Total synthesis of curvulone B and a proposed structure for dothiorelone B; determination of the configuration of curvulone B and structural revision of phomopsin A

The total synthesis of curvulone B was achieved, and its absolute configuration unambiguously established, as had been determined by TD-DFT ECD calculations on the computed solution conformers. Key features of the synthesis were an olefin cross-metathesis of an α,β-unsaturated ketone as a common key building block with (R)-6-triethylsilyloxyhept-1-ene, and an intramolecular oxy-Michael addition of the hydroxyl enone obtained therefrom. An intermolecular metathesis of the enone with (S)-5-benzyloxyhept-ene also enabled us to prepare a proposed structure for dothiorelone B, thus leading to the confirmation of the structural revision of phomopsin A, a novel nine-membered cyclic phenol ether.     

A copper-carbodiimide approach to the phomopsin tripeptide side chain

A one-step copper-carbodimide elimination was used to provide the (E)-dehydroisoleucine moiety in the phomopsin side chain stereoselectively. An efficient approach to the phomopsin tripeptide side chain was developed to be used in the total syntheses of phomopsins A and B.     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.     

Enantioselective total synthesis of ustiloxin D

Ustiloxin D and phomopsin A are potent antimitotic agents that bind to tubulin and interfere with cellular microtubule function. A synthetic strategy has been developed to allow access to both of the natural products as well as a variety of variants of the ustiloxin and phomopsin family members in order to provide sufficient quantities for biological studies. Herein we report the enantioselective total synthesis of ustiloxin D using a longest linear sequence of 20 steps. Four of the five stereocenters were set using catalytic asymmetric methodologies. In particular, Evans's new Al-catalyzed asymmetric aldol reaction facilitated access to both syn and anti products corresponding to the different benzylic stereochemistries found in ustiloxins and phomopsins. In addition, due to its high functional group tolerance, Trost's Pd-mediated etherification was used to construct the chiral tertiary alkyl-aryl ether. Taken together, these synthetic strategies allow us to use densely functionalized intermediates to realize an efficient synthesis of ustiloxin D.     

Elaboration of vinblastine hybrids using a reactive in situ generated N-carboxyanhydride

Hybrids of vinblastine and phomopsin, designed by a molecular modelling study, were elaborated in order to target tubulin. The key step of the synthesis (fragmentation and insertion of vindoline) was mediated by an internal N-carboxyanhydride (or O-acylcarbamate). This reaction was diastereospecific and addition of silver salts could reverse the diastereoselectivity. Even if the synthesized compounds are inactive, this synthesis represents an original example of a C-N fragmentation mediated by a N-carboxyanhydride.     

Antifungal Cytosporone Derivatives from the Mangrove-Derived Fungus Dothiorella sp. ML002

Chemistry of Natural Compounds - A new cytosporone derivative, dothiorelone P (1), and one known analog, dothiorelone E (2), were isolated from fermentation culture of the mangrove-derived fungus...     

A novel and efficient route for the preparation of atorvastatin

A novel and efficient synthetic method of atorvastatin was described.The key step of the synthesis was the construction of the olefin linkage between the chiral side chain and skeleton via a Horner-Wadsworth-Emmons reaction,resulting in the advanced intermediate of atorvastatin under hydrogenation of the olefin over Pd/C.This novel method is more useful for the practical synthesis of atorvastatin than its document reported methods.     

A short synthesis of (+)-cyclophellitol

[reaction: see text] A new synthesis of (+)-cyclophellitol, a potent beta-glucosidase inhibitor, has been completed in nine steps from D-xylose. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 5-deoxy-5-iodo-xylofuranoside followed by a highly diastereoselective indium-mediated coupling with ethyl 4-bromocrotonate. Subsequent ring-closing olefin metathesis, ester reduction, olefin epoxidation, and deprotection then afford the natural product. This constitutes the shortest synthesis of (+)-cyclophellitol reported to date.     

A concise approach towards the synthesis of WS75624 A and WS75624 B via the cross-metathesis of vinyl-functionalized thiazoles

Synthetic approach towards precursors of WS75624 A and WS75624 B, two potent endothelin converting enzyme (ECE) inhibitors and potential antihypertensive agents, is reported featuring a key cross-metathesis between a vinyl-functionalized thiazole and a terminal olefin. As the two natural products only differ by the nature of their hydroxyalkyl side-chain, our convergent strategy enable the synthesis of key intermediates of both molecules in a limited amount of steps.     

Total synthesis of Carpatamides A–D

A synthetic strategy was developed for the synthesis of the common core structure of Carpatamides A–D. The total synthesis of Carpatamides A and C was completed in 6 steps and of Carpatamides B and D in 7 steps, by employing the Wittig olefination, olefin cross metathesis and acid amine coupling reactions as key steps.     

Enhancement of enantioselectivity by THF in asymmetric mo-catalyzed olefin metathesis. Catalytic enantioselective synthesis of cyclic tertiary ethers and spirocycles

Mo-catalyzed enantioselective rearrangement of achiral cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers are reported. These olefin metathesis transformations proceed efficiently and with high levels of enantioselectivity. A noteworthy feature of these reactions is that added tetrahydrofuran exerts a remarkably positive influence on the enantioselectivity of the metathesis-based rearrangement. The first examples of catalytic asymmetric synthesis of spirocyclic structures by enantioselective olefin metathesis are also disclosed.     

F-T合成校正综合动力学模型

考虑了烯烃、醇与酸的再吸附及其非本征效应(烯烃、醇与酸在催化剂孔道中的扩散作用、物理吸附及溶解度效应)对产物分布的影响,推导了基于详细反应机理的亚甲基插入的烷基机理F-T合成校正综合动力学模型.利用文献数据对动力学模型进行了回归,获得了与文献报道结果相一致的动力学参数.由校正动力学模型计算的烷烃、烯烃、醇与酸产物分布及烯烃比、醇烃比及酸烃比与实验数据较好地吻合.动力学计算结果表明,在铁锰催化剂上,烷烃、烯烃、醇与酸生成的反应是平行竞争反应,烯烃、醇与酸在催化剂表面的再吸附及二次反应导致产物分布偏离了ASF分布.动力学研究还表明,相同碳数的醇与酸产物在催化剂表面上再吸附及二次反应的机会比相同碳数的烯烃大.通过比较相同碳数的烯烃、醇与酸的分子体积及沸点,指出了在铁锰催化剂上,低碳数的烯烃、醇与酸的再吸附及二次反应对产物分布影响的非本征效应中,烯烃、醇与酸的扩散阻力不是主导效应.     

Template synthesis of a huge macrocycle by olefin metathesis using easily accessible [Pt(PEt(3))(2)] templates

We have reported the template synthesis of a 90-membered macrocycle by olefin metathesis. The macrocycle 7 was prepared by an initial six-oxidative-addition reaction of 2 by [Pt(PEt(3))(4)]. The definite structure of a six-oxidative product was confirmed by the crystal structure. The coordination of 2,6-bis(hex-5-enyloxy)pyridine to 3 led to the hexacationic aryl complex of type 4. The metathesis of olefin-substituted pyridine with Grubbs catalyst ([PhCH==RuCl(2)(Cy(3)P)(2)]) formed the expected macrocycle 5. The olefin metathesis reaction was formed under high dilution to suppress intermolecular olefin metathesis polymerization. The detachment of the newly formed macrocycle 6, followed by reduction to alkane macrocycle 7 by using palladium on charcoal and hydrogen led to a huge macrocycle. The mild and easy access of the template protocol opens a host of potential subsequent transformations toward the construction of a variety of macrocycles.     

Synthesis of solamin type mono-THF acetogenins using cross-metathesis

The total synthesis of mono-THF acetogenins, cis-solamin A and B, and reticulatacin, was accomplished starting with muricatacin. The backbone of the mono-THF acetogenins was constructed by olefin cross-metathesis between the tetrahydrofuran moiety and γ-lactone moiety. An enzymatic kinetic transesterification procedure was successfully applied to the synthesis of an optically pure γ-lactone moiety. Notably, cis-THF compounds were obtained without using protective groups.     

Cytosporones O, P and Q from an endophytic Cytospora sp.

Cytosporones O, P and Q, together with the known compounds cytosporones B, C, D, E and dothiorelones A, B, C, and H were isolated from the ascomycete fungus Cytospora sp. during a chemotaxonomic study of fungal endophytes belonging to the related genera Cytospora and Phomopsis from Brazil. The structures were determined by NMR spectroscopy and mass spectrometry. With exception of cytosporones D, E, Q, and dothiorelone B, all compounds were consistently detected in the metabolite profiles of eight Cytospora isolates investigated; and were also produced by a distinct chemotype of Phomopsis.     

Enantio- and stereospecific syntheses of 15(R)-Me-PGD2, a potent and selective DP2-receptor agonist

The first total synthesis of 15(R)-Me-PGD2 3 is reported. The synthesis is based on the enantioselective and stereospecific syntheses of synthon 17 and its attachment to the five-membered ring by a olefin cross metathesis reaction. This approach permits the introduction of a side chain with a predetermined stereogenic center into the prostanoid ring, resulting in the synthesis of 15R-methyl prostaglandin D2 and allows rapid access to other prostanoids.     

Quantitative determination of olefin oxide, chlorohydrin, and cyclocarbonate in the presence of each other

A procedure was developed for the quantitative determination of olefin oxide, chlorohydrin, and cyclocarbonate simultaneously present in the reaction mixture of the synthesis of cyclocarbonate from olefin oxide and CO₂. To determine olefin oxide, an acetone solution of hydrochloric acid was added to a portion of the reaction mixture, and the excess of hydrochloric acid was titrated with an aqueous solution of potassium hydroxide with visual detection. The concentrations of chlorohydrin and cyclocarbonate were calculated from the data of the potentiometric titration of the same solution to which excess potassium hydroxide was added. Deceased.     

Total synthesis of (-)-salicylihalamide

A concise total synthesis of the potent cytotoxic marine natural products salicylihalamide A and B (la, b) is reported. Key steps of our approach were the asymmetric hydrogenation reactions of beta-keto esters 18 and 32 catalyzed by [((S)-BINAP)Ru-Cl2]2. NEt3 and the cyclization of the macrolide core by ring closing olefin metathesis (RCM) using the "second-generation" ruthenium carbene complex 24 as the catalyst which bears an imidazol-2-ylidene ligand. The EIZ ratio obtained in this macrocyclization reaction was determined by the protecting groups at the remote phenolic OH group of the cyclization precursor. The elaboration of the resulting cycloalkene 37 into the final target involved a CrCl2-mediated synthesis of vinyliodide 49 which, after deprotection, did undergo a copper-catalyzed cross-coupling process with the (Z,Z)-configurated carboxamide 42 to form the labile enamide moiety of 1. Compound 42 was derived from a palladium-catalyzed Negishi coupling between butynylzinc chloride and 3-iodoacrylate 39 followed by a Lindlar reduction of enyne 40 thus obtained and a final aminolysis of the ester group.     

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B,Lipiarmycin A3)

Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug‐resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18‐membered macrolactone is reported herein. The key reactions include ring‐closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium‐sized fragments, thus leading to a flexible yet convergent synthetic route.     

Synthesis of a new isoxazolidine from diacetone glucose

The synthesis of a new furo-pyran-based isoxazolidine, making use of an intramolecular oxime–olefin cycloaddition (IOOC) reaction, is reported here, starting from diacetone glucose.