A short access to the skeleton of Elisabethin A and formal syntheses of Elisapterosin B and Colombiasin A.

A short stereoselective synthesis of the Elisabethin A skeleton 4 is described, which opens a formal access to the diterpenes Elisapterosin B and Colombiasin A as well. Key reactions were an intermolecular endo-selective Diels-Alder reaction to generate the decalin part of the molecule, a chemo- and diastereoselective allylation of an aldehyde with allylzinc, a palladium ene annulation of the cyclopentane ring, and a novel sulfonium ylide induced fragmentation of a polycyclic ketone. Additional insights have been gained for the crucial epimerization at C-2.

Light-mediated total synthesis of 17-deoxyprovidencin.

An asymmetric synthesis of the diterpenoid 17-deoxyprovidencin is described. Key steps include an aldol addition, a base-catalyzed Wipf-type furan formation, a Z-selective ring-closing metathesis for macrocyclization, a photochemical E/Z isomerization to a highly strained and conformationally restricted ring system, and the stereoselective formation of two epoxides on the ring.

Trying to rationalize total synthesis.

Total synthesis has been held in high esteem for many decades. In recent years, however, public opinion has turned more and more skeptical. In particular, long and uneventful sequences towards complex yet useless targets are considered a waste of resources and are refused funding.

A palladium-catalyzed carbo-oxygenation: the bielschowskysin case.

An asymmetric synthesis of an advanced tetracyclic intermediate toward the synthesis of bielschowskysin (1) is described. A biomimetic [2 + 2]-photocyclization was used to establish the cyclobutane core of bielschowskysin. Macrocyclization under Heck conditions led to an unprecedented carbo-oxygenation of a 1,1-disubstituted double bond.

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.

Application of the Rodriguez-Pattenden photo-ring contraction: total synthesis and configurational reassignment of 11-gorgiacerol and 11-epigorgiacerol.

A stereospecific photochemical ring contraction was used as the key step in the first total synthesis of the marine pseudopteranyl diterpene 11-gorgiacerol and its 11-epimer. The synthesis allowed the correction of the configurations that had been misassigned in the literature. In addition, some novel pseudopteranyl derivatives have been made.

A non-photochemical approach to the bicyclo[3.2.0]heptane core of bielschowskysin.

An asymmetric synthesis of the tricyclic core (-)-1 of the marine diterpene bielschowskysin is described. In particular, a methodology was developed to introduce the crucial quaternary center at C-12.

Efficient and scalable one-pot synthesis of 2,4-dienols from cycloalkenones: optimized total synthesis of valerenic acid.

A mild and selective one-pot procedure to provide 2,4-dienols from simple cycloalkenones in high yields is described. This transformation is based on the in situ formation of acid-labile allylic alcohols, which on treatment with trifluoroacetic acid undergo a formal [1,3]-hydroxy migration to form diastereo- and enantiomerically enriched 2,4-dienols. The usefulness of this protocol is demonstrated in a short synthesis of valerenic acid.

Synthesis of the lycopodium alkaloid (+)-lycoflexine.

The first total synthesis of (+)-lycoflexine (1), a constituent of Lycopodium clavatum var. inflexum , has been accomplished in eight steps with 13% overall yield. Our synthesis covers four one-pot reactions, including a tandem Sakurai/aldol sequence, a novel hydroboration/oxidation procedure, a deprotection/transannular Mannich reaction, and as a highlight, a tandem catalysis cascade combining an enynene ring-closing metathesis and a selective hydrogenation.

In pursuit of a competitive target: total synthesis of the antibiotic kendomycin.

Kendomycin is a novel polyketide having a unique quinone methide ansa structure and an impressive biological profile. Herein we provide a chronological overview of the synthetic work towards the title compound. Thus far, over a period of about eight years, eight groups worldwide have published on their synthetic efforts resulting in five total syntheses, one formal synthesis, and a number of fragment syntheses.

Syntheses and antibacterial properties of iso-platencin, Cl-iso-platencin and Cl-platencin: identification of a new lead structure.

Platencin is a novel antibiotic which is active against multiresistant pathogens. We describe efficient syntheses of three platencin analogues of varying activities which allow further conclusions about the pharmacophoric part of the molecule. The unnatural antibiotic iso-platencin, which is about as active as natural platencin, but much more selective, was identified as a new lead structure.

From silphinenes to penifulvins: a biomimetic approach to penifulvins B and C.

The biomimetic total synthesis of penifulvins B and C uses a meta-photocycloaddition as a key step which gives rapid access to the fenestrane-type carboskeleton with control of an onring quaternary stereocenter. The route is concise, stereocontrolled, scaleable, and flexibile and requires only one protecting group.

Ring-closing metathesis and photo-fries reaction for the construction of the ansamycin antibiotic kendomycin: development of a protecting group free oxidative endgame.

Two convergent total syntheses of the ansa-polyketide (-)-kendomycin (1) are described. The syntheses benefit from the use of readily available and cheap starting materials. Highly complex diastereoselective Claisen-Ireland rearrangements were used to introduce the (E)-double bond and the C16-Me group.

Synthesis of (Z)-trisubstituted olefins by decarboxylative grob-type fragmentations: epothilone D, discodermolide, and peloruside A.

Methyl-branched (Z)-trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxide- induced Grob-type fragmentation as an easy access to trisubstituted olefins.

Total syntheses of (+)-echinopine A and B: determination of absolute stereochemistry.

The first total syntheses of the novel 3,5,5,7-sesquiterpenoids (+)-Echinopine A (1) and B (2) were achieved. Thereby the proposed structures were confirmed, and the absolute stereochemistry was determined. The key features are (1) the stereoselective installation of the vinyl-moiety on the concave side of the bicyclo[3.

A desymmetrization approach toward highly oxygenated cis-decalins.

The cis-decalin core 2 of the antibiotic branimycin has been prepared by desymmetrization of diepoxynaphthalene 4. The key steps involve two successive S(N)' opening of the oxa-bridges. An improved procedure for the synthesis of 4 is also described.

Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D.

Discriminating elimination: A new method for the synthesis of methyl-branched trisubstituted Z olefins, a structural motif in many polyketides with anticancer activity, relies on an (-)OH-induced decarboxylative Grob-type fragmentation (see scheme; Ms = mesyl). The starting materials are beta-mesyloxy lactones with a quaternary alpha center, which are prepared by aldol reactions in a diastereo- and enantioselective manner.

The laulimalide family: total synthesis and biological evaluation of neolaulimalide, isolaulimalide, laulimalide and a nonnatural analogue.

We herein describe in full detail the first total synthesis of the antitumor agents neolaulimalide and isolaulimalide as well as a highly efficient route to laulimalide. A Kulinkovich reaction followed by a cyclopropyl-allyl rearrangement is used to install the exo-methylene group. The C(2)-C(16) aldehyde fragment is coupled with the C(17)-C(28) sulfone fragments by a highly (E)-selective Julia-Lythgoe-Kocienski olefination to deliver the key intermediates of all three syntheses.

A nine-step total synthesis of (-)-platencin.

Within 1 year, platencin, a recently discovered antibiotic, has become a highly competitive synthetic target, due to its promising bioactivity and its unusual complex molecular architecture. Herein, a particularly concise total synthesis of platencin starting from inexpensive perillaldehyde is described. The key features of this approach are (1) a highly diastereoselective Diels-Alder reaction with Rawal's dieneforming the first all-carbon quaternary center, (2) a ring-closing metathesis to generate the strained tricylic skeleton, (3) a hydration/dehydration strategy to efficiently shift the endocyclic alkene to the exoposition, and (4) a 1,4-addition of a hindered ketone enolate to methyl acrylate to create the second all-carbon quaternary center.

Total synthesis of valerenic acid, a potent GABAA receptor modulator.

The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of Valeriana officinalis, is described. The compound is a potent modulator of the GABA(A) receptor and may thus be useful in the treatment of various dysfunctions of the central nervous system. The synthesis is enantio-, diastereo-, and regiocontrolled and utilizes an enyne-RCM, a metal-coordinated Diels-Alder reaction, a hydroxy-directed Crabtree hydrogenation, and a Negishi methylation as key steps.