乌檀属吲哚生物碱Norketoyobyrine的全合成

以色胺为起始原料,经还原、酯水解、脱羰-消除四步反应,分别以16%和14%的总收率,实现了乌檀属吲哚生物碱Norketoyobyrine及其N-甲基衍生物的全合成。各中间体及产物的结构通过¹H NMR,¹³C NMR及HRMS等分析方法确证。     

吲哚生物碱Alsmaphorazine D的全合成

<正>Angew.Chem.Int.Ed.2015,54,879~882夹竹桃科鸡骨常山属植物广泛存在于非洲和亚洲的热带地区,目前已成为熟知的富含独特单萜吲哚骨架结构的杂环生物碱的主要来源.此类生物碱由于其生源合成途径的有趣性以及抗肿瘤、抗菌、抗炎、止咳和抗疟疾等显著的生理活性引起了化学家们很大的研究兴趣.最近,日本星药科大学药学系Morita课题组从生长于马来西亚的鸡骨常山属植物的呼吸根叶的提取物中分离得到了一类新的生物碱结构,并将其命名为Alsmaphorazines A~E.在此家族中,Alsmaphorazines D和E具有一种新颖的六氢吡咯[2,3-b]吡咯并二氮杂双环[3.3.1]壬烷核心结构,并且分子中含     

亚胺参与的Diels-Alder反应及其在生物碱全合成中的应用

在通过Diels-Alder反应建立各种含氮六员环的反应中, 亚胺是一个最有用的亲双烯试剂. 该法应用简便、并显示出较好的位置选择性和立体选择性. 对其在生成碱类全合成中的应用也作了综述.     

亚胺参与的Diels-Alder反应及其在生物碱全合成中的应用

在通过Diels-Alder反应建立各种含氮六员环的反应中,亚胺是一个最有用的亲双烯试剂。该法应用简便、并显示出较好的位置选择性和立体选择性。对其在生物碱类合成中的应用也作了综述。     

灯台生物碱Strictamine的全合成

灯台生物碱具有复杂多样的结构和显著的生理活性,针对此类分子的化学合成引起了有机化学界的广泛关注。其中的代表性化合物strictamine在结构上具有笼状的methanoquinolizidine核心骨架和C7位全碳季碳手性中心,在合成上具有重要挑战。关于该化合物的全合成已有超过40年的研究历史,而直到最近两年才取得突破性的进展。本文针对2016年以来关于strictamine的三条全合成和四条形式合成路线进行简要介绍,主要剖析了各条合成路线中的关键策略和反应,并对进一步的研究进行了展望。     

百部生物碱的全合成

百部生物碱是从直立百部(Stemona sessilifolia)和其近缘植物的根部分离得到一类生物碱。在分子结构上,这类生物碱通常具有[1, 2-b]吡咯并[1, 2-a]氮杂卓的母核结构,并且由于在母核的多个位置有不同的取代基,从而表现出结构及生物活性的多样性,因而百部生物碱的全合成研究引起国内外化学家的关注。但是由于百部生物碱结构中具有复杂的多环结构及多个手性中心,此类天然产物的全合成研究具有较大的挑战。近年来,化学家们相继开发并应用高对映选择性的反应及串联反应等高效的策略,完成了多个百部生物碱的全合成研究,为百部生物碱进行深入生物活性研究及开发利用奠定了坚实的基础。本文基于本课题组的相关研究内容,综述了各种类型百部生物碱近年来的全合成研究进展。     

石松属生物碱Sieboldine A的全合成研究进展

简要介绍了石松属生物碱Sieboldine A的分离、生物活性及结构特征,综述了目前国内外对于Sieboldine A的全合成研究进展,详细论述了各个实验组在引入羟胺缩醛结构及构建cis-6/5稠环体系所采取的不同策略,并介绍了一价金催化的串联烯炔环化反应、路易斯酸催化的semipinacol重排和二碘化钐引发的自由基Pinacol偶联反应在Sieboldine A全合成中的应用。     

3,4-桥环吲哚类生物碱的合成研究进展

取代的吲哚类天然产物是自然界中普遍存在的一类杂环化合物,由于其具有广泛的生理活性,以及相当一部分作为重要的临床使用药物,100多年以来,吲哚的合成及官能团化一直是有机合成化学家关注的一个重要领域.在众多吲哚类生物碱中,含有3,4-桥环吲哚骨架的天然产物占据了相当一部分,由于其独特的结构和良好的生物活性,这些分子引起了有机合成化学家的广泛兴趣.重点概述了构建3,4-桥环骨架的主要合成方法和策略,并对一些方法在天然产物全合成中的应用作简要介绍.     

倍半萜生物碱Dendrobine的全合成研究进展

石斛碱(Dendrobine)是一类从传统中药金钗石斛中分离得到的具有Picrotoxane倍半萜碳骨架的生物碱类天然产物.由于该化合物具有多环稠合和七个连续立体中心的结构特点,以及镇痛和退热等药理活性,引起了众多有机合成化学家和药物化学家的关注.五十年来,天然产物Dendrobine的药理活性研究和化学合成不断涌现,...     

吲哚类生物碱的合成研究进展

吲哚类生物碱是具有吲哚分子骨架的一类化合物,具有多种良好的生理活性。文章综述了近年来新发现吲哚类生物碱的合成研究进展,介绍了(-)-Arboricine,(±)-cis-Trikentrin A,(-)-Corynantheidol等化合物的合成方法。     

Total Synthesis of Indole Alkaloid Alsmaphorazine D

A concise total synthesis of rac‐alsmaphorazine D has been described for the first time. The efficient synthetic strategy features four key transformations: 1) a catalytic intramolecular oxidative cyclization for the δ‐lactamindole backbone; 2) an oxidative cyclic aminal formation for the hexahydropyrrolo[2,3‐b]pyrrole framework; 3) a transannular radical cyclization for the construction of the diazabicyclo[3.3.1]nonane structure; and 4) a one‐pot desilylation/double epimerization reaction that affirms the relative stereochemistry.     

Total Synthesis of Tetrahydroquinoline Alkaloid （＋）-Angustureine

( )-(S)-Angustureine was synthesized using a CuI-catalyzed coupling reaction of iodobenzene with an enantiopure β-amino ester as the key step. The overall yield is 36% in 7 linear steps.     

Asymmetric Synthesis of Fortucine and Reassignment of Its Absolute Configuration

A convergent and enantioselective synthesis of fortucine was achieved from the starting materials tyrosine methyl ester and 3‐hydroxy‐4‐methoxybenzaldehyde. The synthesis is based on two key steps mediated by a hypervalent iodine reagent. This work has enabled us to reassign the absolute configuration of the natural product reported in the literature.     

Synthetic Studies on Erythrina Alkaloids: Formal Total Synthesis of (+)-3-Demethoxyerythratidinone

A formal asymmetric synthesis of (+)-3-demethoxyerythratidinone (1) is reported using the key intermediate 3 as the starting material, which is available from L-malic acid by a known method.

Total Synthesis and Determination of the Absolute Configuration of (+)‐Omaezakianol

The proof of the pudding : The first asymmetric total synthesis of the marine tetracyclic oxasqualenoid (+)‐omaezakianol features a convergent olefin cross‐metathesis between a monotetrahydrofuran fragment and a triepoxy alkene, and cascade oxacyclizations of a triepoxy alcohol to form the right‐hand three ether rings. The total synthesis proved the absolute configuration of (+)‐omaezakianol to be that shown.

     

Enantioselective Total Synthesis of (+)‐Steenkrotin A and Determination of Its Absolute Configuration

The first enantioselective total synthesis of (+)‐steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh‐catalyzed O?H bond insertion followed by an intramolecular carbonyl‐ene reaction, two sequential SmI₂‐mediated Ueno–Stork and ketyl–olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro‐aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)‐steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis.     

Total Synthesis of (+)‐Gracilamine Based on an Oxidative Phenolic Coupling Reaction and Determination of Its Absolute Configuration

The enantioselective total synthesis of (+)‐gracilamine ( 1 ) is described. The strategy features a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza‐Michael reaction to construct the ABCE ring system. The configuration at C3a in 1 was controlled by the stereocenter at C9a, which was selectively generated (91 % ee) by an organocatalytic enantioselective aza‐Friedel–Crafts reaction developed by our research group. This synthesis revealed that the absolute configuration of (+)‐gracilamine is 3aR, 4S, 5S, 6R, 7aS, 8R, 9aS.     

Synthesis of the Strychnos Alkaloid (−)‐Strychnopivotine and Confirmation of its Absolute Configuration

The first enantioselective synthesis of (?)‐strychnopivotine from a known and inexpensive phenol has been achieved in 15 steps. The strategy is based on a new diastereoselective aza‐Michael‐enol‐ether cascade desymmetrization of a dienone, guided by a removable lactic acid‐derived chiral auxiliary. Synthesis involves a phenol dearomatization, a conjugated silicon addition, a stereoselective double reductive amination, and two Heck‐type carbopalladations as key steps. The absolute configuration of the natural compound, which, to date, has been uncertain, was confirmed by using circular dichroism (CD) spectroscopy and X‐ray analyses.     

Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594

A highly convergent approach was developed to achieve the first asymmetric and scalable total synthesis of FD‐594, a complex polycyclic xanthone natural product from Streptomyces sp. TA‐0256, in a longest linear sequence (LLS) of 20 steps. The trans‐9,10‐dihydrophenanthrene‐9,10‐diol fragment (B‐C‐D ring) was generated through a new strategy involving asymmetric dihydroxylation followed by Cu‐mediated oxidative cyclization. Late‐stage stereoselective glycosylation assembled the angular hexacyclic framework with a β‐linked 2,6‐dideoxy trisaccharide fragment.