Total synthesis of branimycin: an evolutionary approach

The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization.     

Total synthesis of (+)-lithospermic acid by asymmetric intramolecular alkylation via catalytic C-H bond activation

The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.     

Catalytic Asymmetric Total Synthesis of Exiguolide

The catalytic asymmetric total synthesis of (−)-exiguolide, a complex 20-membered macrolide embedded with a bis(tetrahydropyran) motif, is reported. The convergent synthesis involves the construction of the C1–C11 tetrahydropyran segment via catalytic asymmetric allylation and Prins cyclization, and the formation of the C12–C21 phosphonate segment via catalytic asymmetric cyclocondensation reaction and Johnson–Claisen rearrangement. The synthesis of 15-epi-exiguolide is also described.     

Imidazolium‐functionalized SBA‐15 type silica: efficient organocatalysts for Henry and cycloaddition reactions

We report the synthesis of mesoporous SBA‐15 type silica bearing ionic imidazolium substructures. Surface functionalization was achieved via post‐synthesis grafting reactions using bis‐silylated imidazolium precursors onto a mesoporous SBA‐15 type silica support. The grafting reactions were monitored via solid‐state NMR spectroscopy, nitrogen sorption, transmission electron microscopy and thermogravimetry. Post‐synthesis grafting is the most convenient way to achieve highly stable functionalized solids displaying excellent accessibility of the immobilized functional groups combined with high chemical stability. The solids obtained via post‐synthesis grafting reactions appeared as highly efficient and reusable heterogeneous organocatalysts for Henry reactions and the cycloadditions of CO₂ to epichlorohydrin. Copyright © 2013 John Wiley & Sons, Ltd.     

A mild biosynthesis of lactones via enantioselective hydrolysis of hydroxynitriles

We have developed a biocatalytic method to produce lactones and related compounds via the enzymatic hydrolysis of γ- and β-hydroxynitriles. The synthesis is a mild, general, and environmentally friendly way to enantioselectively hydrolyze nitriles with commercially available nitrilase enzymes. The synthesis of four pheromones is demonstrated via a one-step method.     

Enantiomeric synthesis of the key synthon of the oviposition-deterring pheromone of Rhagoletis cerasi L

A convenient and enantioselective synthesis of ethyl (8RS, 15R)-8-acetoxy-15-hydroxyhexadecanoate15 via a chemoenzymatic approach has been described. The salient features of the synthesis were operational simplicity, use of easily accessible materials, and excellent enantiocontrol via lipase catalyzed acetylation of 2-alkanol.     

The facile synthesis of benzothiazolylideneacetates and 1,4-benzothiazines through a highly controllable oxidation of benzothiazolylacetates

The synthesis of benzothiazolylideneacetates and 1,4-benzothiazine was found to be highly controllable via simple exchange of corresponding oxidants. It turned out that the treatment of benzothiazolylacetates with m-CPBA gave 1,4-benzothiazines via oxidative ring expansion process, and with DDQ gave benzothiazolylideneacetates via dehydrogenation, in good yield, respectively. The structures of both skeletons were confirmed by their X-ray diffractions. A previously reported method for the synthesis of benzothiazolylideneacetates was thus proved to be incorrect.     

Expedient total synthesis of pyrrothine natural products and analogs

This paper describes an expedient and straightforward total synthesis of the two pyrrothine natural products holomycin (7 steps, 11% overall) and xenorhabdin I (7 steps, 11% overall) and analogs thereof via a common late-stage intermediate. The pathway proceeds via the pyrrothine hydrochloride intermediate (6 steps, 17% overall) which also gave access to very fast synthesis of analogs as demonstrated by the synthesis of , and (7 steps, 11-12% overall).     

Organophosphorus π-conjugated materials: the rise of a new field

The synthesis and electronic properties of new linear organic π-conjugated systems incorporating phosphole rings are described. Well defined α,α′-(phosphole-thiophene) oligomers possess low HOMO-LUMO gaps and their optical and electrochemical properties can be tuned via chemical modifications of the P-atoms. The physical properties of these compounds make them valuable materials for OLED’s. The coordination ability of phosphole-based dipoles has been exploited for the synthesis of efficient multipolar NLO-phores. Lastly, phospholes have been used for the synthesis of assemblies exhibiting through-bond interaction between two π-systems via P-P σ-skeletons.     

An efficient regioselective copper catalyzed multi-component synthesis of 1,3-disubstituted pyrazoles

An efficient synthesis of unsymmetrically substituted 1,3-pyrazole derivatives has been developed via three-component coupling reaction involving 3-(dimethylamino)-1-phenylprop-2-en-1-one, hydrazine, and aryl halides in one pot process exhibiting high regioselectivity. The pyrazole synthesis proceeds via a sequential series of reactions such as Michael addition, heterocyclization, dehydration, and Ullmann cross-coupling.     

Practical routes to the triarylsulfonyl chloride intermediate of a β3 adrenergic receptor agonist

A β₃ adrenergic receptor agonist was prepared on a multi-kilogram scale in high yield and purity via a convergent synthesis. A key intermediate in this synthesis was an arylthiazolylbenzenesulfonyl chloride. The triaryl segment of this sulfonyl chloride was assembled at the thiazole ring via coupling of α-haloketone and thiobenzamide precursors (Hantzsch synthesis). Three strategies for introducing the para-sulfonyl chloride moiety were developed and evaluated. The sulfonation/chlorination and diazotization/chlorosulfonylation routes were found the most efficient.     

Synthesis of tert-butyl peresters from aldehydes by Bu4NI-catalyzed metal-free oxidation and its combination with the Kharasch-Sosnovsky reaction

A new tert-butyl peresters synthesis directly from aldehydes and TBHP was developed via Bu(4)NI-catalyzed aldehyde C-H oxidation. Mechanistic studies suggest that the protocol proceeds via a radical process. Combining the method with the Kharasch-Sosnovsky reaction offers a practical approach for the synthesis of allylic esters from simple aldehydes and alkenes via a two-step one-pot procedure.     

Total synthesis of microcin B17 via a fragment condensation approach

The total synthesis of the 43 amino acid antibacterial peptide Microcin B17 (MccB17) is described. The natural product was synthesized via a convergent approach from a heterocycle-derived peptide and peptide thioester fragments prepared via Fmoc-strategy solid phase peptide synthesis (SPPS). Final assembly was achieved in an efficient manner using two Ag(I)-assisted peptide ligation reactions to afford MccB17 in excellent overall yield.     

Synthesis of cyclic hemiketals and spiroketals from dioxanorbornanes

[reaction: see text] A new method for the synthesis of substituted pyranone hemiketals from dioxanorbornanes via SmI(2) is described. Also reported is a synthesis of spiro[4.5]ketals from analogous intermediates via acid-promoted deprotection/ketalization.     

A concise synthesis of tetrabenazine: an intramolecular aza-Prins-type cyclization via oxidative C-H activation

A concise synthesis of tetrabenazine and dihydrotetrabenazine is described. The key feature of this synthesis is the intramolecular aza-Prins-type cyclization of an amino allylsilane via oxidative C-H activation.     

Stereoselective synthesis of macrolide-type antibiotics from epoxy amides. Synthesis of the polypropionate chain of streptovaricin u

The synthesis of the polypropionate chain of Streptovaricin U (1) is described utilizing a new approach for the stereoselective synthesis of the macrolide-type antibiotics via sulfur ylides.     

Synthesis of 2-aminothiazoles from styrene derivatives mediated by 1,3-dibromo-5,5-dimethylhydrantoin (DBH)

An efficient procedure for the synthesis of 2-aminothiazoles via DBH-mediated oxidative cyclization of styrenes and thioureas is reported. Various alkenes were successfully transformed to the corresponding 2-aminothiazoles in yields of 10–81% via a two-step one-pot manner using DBH as both the bromine source and oxidant. The method can be readily carried out in gram-scale and successfully applied to the synthesis of anti-inflammatory drug fanetizole using styrene as starting material.     

Enantioselective Synthesis of C−O Axially Chiral Diaryl Ethers by NHC-Catalyzed Atroposelective Desymmetrization**

Axially chiral diaryl ethers, a distinguished class of atropisomers possessing unique dual C−O axis, hold immense potential for diverse research domains. In contrast to the catalytic enantioselective synthesis of conventional single axis bearing atropisomers, the atroposelective synthesis of axially chiral ethers containing flexible C−O axis remains a significant challenge. Herein, we demonstrate the first N-heterocyclic carbene (NHC)-catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde-containing diaryl ethers. Mechanistically, the reaction proceeds via NHC-catalyzed desymmetrization strategy to afford the corresponding axially chiral diaryl ether atropisomers in good yields and high enantioselectivities under mild conditions. The derivatization of the synthesized product expands the utility of present strategy via access to a library of C−O axially chiral compounds. The temperature dependency and preliminary investigations on the racemization barrier of C−O bonds are also presented.     

Synthesis of the stereoisomers of 17,21-dimethylheptatriacontane - sex recognition pheromone of the tsetse fly

The title compounds were obtained both by application of directed resolution via diastereomeric amides and a novel asymmetric synthesis via ester enolates.     

The sulfinyl moiety as an internal nucleophile. Part 8: Efficient, stereospecific synthesis of (+)-polyoxamic acid

A straightforward and stereospecific synthesis of (+)-polyoxamic acid is disclosed. The key step of the synthesis involves the regio- and stereospecific bromohydration of an olefin via intramolecular participation by the sulfinyl group.