Enantioselective total synthesis of marine diterpenoid clavulactone

The key steps in the synthesis of clavulactone are formation of an enantiopure cyclopentane precursor by epoxide rearrangement and intramolecular carbonyl-ene reaction, construction of the 3,4-dihydro-2H-pyran ring by intermolecular hetero-Diels-Alder reaction, closure of the eleven-membered ring, and finally generation of the lactone functionality by chemoselective allylic C(sp(3))-H oxidation.     

A formal total synthesis of the marine alkaloid aaptamine

A new strategy for the synthesis of benzo[de][1,6]naphthyridine derivative 2,3,3a,4,5,6-hexahydroaaptamine, which involves the construction of the isoquinoline ring after elaboration of the quinoline moiety, is described. Since 2,3,3a,4,5,6-hexahydroaaptamine has been previously synthesized as a key intermediate en route to the marine alkaloid aaptamine, access to this compound represents a formal total synthesis of the natural product.     

A formal total synthesis of the salicylihalamides

The synthesis of the macrolactone 23 is described. The synthesis features a diastereoselective hydroboration of the chiral alkene 17 followed by a Suzuki cross-coupling reaction with the benzoate 5. The resulting seco acid 21 was converted to the macrolactone 23 by a Mitsunobu lactonization using immobilized triphenylphosphine. The stereogenic centers in the alkene 17 were established by a Noyori reduction of the beta-keto ester 8 and an Evans aldol reaction. The synthesis illustrates the conversion of a syn aldol product to the corresponding anti product by inversion of the methyl-bearing center.     

A formal total synthesis of geneserine

The key oxindole intermediate (2) which has recently been used in a total synthesis of the alkaloid geneserine, has been prepared by a short, efficient route utilising a radical cyclisation.     

A formal total synthesis of dictyostatin

A convergent formal synthesis of the antimitotic macrolide dictyostatin has been achieved. The C11-C26 fragment of dictyostatin was prepared via convergent assembly of the central deoxypropionate motif utilizing a site- and stereoselective titanium-mediated reductive cross-coupling and an asymmetric hydrogenation of the resulting stereodefined 1,3-diene.     

A formal total synthesis of dactylol

The tetracyclic epoxide 16 was prepared in stereocontrolled fashion from 4,4-dimethylcyclohexanone, the key steps being Saegusa ring expansion of its silyl enol ether to 5, ortho ester Claisen rearrangement of 7, and cyclization of 9 without rupture of the three-membered ring. Epoxide 16 had previously been transformed into dactylol, thus completing the formal total synthesis.     

A formal total synthesis of dysidiolide

[structure] A formal total synthesis of the natural product dysidiolide is described. Starting from a Diels-Alder reaction between an enoate and a Rawal diene, the cyclohexenone 4 was synthesized. A subsequent stereospecific methyl cuprate addition established the desired trans configuration in the cyclohexane 3. Wacker oxidation of the pentenyl side chain to the diketone 17 followed by an intramolecular aldol condensation led to the bicyclic enone 2, a key intermediate in a recently reported synthesis of dysidiolide.     

A formal total synthesis of platencin

The readily available and enantiomerically pure trienes 12 undergo a thermally induced intramolecular Diels-Alder reaction to give the corresponding mixture of compounds 13 and 14. This mixture has been elaborated to an advanced intermediate associated with Nicolaou's recently reported total synthesis of the natural enantiomeric form of the antibiotic platencin (2).     

Total synthesis of marine diterpenoid stolonidiol

Marine dolabellane diterpenoid stolonidiol was synthesized from l-ascorbic acid. The method for this total synthesis involves formation of the bicyclo[2.2.1]heptane derivative using a diastereoselective sequential Michael reaction, formation of cyclopentane derivative by the retro-aldol reaction and construction of an 11-membered carbocyclic ring through the intramolecular Horner–Wadsworth–Emmons reaction.     

A formal total synthesis of leucascandrolide A

A convergent synthesis of the macrocyclic core of the marine macrolide leucascandrolide A has been accomplished.     

A formal total synthesis of crocacin C

An efficient total synthesis of a potent antifungal and moderate cytotoxic agent crocacin C is described. The synthesis involves the generation of four contiguous stereogenic centres via desymmetrization of a meso bicyclic dihydrofuran using asymmetric hydroboration.     

A scaleable formal total synthesis of dehydrogliotoxin

A formal total synthesis of the epidithiodiketopiperazine natural product, dehydrogliotoxin (2), utilizing an intramolecular ring closure to form key intermediate 5 is described.     

A novel formal total synthesis of cephalotaxine

A formal total synthesis of cephalotaxine (CET), the parent structure of antileukemia Cephalotaxus alkaloids, was achieved through a novel synthesis of the pentacyclic amino enone 4 by a rapid annulation of readily available beta-(3,4-methylenedioxy)phenethylamine (2), delta-valerolactone, and bromoacetone.     

Asymmetric total synthesis and formal total synthesis of the antitumor sesquiterpenoid (+)-eremantholide A

[structure: see text]. A new asymmetric total synthesis of (+)-eremantholide A is reported in which a Hoveyda-Grubbs ring-closing metathesis (RCM) reaction is used to assemble the nine-membered oxonin ring, and an enolate alkylation between the 3(2H)-furanone 2 and O-triflate 3 is exploited for C(9)-C(10) bond construction. An Evans asymmetric aldol reaction and a Sharpless asymmetric epoxidation served to stereoselectively install the C(6), C(7), and C(8) stereocenters of the target structure.     

A formal total synthesis of the telomerase inhibitor dictyodendrin B

A formal synthesis of the telomerase inhibitory marine pyrrolocarbazole alkaloid dictyodendrin B is described. The key features are consecutive palladium-catalyzed cross-coupling reactions and intramolecular reductive coupling reaction to construct the pyrrolo[2,3-c]carbazole framework.     

Enantioselective formal total synthesis of roseophilin

[formula: see text] An enantioselective formal total synthesis of roseophilin 3 is presented. The 13-membered ring of macrotricycle 1 was formed via an efficient ring-closing metathesis reaction of bicycle 4. A palladium-catalyzed methoxycarbonylation reaction of enol triflate 5 was utilized to functionalize the right-hand ring of bicycle 2. The allyl substituent was introduced by a radical allylation of alpha-bromoketone 17.     

A formal total synthesis of (±)-aphidicolin

A concise formal total synthesis of (±)-1$\text{via}$ the furan-terminated, epoxide-initiated cationic cyclization of 4 is described.