三尖杉碱全合成研究的新进展

三尖杉碱是抗癌药物-三尖杉酯类尖化合物的母体。它的全合成研究一直受到众多学者的亲睐。近几年来，取得了三条新的合成路线。共同特点是:采用单环或二环小分子为原料，巧妙地合成了具有独特五环结构的三尖杉硷(1)。其中的Kuehne路线，产率达到41%。     

全合成三尖杉碱的研究近况

三尖杉碱具有五元稠环结构，围绕着五环组建的先后顺序不同，产生各种拼合策略和设计。本文简要介绍近几年全合成三尖杉碱的新路线。参考文献１９篇。     

盐酸黄连碱的全合成

以2,3-二甲氧基苯甲醛为起始原料,经脱甲基、环和、缩和闭环等5步反应合成了盐酸黄连碱,总收率9.9%,其结构经1H NMR和MS表征.     

白屈菜红碱的全合成

以2,3-二甲氧基-6-溴苄醇(1)为起始原料,经过6步反应合成关键中间体2,3-二甲氧基-6-碘苯甲酸甲酯(7),通过金属钯催化下与中间体(8)的串联反应策略一步构筑了白屈菜红碱的B/C环,并以10步60.9%的总收率完成了白屈菜红碱的全合成,同时对关键的金属钯催化串联反应机理进行了初步探讨,为高效合成苯并[c]菲啶类生物碱提供了一条简便路线.     

草酸单乙酯三尖杉碱酯的合成及其在三尖杉酯类生物碱合成中的应用

用醇钠催化的酯交换方法合成了草酸单乙酯三尖杉碱酯(4),并用4和格氏试剂反应,得到合成三尖杉酯类生物碱的关键中间体α-酮酰基三尖杉碱(2),简化了已报道的一些三尖杉酯类生物碱的合成方法。     

高三尖杉酯碱和三尖杉酯碱的合成研究

天然药物高三尖杉酯碱和三尖杉酯碱是从三尖杉植物的叶和茎中分离得到的微量生物碱,是手性化合物。结构上,二者不仅含有一个共同的母核三尖杉碱,酯基侧链的α位也均为手性叔醇。因母核三尖杉碱和酯基侧链较大的空间位阻,两个结构片段的酯化偶联具有较大的挑战性。设计合成位阻较小的侧链中间体是酯化反应发生的关键。因此,化学家们相继合成了结构多样的α-羰基羧酸侧链以及含有杂环的侧链中间体,如四元内酯杂环侧链、四氢呋喃杂环侧链、六氢吡喃杂环侧链、七元内酯杂环侧链,并成功地完成了高三尖杉酯碱、三尖杉酯碱和同属其他活性生物碱的合成。本文基于本课题组的相关研究,根据侧链片段的构建策略和方法,综述了天然药物高三尖杉酯碱、三尖杉酯碱以及其他天然产物的合成研究。不仅总结了近几年来的新进展,还对我国老一辈的科学家们在此方面作出的贡献进行了回顾。     

薄层色谱法分离紫杉醇和三尖杉宁碱

建立了用薄层色谱分离紫杉醇和三尖杉宁碱的方法.方法中以正己烷-二氯甲烷-甲醇-三乙胺(体积比4.5∶3.5∶0.5∶1.0)四元体系为展开剂,在硅胶薄层板上成功地分离了紫杉醇和三尖杉宁碱,所得斑点清晰、无拖尾.同时以该体系为展开剂,使用薄层色谱法指导分离提取紫杉醇和三尖杉宁碱过程中反相色谱流分的合并,方法快速、简单、成本低,取得了满意的结果.     

异三尖杉酯碱侧链酸的合成

本文报道了异三尖杉酯碱侧链酸(3)的立体选择性合成。(R,R)-(+)-酒石酸先制成酒石酸二甲酯缩丙酮(8), 然后经烷基化、构型转换、催化加氢、碱性水解、部分酯化和酸性水解, 首次成功地得到了预期产物3。     

粉防己碱及其衍生物的全合成与结构修饰

粉防己碱为双苄基异喹啉类化合物,主要分布在防已科千金藤属植物粉防己的块根中,具有多种生物活性如镇痛消炎、降压、抗肝纤维化和抗肿瘤等。由于此类化合物具有良好的药理活性,吸引了大量有机合成和药物化学等领域学者的关注。本文从粉防己碱的全合成出发,重点综述了其C-5位、C-14及N-甲基位等位点的结构修饰的方法及产物的抗肿瘤活性研究。希望本文有助于为粉防己碱新药的研究与开发寻找一条条件温和、产率高、绿色安全、原料易得的合成路线。     

(+)-生物素全合成研究新进展

(+)-生物素是维生素B家族中的一员,自发现以来对其全合成的报道层出不穷.在最近十几年中,数十条新的合成路线和改进方法陆续报道.(+)-生物素全合成策略主要分为两类:对映选择性合成和立体专一性合成.前一策略中,通过各种反应方法对经典的Hoffmann-La-Roche-硫内酯法进行改进和完善,其中不对称催化合成的方法已成功应用于工业化生产;在后一策略中,以L-半胱氨酸为起始原料的合成途径得到了较大发展,正越来越具有工业意义.     

Remarkable Stereoelectronic Effect of the Methylenedioxy Phenyl System in the Total Synthesis of Cephalotaxine

Methylenedioxyphenyl unit displays a significant stereoelectronic effect in some key transformations in the total synthesis of cephalotaxine. The ring-strain of methylenedioxy ring may account for some important facile ring-skeleton rearrangements.     

天然产物Modhephene的全合成研究进展

综述了近年来天然产物Modhephene的全合成方法,并依据其不同的环化方法分为两大类,对每例合成方法进行了详尽的分析。     

Advances in the First Total Synthesis of Natural Flavonoids

Flavonoids, composed of a C₆-C₃-C₆ backbone, are a kind of secondary metabolites of natural medicine, which widely exist in the higher plant. They have received extensive attention from all over the world and obtained rapid development owing to widespread distribution, structural complexity, active diversity, and molecular plasticity. Total synthesis of natural products is not only one of the most driving forces in organic chemistry but also the embodiment of the development level of organic synthesis chemistry. Total synthesis research possesses not only important theoretical significance to the development of organic chemistry but also potential marketing prospects to clinical medicine and significant practical value to the development of natural medicine. Flavonoids contain flavan, chalcone, flavone, biflavone, isoflavone, xanthone, pterocarpin, homoisoflavone, flavonol, favonolignan, and some other main structure types. This article summarizes the latest research on first total synthesis, including the plant sources and biological activities, of these main structure types, so as to provide some reference for both the research of first total synthesis of natural flavonoids and the development and utilization of their medicinal value.     

Advances in the Total Synthesis of Xanthanolide‐Type Sesquiterpenoids

Xanthanolide‐type sesquiterpenoids are a diverse family of natural products isolated primarily from the genus Xanthium (Compositae). The intriguing molecular architectures and biological profiles of these natural products have rendered them attractive targets for total synthesis. This focus review aims to provide an up‐to‐date summary of progress in the chemical synthesis of xanthanolide‐type sesquiterpenoids. Different synthetic strategies to form 5/7‐cis‐ and 5/7‐trans‐bicyclic xanthanolides are presented in chronological order, with an emphasis on the key elements used to forge the characteristic 5/7‐bicyclic cores of the targets. Recent advances in the total syntheses of structurally more complicated polycyclic and dimeric xanthanolides are also discussed.     

Formal Synthesis of (−)‐Cephalotaxine

A formal synthesis of (?)‐cephalotaxine ( 1 ) by means of a highly stereoselective radical carboazidation process is reported. The synthesis begins with the protected (S)‐cyclopent‐2‐en‐1‐ol derivative 10 and uses the concept of self‐reproduction of a stereogenic center (Schemes 5 and 6). For this purpose, the double bond adjacent to the initial chiral center in 10 is converted into an acetonide after stereoselective dihydroxylation. The initial alcohol function is used to build an exocyclic methylene group suitable for the carboazidation process 8 → 7 (Scheme 7). Finally the protected diol moiety is converted back to an alkene ( 14 → 15 → 6 ) and used for the formation of ring B via a Heck reaction ( 6 →(?)‐ 16 ; Scheme 8).     

Advances in the Chemical Synthesis of Artemisinin

Artemisinin, existing in the Chinese medicinal plant Artemisia annua L., is a kind of sesquiterpenoid lactone endoperoxide. It has received extensive attention from all over the world owing to its unusual trioxane structure and potent antimalarial properties. Here we demonstrate the complete chemical synthetic pathway of artemisinin, investigated the past three decades, including the total and partial syntheses.     

Total Synthesis of the Hamigerans

The first total synthesis of hamigerans D, G, L, and N–Q has been accomplished. A convergent approach was used to build the basic tricarbocyclic ring system bearing a 5‐6‐6 structure. A sequence of oxidative cleavage, homologation, and ring regeneration provided access to the 5‐7‐6 skeleton of hamigeran G. Based on the biogenetic hypothesis, elegant and highly efficient biomimetic transformations of hamigeran G into hamigerans D, N–Q, and L were achieved.     

阿托伐他汀的全合成研究进展

介绍了近20年来利用消旋体拆分法、非对映选择性醇醛缩合法、Paal-Knorr反应、环加成法、双羰基不对称还原法等,完成阿托伐他汀全合成的研究进展。分析了各条路线的关键步骤,讨论了各方法的特点。参考文献27篇。     

Stereoselective Total Synthesis of Chrysanthemol

Recently,muchattentionhasbeenpaidtothesynthesisofbioactivenaturalproducts.Chrysanthemol,aneudesmanetypesesquiterpene,firstisolatedfromChrysanthemumindicumL.byD.Q.Yuetal.',showedstrongantiinflanunatoryactivityinmice.ThestructureandabsolutestereochemistryofchrVsanthemolwereelucidatedas1ThesyntheticrouteofchrysanthemolflomR-( )-carvoneisdepictedinScheme1:n.50%aqACOH,2hr;d)KOH,EtOH,oOC,3hr,e)Na,propanol,50"C,6hr,67.2%;66.7%i)m-CPBA/NaHCO3,CHZC12,r.t.,3.5hr,84%;TreatmentofR-( )-carvon…