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%。     

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。     

异三尖杉酯碱类似物-酒石酸甲酯三尖杉碱酯的合成

异三尖杉酯碱系三尖杉属植物中所含具有抗肿瘤活性的四种生物碱之一,其本身的合成已有三种不同的方法^[1-3]先后获得成功。但是,在这些合成中,生成的异三尖杉酯碱都是立体异构体的混合物。据报导^[4.5]异三尖杉酯碱及其某些类似物对癌细胞具有明显的抑制作用。为了考察这类化合物的结构与抗癌活性之间的关系,并为异三尖杉酯碱立体异构体构型的确定提供依据,我们进行了(2R,3R)-酒石酸甲酯三尖杉碱酯Ⅵ和(2S,3S)-酒石酸甲酯三尖杉碱酯Ⅶ的合成。     

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。     

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。     

半合成差向异构体——三尖杉酯硷和表三尖杉酯硷的制备型高效液相色谱分离及鉴定

半合成三尖杉酯硷系利用三尖杉属植物中含量较高的三尖杉硷(构型为3S、4S、5R),进行人工合成所得的三尖杉酯硷(Harringtonine)Ⅰ(2＇R)     

以手性1-氮杂螺[4.4]壬烷骨架为中间体合成(-)-Cephalotaxine的研究进展

高三尖杉酯碱因具有较好的抗癌和抗肿瘤活性而受到广泛重视，2012年，美国FDA正式批准其用于临床治疗慢性粒白血病适应症。三尖杉碱为高三尖杉酯碱的母核结构，具有5个环系以及3个相邻的手性中心。三尖杉碱分子结构的特殊性以及高三尖杉酯碱良好的药理活性，促使众多研究小组对其展开了不对称合成研究。本文综述了以手性1-氮杂螺[4.4]壬烷骨架为中间体，合成(−)-Cephalotaxine的研究进展。      

福建三尖杉碱及其类似物的半合成研究: 一个立体选择性反应的发现

从表台湾三尖杉碱(epiwilsonine)(3)合成福建三尖杉碱(cephalofortunaine)(4)时, 发现3在稀醋酸中子0℃加1:10溴-四氯化碳混合试剂能直接生成2-O-乙酰基福建三尖杉碱的一对2-C差向异构体1与2(9:1), 产率及两个产物比例随着温度而变化。同时报道了类似物5, 6, 10和11的半合成与这类化合物^1H NMR中质子的归属。     

N-二异丙基磷酰基-N-[2-(3′,4′-亚甲二氧苯基)]乙基甘氨酸的单晶结构的研究

三尖杉酯碱是一种具有显著抗肿瘤活性的化合物。在以磷酰基、磺酰基、乙酰基作N-苯乙基甘氨酸上氨基的保护基进行分子内酰化的Friede-Crafts反应,合成三尖杉酯碱母核-(N-7,8-亚甲二氧苯并-3-氮杂环庚酮-1)时所得结果相差甚远。特别是用磷酰基保护甘氮酸衍生物可以避免脱羰,顺利地进行内酰化反应,对合成三尖杉酯碱的母核有重要的意义。为了阐明磷酰基对氨基酸中氮原子上的孤对电子的稳定作用,我们测定了N-二异丙基磷酰基-N-[2-(3’,4’-亚甲二氧苯基)]乙基甘氨酸的单晶结构。     

苯直接一步氧化合成苯酚

苯直接一步氧化合成苯酚是开辟苯酚合成路线具有挑战性的热点课题之一.近年来研究和开发了以N2O、H2O2和O23种不同氧化剂体系为核心和主流的苯氧化合成苯酚路线.本文详细综述了目前3种不同氧化体系的研究进展和趋势,分析了各种合成路线的特点和工业应用前景.以N2O为氧化剂合成苯酚路线,技术趋于成熟,但N2O来源受限而影响其经济性和推广应用;以H2O2为氧化剂合成苯酚路线,是环境友好过程,有开发潜力,但技术还很不成熟,而且也因H2O2价格昂贵带来了经济成本问题;以O2为氧化剂、氢气为还原剂体系合成苯酚路线,是环境清洁可持续发展制备路线,具有很好的开发潜力,此外无机膜催化合成苯酚路线也更具吸引力.     

爱博霉素B的全合成研究进展

爱博霉素B是16元环的大环内酯类化合物,以其独特的抗癌性能和复杂新颖的化学结构而受到越来越多的化学工作者的关注,从发现至今已有许多研究小组报道了相关的全合成研究成果.本文作者综述了其合成研究进展,分析了各合成路线的关键步骤,讨论了某些路线的优缺点,并对该药的研究前景进行了展望.     

Total synthesis of (+)-amphidinolide A. Assembly of the fragments

The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.     

Rapid Generation of Molecular Complexity by Chemical Synthesis: Highly Efficient Total Synthesis of Hexacyclic Alkaloid (−)‐Chaetominine and Its Biosynthetic Implications

The efficiency becomes a key issue in today's natural product total synthesis. While biomimetic synthesis is one of the most elegant strategies to achieve synthetic efficiency and thus to approach the ideal synthesis, most biogenetic pathways are unknown or unconfirmed. In this account, we demonstrate, through the shortest and also the most efficient asymmetric total syntheses of the hexacyclic alkaloid (?)‐chaetominine to date, that on the basis of biogenetic thinking, one can develop quite efficient bio‐inspired total synthesis, which in turn serves to suggest and chemically validate plausible biosynthetic routes for the natural product. The synthetic strategy thus developed is also inspiring for the development of other synthetic methods and efficient total synthesis of other natural products.     

Facile access to some chiral building blocks. Synthesis of verbalactone and exophilin A

d-Glucono-1,5-lactone, an inexpensive carbohydrate, was elaborated into chiral building blocks readily applicable in synthesis via practical routes without involving any expensive reagents or tedious operations. Application of such chiral building blocks in total synthesis is then exemplified through construction of verbalactone and exophilin A. The latter compound has not been synthesized to date.     

澳洲栗精胺全合成研究进展

主要介绍近年来天然物澳洲栗精胺全合成研究的多种方法，包括用葡萄糖，甘露糖等不同的起始原料和不同的合成路线。参考文献１１篇。     

汉防己甲素全合成研究进展

汉防己甲素是防己科千金藤属植物粉防己中分离提取的双苄基异喹啉类生物碱,已作为临床药物用于抗风湿及阵痛、抗肺癌、抗矽肺。基于粉防己产量的限制及汉防己甲素的需求量增加,深入开展汉防己甲素的全合成研究势在必行。本文按照合成策略,对汉防己甲素的全合成方法进行了综述。      

General and efficient strategy for erythrinan and homoerythrinan alkaloids: syntheses of (+/-)-3-demethoxyerythratidinone and (+/-)-erysotramidine

[reaction: see text] A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides followed by a N-acyliminium ion promoted intramolecular cyclization, and represents one of the shortest routes to erythrinan and homoerythrinan alkaloids. As the application, the formal total synthesis of (+/-)-3-demethoxyerythratidinone and the total synthesis of (+/-)-erysotramidine have been achieved, respectively.     

抗肿瘤活性四氢异喹啉生物碱全合成研究进展

综述了近年来抗肿瘤活性四氢异喹啉生物碱Renieramycin,Ecteinascidin和Quinocarcin的全合成研究进展,对其构环顺序和方法进行了分析,对部分合成路线的优缺点进行了讨论.     

A Total Synthesis of Aliskiren

A total synthesis of aliskiren ( 20 ) was accomplished. A key in our synthesis was to use the symmetric trans‐cisoid‐trans‐bis‐lactone 1 as a precursor. It was expediently prepared by three different routes (Scheme 2). Appending the end groups and functional group transformations completed the synthesis (Scheme 3).     

A Comparative Synthetic Strategy Perspective on α-Amino Acid- and Non-Amino Acid-Derived Synthons towards Total Syntheses of Selected Natural Macrolides

Macrocyclic alkaloids (macrolides) and cyclopeptides have an immense range of applications in drug discovery research because of their natural abundance and potential biological and physicochemical properties. Presently, more than 100 approved drugs or clinical drug candidates contain macrocyclic scaffolds as the biologically active component. This review provides an interesting perspective about the use of amino acid-derived chiral pools versus other methods derived from miscellaneous synthons towards the total synthesis of non-peptidic macrolides. The synthetic routes and the key strategies involved in the total syntheses of ten natural macrolides have been discussed. Both the amino acid-derived and non-amino acid-derived synthetic routes have been illustrated to present a comparative study between the two approaches.