Synthesis of the JKLM-ring fragment of ciguatoxin

A stereoselective synthesis of the LM-ring fragment has been achieved starting from a sugar derivative. A stereoselective synthesis of the JKLM-ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex, and spiroketalization reaction.     

Preparative solid state chemistry. Recent developments

A survey of recent developments in preparative solid state chemistry shows that, with a knowledge of structural chemistry and reactivity patterns of solids, it is possible to synthesize a variety of new solids possessing novel structures. A distinction is made between synthesis ofnew solids and synthesis of solids bynew methods. Three new routes to solid state synthesis are recognized: the precursor method, and topochemical methods involving redox and ion-exchange reactions. The low-temperature topochemical methods enable synthesis of metastable phases that are inaccessible by the high temperature route. Several illustrative examples of solid state synthesis from the recent literature are presented.     

A stereoselective synthesis of (-)-viridiofungin A utilizing a TiCl(4)-promoted asymmetric multicomponent reaction

A stereoselective synthesis of (-)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia-Kocienski olefination.     

Semisynthesis of dimeric proteins by expressed protein ligation

A one-pot synthesis of homodimeric proteins is described. The synthetic strategy is based on a double expressed protein ligation reaction between thioester peptides and a new bis-cysteinyl linker. The protocol was also applied to the synthesis of heterodimers.     

Synthesis of the C10-C32 core structure of spirangien A

The synthesis of the C10-C32 core structure of spirangien A is reported. The pivotal aldol coupling between both key intermediates provides a synthetic challenge in the synthesis of this complex natural product.     

An enantioselective route to paeonilactone A via palladium- and copper-catalyzed reactions

We herein report on a formal total synthesis of paeonilactone A involving palladium-, copper-, and enzyme-catalyzed reactions starting from 1,3-cyclohexadiene. The key step in the synthesis, a palladium(II)-catalyzed 1,4-oxylactonization of a conjugated diene, simultaneously introduces two of the oxygen substituents required for the target molecule. The synthesis also includes our recently developed copper(I)-catalyzed cross-coupling reaction between dienyltriflates with Grignard reagents, introducing one of the methyl groups present in the target molecule. This new approach toward paeonilactone A allows complete control of all four stereogenic centers and is the first enantioselective route toward paeonilactone A starting from an achiral substrate.     

Palladium(0)-catalysed cross-coupling of 2-trimethylsilylpyridine with aryl halides

A general method for the Hiyama coupling reaction between aryl halides and 2-trimethylsilylpyridine has been developed. These conditions have been successfully applied to the synthesis of bis-heteroaryl systems, a key disconnection for the pharmaceutical industry in the synthesis of drug-like molecules.     

Total synthesis of dermostatin A

The concise total synthesis of dermostatin A is described. Highlights include a two-directional application of the asymmetric acetate aldol method developed in our lab, a novel diastereotopic-group-selective acetal isomerization for terminus differentiation, and a selective cross-metathesis reaction between a terminal olefin and a trienal. A study of the scope and viability of similar cross-metathesis reactions is also described. The synthesis is convergent and utilizes fragments of roughly equal complexity.     

Oxidative cyclizations: the asymmetric synthesis of (-)-alliacol A

A tandem anodic coupling-Friedel-Crafts alkylation strategy has been used to rapidly complete the asymmetric synthesis of alliacol A. The anodic oxidation reaction allowed for the generation of a new bond between two nucleophiles. In the synthesis, the absolute stereochemistry of the final natural product is set relative to a methyl group that is incorporated early in the sequence using an asymmetric Michael reaction.     

Synthesis of the glucuronide metabolite of ABT-751

A linear synthesis of the glucuronide metabolite of ABT-751 was replaced with a convergent synthesis that features direct glycosidic coupling between the aglycone and a trichloroacetimidate glucuronyl donor. Structural elucidation of a unique and unexpected difluoroboron complex of the desired glycosidic coupling product along with optimization of the synthetic steps is described.     

Efficient and straightforward preparation of a building block for (−)-teubrevin G synthesis via chemically diversed oriented synthesis

A rapid and efficient methodology to highly functionalised molecular units well suited as scaffolds for diversity-oriented molecular construction in the synthesis of natural products is reported herein. A key macrocyclic intermediate in the synthesis of the neo-clerodane diterpene (−)-teubrevin G was successfully synthesized in a 5-step sequence in a 70% overall yield using a novel intramolecular coupling between an allylborating agent and a 1,5-dialdehyde moiety.     

Total Synthesis of an Immunomodulatory Phosphoglycolipid from Thermophilic Bacteria

A method for the stereocontrolled synthesis of a bacterial phosphoglycolipid (PGL 1 ) isolated from thermophilic bacteria is described. The key features of the synthesis include a highly α‐selective glycosylation reaction between a trichloroacetimidate donor and a D ‐lyxose‐derived primary alcohol acceptor and the late‐stage incorporation of the phospholipid.     

Evaluation of asymmetric Diels-Alder approaches for the synthesis of the cyclohexene subunit of CP-225,917 and CP-263,114

Asymmetric synthesis of a functionalised cyclohexenone required for total synthesis of CP-225,917 and CP-263,114 is reported, using a Lewis acid-promoted Diels-Alder reaction between a 2-silyloxy-1,3-diene and a dienophile bearing an oxazolidinone auxiliary. A novel method for appendage of the exocyclic malonate unit, via cyclopropane ring opening, is also described.     

Concise total synthesis of the marine natural product ageladine A

A total synthesis of ageladine A has been achieved by exploiting a Pictet-Spengler-type condensation between 2-aminohistamine and 4,5-dibromo-2-formylpyrrole as the key step.     

Stereodivergent Synthesis of Piperidine Alkaloids by Ring‐Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels–Alder Cycloadducts

A general methodology for the stereoselective synthesis of 2‐(2‐hydroxyalkyl)piperidine alkaloids by ring‐rearrangement metathesis of nitroso Diels–Alder cycloadducts is reported. The approach is illustrated by the formal synthesis of porantheridine and the total synthesis of andrachcinidine through a diastereodivergent allylation of an N‐alkoxy bicyclic lactam. The asymmetric synthesis of the latter alkaloid provides new insights into the configurational stability of cycloadducts between chloronitroso reagents and cyclopentadiene.     

Total Synthesis of Leucosceptroids A and B

Leucosceptroids A and B are sesterterpenoids with potent antifeedant and antifungal activities. A more efficient gram‐scale total synthesis of leucosceptroid B and the first total synthesis of leucosceptroid A are presented. The key transformations include an aldol reaction between a substituted dihydrofuranone and an (S)‐citronellal‐derived aldehyde, a SmI₂‐mediated intramolecular ketyl–olefin radical cyclization, and final‐stage alcohol oxidation.     

Asymmetric synthesis and structure-activity studies of the fungal metabolites colletorin A,colletochlorin A and their halogenates analogues

The first asymmetric total synthesis of both enantiomers of the natural products colletorin A and colletochlorin A is presented. The proposed methodology is based on the coupling reaction between highly substituted aromatic Gilman cuprates and optically active allyl bromides, in turn obtained by Sharpless asymmetric dihydroxylation. The latter ensured a high degree of regio- and stereocontrol in the enantioselective step of the synthesis. The same synthetic strategy has been also applied for the preparation of differently halogenated synthetic analogues of colletochlorin A in high enantiomeric purity. The enantioselective synthesis of colletorin A and colletochlorin A allows to reliably assign their absolute configuration. Preliminary assessment of their herbicidal and insecticidal properties evidence the possibility to modulate the bioactivity of these compounds, highlighting its dependence on both the absolute stereochemistry and the halogen nature.     

Heteroannulation of Arynes with α‐Amino Imides: Synthesis of 2,2‐Disubstituted Indolin‐3‐ones and Application to the Enantioselective Total Synthesis of (+)‐Hinckdentine A

A novel heteroannulation reaction between α‐amino imides and in situ generated arynes has been developed for the synthesis of 2,2‐disubstituted indolin‐3‐ones. An enantioselective total synthesis of the marine alkaloid (+)‐hinckdentine A was subsequently accomplished using this reaction as a key step. A catalytic enantioselective Michael addition of an α‐aryl‐α‐isocyanoacetate to phenyl vinyl selenone was employed for the construction of the enantioenriched α‐quaternary α‐amino ester.     

Synthesis of 1,1‐Diborylalkenes through a Brønsted Base Catalyzed Reaction between Terminal Alkynes and Bis(pinacolato)diboron

A method for the synthesis of 1,1‐diborylalkenes through a Brønsted base catalyzed reaction between terminal alkynes and bis(pinacolato)diboron has been developed. The procedure allows direct synthesis of functionalized 1,1‐diborylalkenes from various terminal alkynes including propiolates, propiolamides, and 2‐ethynylazoles.     

Preparation of shape-persistent macrocycles with a single pyridine unit by double cross-coupling reactions of aryl bromides and alkynes

A double Sonogashira-type coupling reaction between aryl bromides and alkynes using a catalytic Pd/XPhos (2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl) system was introduced as an efficient method for the synthesis of shape-persistent macrocycles (SPMs). This approach is advantageous in the synthesis of SPMs with a single pyridine unit.