Enantiocontrolled synthesis of the epoxycyclohexenone moieties of scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase

The epoxycyclohexenone moieties 2 and 3b of scyphostatin (1), a potent and specific inhibitor of neutral sphingomyelinase, were synthesized in enantiomerically pure forms starting from (−)-quinic acid (11). The synthetic method features (i) the preparation of the olefin masked enones 25 and 29, the precursors for the key aldol-type coupling reaction, (ii) the efficient and stereocontrolled aldol-type coupling reactions between 25 (or 29) and benzaldehyde (8) and Garner's aldehyde analogue 9 to deliver alcohols 23 and 24, respectively, both of which possess the requisite asymmetric quaternary carbon center at the C6 position, and (iii) the stereospecific S_N2-type epoxide ring formation of the mesylates 35 and 47 under mild basic conditions to produce the targeted compounds 2 and 3b, respectively.     

Synthesis of the stereogenic triad of the halicyclamine A core

We describe herein our progress toward the synthesis of halicyclamine A, which possesses very interesting biological activities and has never been synthesized. For this purpose, we proposed a stereoselective Diels-Alder reaction as a key step for the establishment of the stereogenic triad of the bis(piperidinyl) core of this molecule. A series of NMR studies was then conducted to establish the correct stereochemical assignment subsequent to the Diels-Alder reaction.     

Total synthesis of 4-epi-atpenin A5 as a potent nematode complex II inhibitor

It is clear that atpenins and their analogs are useful chemical tools for elucidation of complex II functionality and that they could act as lead compounds for the development of novel helminth complex II-specific inhibitors. Recently, we discovered 4-epi-atpenin A5 as a potent nematode complex II inhibitor during our SAR studies of atpenin A5. This result led us to embark on a concise total synthesis of 4-epi-atpenin A5. In this study, we describe the total synthesis of 4-epi-atpenin A5. Importantly, this was more concise and practical synthesis than our previous total synthesis of atpenin A5.     

Synthesis and convenient functionalisation of pyridazinofurocoumarins: nitrogenated isosters of potent DNA inhibitors

Pyridazino[3,4-h]psoralens and pyridazino[3,4-j]angelicins are prepared in good yield from resorcinols through a direct, easy and generally applicable synthetic route. The key step in this route is the inverse electron-demand Diels-Alder reaction between linear or angular furocoumarins and 3,6-bis(methoxycarbonyl)-1,2,4,5-tetrazine to give the dicarboxymethylated tetracycles. The ester group in the peri position with respect to the oxygen in the furan ring can be regioselectively transformed to give primary or secondary amides. Similarly, the two ester groups in the tetracycle can be transformed in a high-efficiency process to give bis-amides that can be either symmetrical (from the same amine) or unsymmetrical (from two different amines).     

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。     

The first total synthesis and structural determination of TMC-66

The first total synthesis and structural determination of TMC-66, an ECE inhibitor, was achieved in short steps by efficient construction and coupling of segments. The oxidative coupling with phenols attaching to electron-withdrawing groups was realized with a novel copper(II) reagent.     

Synthesis of a novel bicyclic scaffold inspired by the antifungal natural product sordarin

A simplified bicyclic scaffold inspired by the antifungal natural product sordarin was designed and synthesized which maintains the carboxylic acid/aldehyde (or nitrile) pharmacophore. Docking studies with the target for sordarin, the fungal protein eukaryotic elongation factor 2 (eEF2), suggested that the novel scaffolds may bind productively. A densely functionalized chiral cyclopentadiene was constructed in 8 steps and utilized in a Diels-Alder reaction with acrylonitrile. The resulting [2.2.1] cycloheptene was transformed into a scaffold possessing vicinal carboxylic acid and nitrile groups, with orientations predicted to provide high affinity for eEF2. The synthetic approach disclosed here sets the stage for a renewed medicinal chemistry campaign against eEF2.     

Synthesis of BCD tricyclic analogues of the novel cardiac glycoside rhodexin A

A concise synthesis of novel cardiac glycoside analogues of rhodexin A, 14 and 24, having the BCD tricyclic system is described. The key constructive step is an inverse-electron demand Diels-Alder reaction of the silyl enol ether 4 and the 2-acetyldiene, 7 and 15.     

Enantioselective synthesis of 1-(R)-hydroxypolygodial and its 9α epimer, 1-(R)-hydroxyisotadeonal

The enantioselective synthesis of 1-(R)-hydroxypolygodial and its epimer at C-9 is described. α-Ionone was the starting material. Key steps of these syntheses included a Corey-Bakshi-Shibata oxazaborolidine-mediated reduction and a stereoselective Diels-Alder reaction. No vanilloid activity was detected for both compounds in assays on VR1 vanilloid receptor in HEK cells transfected with the human VR1.     

Synthesis and structure determination of a novel lithium copper vanadate LiCu2VO4(OH)2

A novel lithium copper vanadate LiCu₂VO₄(OH)₂ (I) and Volborthite Cu₃V₂O₇(OH)₂ are two phases obtained at 170 °C by hydrothermal synthesis during the study of the CuO; V₂O₅; Li₂O; H₂O system. Compound (I) crystallizes in the orthorhombic system, with the space group P2₁2₁2₁ (No. 19) and with the unit-cell parameters a=9.6086(2) Å, b=8.4482(2) Å, c=5.8938(1) Å. The structure was determined from powder by an “ab initio” method using the EXPO software and refined with GSAS, a Rietveld refinement package. Wave-like layers of rutile-type copper chains sharing vertex with the neighbor chains, are linked into a three-dimensional framework by rows of alternating tetrahedra of vanadium and trigonal bipyramids of lithium which share edges and vertices with the copper octahedra.     

Wallichanol类天然产物ABC环系合成研究

Wallichanol是一类具有独特桥环结构的二萜天然产物.以2-甲基-1,3-环己二酮作为起始原料,通过高立体选择性的Diels-Alder反应和金催化的炔烃碳环化反应构建Wallichanol的ABC三环核心骨架,共七步路线,总收率为42％.该合成工作为Wallichanol类天然产物全合成奠定了研究基础.     

Chemical synthesis and structure determination of venom toxins

Venom toxins are receiving growing interests as novel therapeutics and biophysical probes. This review briefly discusses recent advances in the chemical synthesis and structure determination of venom toxins.     

A new approach to the bicyclo[4.3.0] ring system of natural products from the liverwort: total synthesis of (±)-chiloscyphone and (±)-isochiloscyphone

Construction of the tricyclic derivative 5, a common intermediate for the synthesis of sesquiterpenoids 1-4, was accomplished by using the intramolecular Diels-Alder reaction. Availability of 5 was demonstrated by effective total synthesis of chiloscyphone 1 and isochiloscyphone 2.     

基于双“click”反应的树枝状化合物的一锅法合成

将叠氮和炔基之间Cu(I)催化的“click”反应以及蒽和马来酰亚胺之间的Diels-Alder反应相结合, 采用“一锅法”技术合成出结构完美且外围含有亲水性寡聚乙二醇(OEG)链段的树枝状化合物4, 产率为75%. 利用核磁共振氢谱、碳谱、紫外、荧光光谱以及MALDI-TOF质谱等对产物进行了表征与分析, 并利用凝胶渗透色谱(GPC)对其纯度进行了测试.     

Synthesis of marchantin C, a novel microtubule inhibitor from liverworts

Recently, remarkable microtubule inhibitor and anti-tumor activities of the bisbibenzyl marchantin C—isolated from liverworts like Marchantia polymorpha since 1983—were found. In this Letter we describe the first and efficient total synthesis of this subtype of bisbibenzylic compounds with two biarylether connections. The structure was confirmed by the spectroscopic data which were analyzed carefully to exclude any errors in arene connection and substitution pattern.     

富烯的合成及其应用研究进展

综述了富烯的合成方法及富烯的应用.     

Syntheses of PDE3A inhibitor ORG9935 and determination of the absolute stereochemistries of its enantiomers by X-ray crystallography

Two synthetic methods were developed for the synthesis of PDE3A inhibitor ORG9935. The first one proceeds in six steps and 34% overall yield and the second one in five steps and an overall yield of 69% starting from commercially available starting material 5,6-dimethoxybenzo[b]thiophene-2-carboxylic acid (6). The enantiomers of ORG9935 were separated by chiral column chromatography and the absolute stereochemistry of the (+)-enantiomer, ORG20865 was determined by X-ray crystallography to possess the (S)-configuration. The (?)-enantiomer, ORG20864, was therefore assigned the (R)-stereochemistry. The biologically less active (+)-isomer ORG20865 was converted to racemic ORG9935 under basic conditions, which then can be separated again into the enantiomers. The crystal structure of ORG20865 is notable for having the highest Z′ for any known pharmaceutical substance.