、水解、酯化和还原反应制得关键中间体4-苄氧基苯乙醇(6);6与溴代四乙酰基葡萄糖偶联后脱保护基合成了红景天苷,总收率12.8%,其结构经1H NMR,13C NMR,IR和HR-MS确证。     

五个天然异戊烯基黄酮的首次全合成研究

完成了具有2,3-二羟基-3-甲基丁基黄酮化合物brosimacutin A-B,brosimacutin D,brosimacutin E,brosimacutin H和brosimacutin M五个黄酮类化合物的消旋体的合成.所有新化合物的结构都经过NMR,HRMS确认.     

2′,4-二羟基-4′,6′-二甲氧基-二氢查尔酮的首次全合成

以2,4,6-三羟基苯乙酮和对羟基苯甲醛为起始原料,经选择性的甲基化,甲氧甲基化,羟醛缩合,还原,脱保护等反应首次完成了2′,4-二羟基-4′,6′-二甲氧基-二氢查尔酮(1)的全合成,总收率40%。1和中间体的结构经1HNMR,IR和MS表征。     

(±)-Abyssinone Ⅰ的全合成

以对羟基苯甲醛和2,4-二羟基苯乙酮为起始原料,经过C-异戊烯基化、选择性的保护酚羟基、羟醛缩合、催化环化、去保护基等步骤,以25%的总收率首次完成了天然产物(±)-AbyssinoneⅠ(1)的全合成。其中新化合物4,7,8和1的结构经1H NMR,IR和MS表征。     

(±)-Diplacone与(±)-3'-O-methyldiplacone的全合成

以廉价的香草醛,3,4-二羟基苯甲醛和2,4,6-三羟基苯乙酮为初始原料,经过C-香叶基化、羟基保护、羟醛缩合、脱去保护基以及催化环化等步骤,以11%和20%的总收率实现了两个天然香叶基黄烷酮(±)-diplacone与(±)-3′-O-methyldiplaone的首次全合成,其结构经¹H NMR, IR和MS表征。     

加压毛细管电色谱测定葛根中三种异黄酮类化合物

建立了加压毛细管电色谱(pCEC)检测葛根中异黄酮类化合物葛根素、大豆苷、大豆苷元的方法。采用C18毛细管色谱柱,以NaH2PO4缓冲盐水溶液和甲醇为流动相,优化流动相比例、流动相流速、NaH2PO4缓冲盐水溶液浓度和pH、分离电压等色谱条件。结果表明,在流动相为17.5 mmol/L NaH2PO4缓冲盐水溶液(pH 4.0):甲醇=55:45(V/V),分离电压3 kV,流动相流速80μL/min,检测波长250 nm的条件下,葛根素、大豆苷、大豆苷元质量浓度在200～1000μg/mL范围内线性关系良好,相关系数在0.9960～0.9982之间,平均回收率在98.6%～100.9%之间,RSD为3.1%～3.5%之间。该方法已用于葛根中异黄酮类物质的分离检测。     

Total synthesis of an isoflavone C-glycoside: 6-tert-butylpuerarin

The first total synthesis of an isoflavone C-glycoside (6-tert-butylpuerarin) using commercially available 4,6-di-tert-butylbenzene-1,3-diol as starting material was achieved in five steps with an overall yield of 2.8%. The key intermediate 4 was obtained by de-tert-butylation of 2 with trifluoroacetic acid and Friedel-Crafts acetylation of 2-C-β-D-glucopyranoside 3. Condensation of 4 with 4-(benzyloxy)benzaldehyde resulted in the formation of C-glucosylchalcone 5, which was cyclized by oxidative rearrangement using (diacetoxyiodo)benzene (DIB) and p-toluenesulfonic acid to obtain the target molecule 6. This environmentally friendly and concise synthetic pathway should be applicable to the large-scale synthesis of various isoflavone C-glycosides.     

糖碳苷类化合物的合成方法研究进展

综述了近年来利用重排反应、W ittig反应、金属有机反应等方法合成糖碳苷类化合物的研究进展。参考文献30篇。     

Synthesis of a C-glycoside analogue of beta-D-galactosylthreonine

A C-linked analogue of beta-D-galactosylthreonine has been prepared from 2,3,4,6-tetra-O-benzyl-D-galactopyranolactone (1) in 14 steps. Three stereogenic centers were created during the synthesis, with the anomeric center of the C-glycoside being generated first by addition of a Grignard reagent to 1 and subsequent reduction of the intermediate hemiacetal with triethylsilane. The two stereogenic centers in the threonine moiety were both established by alkylation of Evans' chiral N-acyloxazolidinone enolates.     

Synthesis of double C-glycoside analogue of sTn

A sTn double C-glycoside, sTn analogue 2, was synthesized using samarium chemistry developed in our laboratory. Complications in the oxidation reaction affording aldehyde acceptor were overcome by double protection of amide and the use of a room-temperature ionic liquid as solvent. Studies are underway to conjugate the sTn double C-glycoside hapten 2 to KLH carrier protein for biological evaluation as a vaccine.     

Synthesis of a serine-based neuraminic acid C-glycoside

Cell-surface carbohydrates are classified by the nature of their linkages to the protein as either N-linked or O-linked. O- and N-glycans are involved in a number of important biological functions. These activities can be lost on glycoprotein catabolism when these glycan linkages are enzymatically hydrolyzed. The design and synthesis of novel C-linked glycans should provide catabolically stable glycoproteins useful for understanding and regulating important biological processes. Our efforts are currently directed toward the synthesis of C-glycosides of ulosonic acids. This paper describes the first synthesis of a serine-based neuraminic acid C-glycoside. The protecting group chemistry required for both carbohydrate and peptide syntheses complicates this approach. Different protecting group strategies were investigated for use in the samarium diiodide mediated C-glycosylation reaction. The key elements of our synthetic approach involve the following: (i) the substitution of homoserine for serine in the C-glycosylation reaction to introduce a carbon in place of the O-glycosidic oxygen, (ii) the use of benzyloxycarbonyl as a homoserine protecting group, compatible with samarium diiodide mediated C-glycosylation reaction, and (iii) the reduction of the carbonyl group in homoserine early in the synthesis to improve C-glycosylation yield and to avoid lactone formation. Using this combined approach, we prepared 4-O-acetyl-4-[2-C-(1-methyl 5-acetamido 4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-d-erythro-l-manno-nononate)]-2S-(benzyloxycarbonyl)amino-1-carboxylic acid (1), which will be used in peptide synthesis to prepare glycopeptides containing catabolically stable C-linked neuraminic acid.     

Total Synthesis of (-)-Maytansinol

A total synthesis of maytansinol (1) was achieved, in a convergent way, using (3S,6S,7S)-aldehyde 4 and (S)-p-tolyl sulfoxide 3 as fragments. When the anion of 3 was condensed with aldehyde 4, some induction at C(10) was observed (60% de), giving the C(1)-N(19)-open-chain compound 7, after thermal elimination of sulfinate. Pure E/E stereochemistry of the 11,13-diene was obtained. Selective modifications of the functionalities permitted macrocyclization and further elaboration to maytansinol.     

Total Synthesis of (±)-Zearalanone

Summary.  A new approach to the macrocyclic lactone zearalanone is described utilizing an alkenol and an arene trifluoromethanesulfonate as starting materials. The key step is a Pd(0)-catalyzed cross-coupling of the arene trifluoromethanesulfonate with a 9-alkyl-9-borabicyclo[3.3.1]nonane derived from the alkenol. The title compound is obtained by macrolactonization of a hydroxy acid under Mitsunobu conditions. Received December 29, 2000. Accepted February 5, 2001     

(±)-耳壳藻内酯的全合成研究(Ⅱ)

以2,6,6-三甲基环己-2-烯-1,4-二酮为原料, 经选择性羰基保护、Wittig反应、脱保护基、 腈基水解和还原等5步反应合成了目标化合物, 总产率可达6.0%.