The first total synthesis of the potent antibiotic disciformycin B( 2)i sd escribed, which is exceptionally isomerization-prone and transforms into disciformycinA (1)e ven undern otably mild conditions. To outweigh this bias, the approach to 2 hingedo nt he use of as ilyl residue at C4 to lock the critical double bond in place and hence insure the integrity of the synthetic intermediates en route to 2.This tactic was instrumental for the preparation of the buildingb locks and formation of the macrocyclic ring via ring closing alkyne metathesis (RCAM). To make the end game successful, however,i tp rovedn ecessary to cleave the C-silyl protecting group off;i tw as at this stage that the exceptional sensitivity of the target becamef ully apparent.The ever-faster emergenceo fr esistantp athogenic bacteria renders the visionofaplanetliberated from infectious diseases by effective broad-spectrum antibiotics increasingly unlikely. [1] Therefore the search for new activep rinciples with different modes of action is warranted, if not even vital in the longer run. [2,3] It is against this backdropt hat the recent reports on the myxobacterialm etabolites of the disciformycina nd gulmirecin families must be seen (Figure 1). [4][5][6][7] These compounds exhibit considerable activity against Gram-positiveb acteria, including several methicillin-or vancomycin-resistant Staphyllococcus aureus strains;m ost notably,t hey seem to address an as yet unknown biological targeta nd hence likelyp rovide new opportunities in the quest for antibiotics devoid of cross-resistance with approved drugs.The constitution and stereostructure of these remarkable polyketides were determined by two independentg roups, each of which masterfullyc omplemented the spectroscopica rgumentsb ya na nalysis of the encoding gene cluster. [4,5] One of these studies suggestedt hat disciformycin B( 2,F igure 1) represents the primary product of biosynthesis;i nterestingly, 2 also proved considerably more active than its sibling 1 in an assay comprising eight different bacterial strains. [4] Yet, preliminary evidence suggests that 2 is fragile and subject to irreversible double bond migration, which is likelyd riven by the highers tabilityo ft he trisubstituted enoate in 1 compared to the disubstituted enonemotif in the parent compound 2.Intrigued by the biologicalp romisea nd the synthetic challenge forecastb yt hese reports, [4,5] we embarked into ap rogram aiming at ac hemical investigation of this familyo fn ew lead compounds. To tal synthesis is the first step to be taken in order to assess the ingrained metastabilityo f2 in more detail and scout possible remedies.A tthe same time, it is desirable to identify promising sites for late-stage modification to be addressed in then ext phase of the project. [8] The actualc onquest of disciformycin Aa nd Bo utlined below meets many of these goals;m ost notably,i tr evealed some remarkable chemical caprices of these target compounds,w hich will guide our ongoing efforts at establishing am ore scalabler ou...

Vetiver oil, produced on a multiton‐scale from the roots of vetiver grass, is one of the finest and most popular perfumery materials, appearing in over a third of all fragrances. It is a complex mixture of hundreds of molecules and the specific odorant, responsible for its characteristic suave and sweet transparent, woody‐ambery smell, has remained a mystery until today. Herein, we prove by an eleven‐step chemical synthesis, employing a novel asymmetric organocatalytic Mukaiyama–Michael addition, that (+)‐2‐epi‐ziza‐6(13)en‐3‐one is the active smelling principle of vetiver oil. Its olfactory evaluation reveals a remarkable odor threshold of 29 picograms per liter air, responsible for the special sensuous aura it lends to perfumes and the quasi‐pheromone‐like effect it has on perfumers and consumers alike.

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates ArNCO ( Ar=2,6-iPr C H ) and ArNCO ( Ar=2,6-Ph -4-tBuC H ) with Piers' borane (HB(C F ) ). While hydroboration of smaller isocyanates such as ArNCO leads to isocyanate-N/B FLP adducts, hydroboration of the bulkier ArNCO allows isolation of the substrate-free aminoborane with a short, covalent N-B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a "normal" FLP along the reaction pathway, supported by high-level DFT studies and variable-temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid-base interaction.

The five-membered zirconacycloallenoids 2 react rapidly with dihydrogen under mild conditions to yield the corresponding (s-cis-conjugated diene)zirconocenes 3. The reaction involves splitting of the H(2) molecule between the metal center and a ligand carbon atom.

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates iPr2ArNCO (iPr2Ar=2,6‐iPr2C6H3) and Ph2tBuArNCO (Ph2tBuAr=2,6‐Ph2‐4‐tBuC6H2) with Piers’ borane (HB(C6F5)2). While hydroboration of smaller isocyanates such as iPr2ArNCO leads to isocyanate—N/B FLP adducts, hydroboration of the bulkier Ph2tBuArNCO allows isolation of the substrate‐free aminoborane with a short, covalent N−B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a “normal” FLP along the reaction pathway, supported by high‐level DFT studies and variable‐temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid–base interaction.