碳苷研究 XXVII. 黑豆素非环类似物的合成

本文报道天然黄酮碳苷黑豆素非环类似物的合成, 以2,4-二羟基苯乙酮为原料, 经酚羟基的单苄基化、Claisen重排、醇醛缩合、I2/DMSO/浓度H2SO4关环五步反应得到黄酮; 用Claisen重排, 分别在黄酮环生成之前和生成之后引入8-位取代基侧链, 收率国产高。修饰8-位烯丙基侧链, 得到了六个黑豆素类似物, 共中8的7-位为游离羟基。     

碳苷研究——ⅩⅩⅤⅡ.黑豆素非环类似物的合成

本文报道天然黄酮碳苷黑豆素非环类似物的合成.以2,4-二羟基苯乙酮为原料,经酚羟基的单苄基化、Claisen重排、醇醛缩合、I_2/DMSO/浓H_2SO_4关环五步反应得到黄酮;用Claisen重排,分别在黄酮环生成之前和生成之后引入8-位取代基侧链,收率较高.修饰8-位烯丙基侧链,得到了六个黑豆素类似物,其中8的7-位为游离羟基.     

碳苷研究XXVI:异黑豆素类似物的合成

本文首次报道了异黑豆素类似物, 6-非环糖基-4',7一二羟基黄酮的合成, 以2,4-二羟基苯甲酸为原料, 溴化和脱羧后以苄基作为羟基保护基, 通过Grignarcl反应获得具有各种不同侧链的中间体7,7氢解脱除苄基再用Fries重排或Frieclel-Crafts反应得到了C-Z酰化产物, 接着用碱缩合生成查尔酮, 经I2/H2SO4/DM SO氧化环合得到目标产物。     

碳苷研究XXVI:异黑豆素类似物的合成

本文首次报道了异黑豆素类似物, 6-非环糖基-4',7一二羟基黄酮的合成, 以2,4-二羟基苯甲酸为原料, 溴化和脱羧后以苄基作为羟基保护基, 通过Grignarcl反应获得具有各种不同侧链的中间体7,7氢解脱除苄基再用Fries重排或Frieclel-Crafts反应得到了C-Z酰化产物, 接着用碱缩合生成查尔酮, 经I2/H2SO4/DM SO氧化环合得到目标产物。     

碳苷研究——ⅩⅩⅥ.异黑豆素类似物的合成

本文首次报道了异黑豆素类似物,6-非环糖基-4′,7-二羟基黄酮的合成。以2,4-二羟基苯甲酸为原料,溴化和脱羧后以苄基作为羟基保护基,通过Grignard反应获得具有各种不同侧链的中间体7,7氢解脱除苄基再用Fries重排或Friedel-Crafts反应得到了C-乙酰化产物,接着用碱缩合生成查尔酮,经I_2/H_2SO_4/DMSO氧化环合得到目标产物1、2、3。     

萜品油烯的DeMayo光环加成产物的反应研究

通过萜品油烯和2，6-二氧代戊酸甲酯的de Mayo反应，使[2 + 2]环加成产物 3-6经retro-aldol重排，开环生成取代环己烯7和12。在不同反应介质中对开环产 物进行再环合，并对其反应机理进行研究。在碱性条件下，经分子内Claisen缩合 反应形成螺环化合物；以对甲本碘酸为催化剂的环合，除生成正常的Claisen缩合 产物以外，7和12均发生烯键亲核加成反应，生成具有二环[3.3.1]结构的桥环化合 物9-11和二环[3.2.1]结构的桥环化合物16-18。所得新化合物的化学结构均经IR, ~1H NMR，~(13)C NMR及元素分析予以确定。     

8-异戊烯基黄酮类天然产物的微波促进Claisen重排合成

8-异戊烯基黄酮是一类具有显著生物活性的天然产物.以2,4,6-三羟基苯乙酮和3,4-二羟基苯甲醛为原料,用氯甲基甲醚保护羟基,经羟醛缩合、碘催化环合、过氧丙酮(DMDO)氧化、O-异戊烯基化、微波促进的Claisen重排、脱甲氧甲基保护基、O-甲基化和异戊烯基侧链环合等反应步骤,完成了8-异戊烯基槲皮素-3-甲醚(1)、8-异戊烯基槲皮素-3,7,3',4'-四甲醚(2)和ArtochaminC(3)这3种8-异戊烯基黄酮类天然产物的合成.并对由微波促进的由5-O-异戊烯基黄酮类化合物合成8-C-异戊烯基黄酮类化合物的Claisen重排反应的关键步骤进行了探讨.所有合成的化合物经~1H NMR、~(13)C NMR和MS等结构确证.     

活性维生素D3类似物的合成及构效关系研究

1α,25-二羟基维生素D₃(1α,25-(OH)₂-D₃,125D)是维生素D中最具生理活性的代谢产物,但因高钙血症副反应而限制其临床应用。从对构效关系的研究出发,迄今已合成三千多种类似物。本文综述了近年来对某些A环修饰(C2位修饰、C3位修饰、芳香A环类似物、A环开环类似物)、侧链修饰、CD环修饰、seco-B环修饰和非开环甾体的活性维生素 D₃ 类似物的设计、合成以及构效关系的研究,旨在为新型较佳活性维生素D₃类似物的合成及临床开发提供参考。     

黄酮化合物的合成——推荐一个大学有机化学实验

以苯酚为原料,采用Baker-Venkataraman重排法合成黄酮化合物2-苯基苯并吡喃酮。实验内容包括成酯反应、Fries重排、Claisen缩合,实验操作包括水蒸气蒸馏、减压蒸馏、重结晶、熔点测定、薄层色谱、红外光谱和核磁共振图谱的解析等。该实验合成路线成熟,产物收率高,产品易于纯化。     

抗肿瘤天然产物汉黄芩素的合成

汉黄芩素(wogonin,5,7-二羟基-8-甲氧基黄酮)是传统中草药黄芩的有效成分之一,其抗肿瘤活性显著,且对肿瘤细胞的杀伤作用有其独特的机制.目前报道的化学合成法大多总收率较低,反应条件苛刻或原料来源困难.笔者以2,4-二苄氧基-6-羟基苯乙酮与苯甲醛为原料,经Claisen-Schmidt缩合、氧化关环得到5,7-二苄氧基黄酮,通过对5,7-二苄氧基黄酮的8-位碘代、硼酸酯化和氧化从而高效引入8-位羟基,再经甲基化和脱苄基保护完成汉黄芩素的克级合成,总收率大于70%,且反应条件温和、无需柱层析,适合规模化生产.为该类化合物的进一步结构修饰、活性和机制研究提供了保障.     

Stereospecific synthesis of dinosterol

Using a Claisen ortho-ester rearrangement, the biogenetically important marine sterol dinosterol and its C-24 epimer were synthesized stereospecifically by a sequence which is also attractive for selective isotope labelling in the side chain.     

Stereoselective total synthesis of cananginones (D–I) using Ireland–Claisen rearrangement as a key step

A strategy for stereoselective total synthesis of α-substituted γ-hydroxymethyl γ-butyrolactone containing bioactive natural products cananginones (D–I) has been developed using cheap and commercially available d-mannitol as a chiral pool. The Ireland–Claisen rearrangement is utilized as a key step to generate the α-substituted chiral center of the core lactone moiety, while the elongation of aliphatic side chain by different C-8 hydrocarbon groups have been achieved by alkylation, Cadiot–Chodkiewicz, and Sonogashira reactions.     

Ester-enolate Claisen rearrangement of proline-containing α-acyloxy-α-vinylsilane. Synthesis of pyrrolidine-fused glutamate analogs

The stereoselective syntheses of pyrrolidine-fused aspartate and glutamate analogs, (S)-α-carboxymethyl-proline 3 and (S)-α-2-carboxyethyl-proline 4, using a chirality-transferring ester-enolate Claisen rearrangement of α-vinyl-α-acyloxysilane having a Boc-Pro as an acyloxy group, are described. The stereochemical outcome of the proline ester-derived ester-enolate Claisen rearrangement is also disclosed.     

Experimental and computational investigation of the uncatalyzed rearrangement and elimination reactions of isochorismate

The versatile biosynthetic intermediate isochorismate decomposes in aqueous buffer by two competitive pathways, one leading to isoprephenate by a facile Claisen rearrangement and the other to salicylate via elimination of the enolpyruvyl side chain. Computation suggests that both processes are concerted but asynchronous pericyclic reactions, with considerable C-O cleavage in the transition state but relatively little C-C bond formation (rearrangement) or hydrogen atom transfer to the enolpyruvyl side chain (elimination). Kinetic experiments show that rearrangement is roughly 8-times more favorable than elimination. Moreover, transfer of the C2 hydrogen atom to C9 was verified by monitoring the decomposition of [2-(2)H]isochorismate, which was prepared chemoenzymatically from labeled shikimate, by (2)H NMR spectroscopy and observing the appearance of [3-(2)H]pyruvate. Finally, the isotope effects obtained with the C2 deuterated substrate are in good agreement with calculations assuming pericyclic reaction mechanisms. These results provide a benchmark for mechanistic investigations of isochorismate mutase and isochorismate pyruvate lyase, the enzymes that respectively catalyze the rearrangement and elimination reactions in plants and bacteria.     

General strategy for the synthesis of B1 phytoprostanes, dinor isoprostanes, and analogs

The synthesis of the phytoprostane B1 types I and II is achieved in high overall yield (35-53%) by only two principal transformations starting from 1,3-cyclopentanedione. The first side chain is attached via O-acylation of the 1,3-dione followed by rearrangement and reduction to give the 2-alkyl-1,3-diones 4a-c. After conversion into the corresponding vinylic iodides 5a-c, the second side chain is introduced by transition metal catalysis following Heck- or Sonogashira-type protocols. The whole spectrum of the phytoprostane B1 types I, II, and the dinor isoprostane B1 type III and some structural analogs are rapidly accessible along the same general protocol.     

Total syntheses of Nigrasin I and Kuwanon C

The efficient total syntheses of Nigrasin I and Kuwanon C, two biologically interesting natural flavonoids with two regioisomeric isoprenyl side chains, were realized for the first time starting from commercially available 1-(2,4,6-trihydroxyphenyl)ethanone via a linear reaction sequence of 11 steps with the overall yields of 22% and 21%, respectively, in which the selection of protective groups and the Claisen rearrangement of the allylated 16 featured the synthetic strategy. The use of acetic anhydride as the solvent and the employment of microwave irradiation are disclosed to be critically important in the efficient and selective Claisen rearrangement.     

Synthesis of 3-epi-6,7-dideoxyxestobergsterol A

3-Epi-6,7-dideoxyxestobergsterol A (2), an analogue of xestobergsterol A, has been synthesized from dehydroepiandrosterone (3) in 15 steps. The key synthetic intermediate, 15beta,16alpha-dioxypregn-17(20)E-ene derivative 8, was prepared from the corresponding 15beta,16beta-epoxide 6 by treating with acetic acid and titanium tetraisopropoxide. The 23-oxo side chain was constructed stereoselectively by orthoester Claisen rearrangement of 8 followed by introduction of an isobutyl group. Basic treatment of the 15,23-diketone 12 followed by deprotection gave the title compound 2.     

The Meyer-Schuster rearrangement: a new synthetic strategy leading to prostaglandins and their drug analogs, Bimatoprost and Latanoprost

Gold(I) mediated Meyer-Schuster rearrangement for the installation of the ‘lower’ side chain of prostaglandins and their analogs has been developed. This Au-mediated rearrangement, featuring a low catalyst loading and mild reaction conditions, has been demonstrated to be an efficient alternative to the standard Horner-Wadsworth-Emmons reaction in prostaglandin chemistry. Moreover, the present results provide a new synthetic process leading to pharmacologically active prostanoids: Latanoprost and Bimatoprost, that continue to hold key positions in the anti-glaucoma drug market.     

Microwave-mediated Claisen rearrangement followed by phenol oxidation: a simple route to naturally occurring 1,4-benzoquinones. The first syntheses of verapliquinones A and B and panicein A

The naturally occurring 1,4-benzoquinones 2-methoxy-6-propyl-1,4-benzoquinone (1), 2-methoxy-6-pentyl-1,4-benzoquinone (primin 2), 2-methoxy-6-pentadecyl-1,4-benzoquinone (3), 2-methoxy-6-heptadecyl-1,4-benzoquinone (dihydroirisquinone, pallasone B; 4) were synthesized by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 10, followed by hydrogenation of the side chain alkene, and oxidation to the quinone. The Claisen-based methodology was extended to the first synthesis of the marine benzoquinones verapliquinones A and B (5 and 6), and panicein A (7). Isoarnebifuranone (9) was also synthesized by a similar strategy.     

De novo synthesis of teleocidin B analogs

Teleocidin B analogs have been synthesized in 24 steps and 1.9% overall yield. The key steps include aromatic Claisen rearrangement, intramolecular Heck reaction of a tetra-substituted alkene, and ruthenium (II) catalyzed indole cyclization. Teleocidin and the new analogs promote cell spreading on fibroblast cells that were treated with amino-Nogo, an inhibitor of cell spreading.