Regioselective synthesis of the bridged tricyclic core of Garcinia natural products via intramolecular aryl acrylate cycloadditions

[reaction: see text] Two different routes to the tricyclic core of Garcinia-derived natural products are described. The first approach is based on a tandem Claisen/Diels-Alder rearrangement and delivers the desired lactone 14. The second approach, employing a Wessely oxidation/Diels-Alder protocol, leads to the same caged heterocycle, albeit with modified constitution.     

A biomimetic strategy for the synthesis of the tricyclic dibenzofuran-1,4-dione core of popolohuanone E

A concise synthesis of the complete tricyclic dibenzofuran-1,4-dione aromatic core of popolohuanone E has been demonstrated by mild base treatment of a biquinone intermediate, thus establishing a biomimetic route to this family of heterocyclic ring systems and the total synthesis of popolohuanone E.     

A ketal-tethered RCM strategy toward the synthesis of spiroketal related natural products

An unconventional approach to construct spiroketals and spiroaminals via ring-closing metathesis [RCM] of cyclic ketals and aminals, respectively, is described here. This method possesses a good generality with no loss of stereochemical integrity at the spirocenter under the standard RCM conditions. This approach has been applied to the synthesis of an insect pheromone to demonstrate its synthetic potential, and also to the synthesis of the C11-epi-C22-C23 fragment in spirastrellolide A. Both are proof-of-concept applications to feature a ketal-tethered RCM as an alternative strategy for construction of spiroketals.     

Convergent enantioselective synthesis of the tricyclic core of phomactin A

[reaction: see text] The tricyclic core of phomactin A was synthesized from 6,6-dimethyl-2-cyclohexen-1-one. Key reactions include the addition of a cyclohexenyllithium reagent to an epoxyaldehyde and a regioselective intramolecular epoxide opening to install the oxadecalin core.     

A convergent synthesis of the tricyclic core of the dictyosphaeric acids

The first synthetic route to the tricyclic core of the dictyosphaeric acids has been established starting from readily available (S)-(-)-4-(tert-butyldimethylsilyloxy)cyclohexenone and involving 9 steps, including a ring-closing metathesis to produce a 13-membered macrolactone, and a doubly tethered intramolecular Michael addition.     

Regioselective synthesis of the tricyclic core of lateriflorone

An efficient synthetic approach to the tricyclic core 8 of lateriflorone is described. Essential to the synthesis was the implementation of a biomimetic tandem Claisen/Diels-Alder reaction that produced the desired tricyclic scaffold as a single isomer. A rationalization of the excellent regio and stereoselectivity of this transformation is also proposed. [reaction: see text]     

Total synthesis of natural products using a desymmetrization strategy

Total syntheses of SB-203207 (1) and sphingofungin E (2) were accomplished by utilizing an asymmetric desymmetrization strategy to introduce multiple stereogenic centers into meso starting compounds in a single step. Thus, rhodium carbenoid-mediated CH insertion into 3 provided the bicyclo[3.3.0]framework 4 for 1, while organocatalyst-mediated bromolactonization of 5 afforded 6 for the synthesis of 2. Similarly, we utilized desymmetric rhodium nitrenoid-mediated aziridination reaction of 5 to obtain a key intermediate required for a total synthesis of pactamycin (29), a complex aminocyclopentitol antibiotic featuring six contiguous stereogenic centers.     

Synthesis of the spiroacetal core of the cephalosporolide family of natural products

The synthesis of four possible stereoisomers of the spiroacetal core of the natural products cephalosporolides H and I and penisporolides A and B is described. The key steps involve the use of Sharpless asymmetric dihydroxylation to install the desired stereochemistry of the γ-lactone ring and an oxidative radical cyclisation to form the spiroacetal ring system.     

Intramolecular Diels-Alder reaction leading to tricyclic derivatives as intermediates of natural products synthesis

Tricyclic compounds 4a and 4b possessing a bicyclo[4.3.0] moiety, were successfully synthesized by using the intramolecular Diels-Alder reaction. The siloxy- rather than acyloxy-substituents increased the ratio of the endo-cylcoadducts 10 and 12. The oxygen substitution of 9 influenced conformation of the transition state, which was stereochemically restricted by the butenolide moiety. In addition, 9b carrying a hydroxyl group also produced 10b in a similar ratio to 9a. Compound 11 was the only exo-adduct produced in all of the entries.     

The cycloaddition strategy for the synthesis of natural products containing carbocyclic seven-membered rings

Highly substituted carbocyclic seven-membered rings are frequently found in natural products and their synthesis represents a significant challenge to the synthetic chemist. Direct intramolecular cyclization of these systems often proves difficult and this fact has catalyzed the development of a variety of strategies based on a convergent intermolecular cycloaddition strategy. This concept article discusses the major cycloaddition approaches utilized to access these types of structures and primarily focuses on examples employed in the synthesis of natural products.     

Concise synthesis of the tricyclic core of lycoposerramine S

The tricyclic core of lycoposerramine S has been synthesised in 10 steps from a symmetrical cyclohexadiene precursor by way of a desymmetrising free-radical cyclisation and iodocyclisation.     

Vinigrol: a compact, diene-transmissive Diels-Alder strategy to the tricyclic core

A short (six steps from 17), versatile route to the tricyclic core of Vinigrol is described. A Lewis acid catalyzed and self-assembled Diels-Alder (LACASA-DA) reaction from the homoallylic cross-conjugated trienol 15 with N-methylmaleimide afforded the monoadduct 17 with diastereo-, regio-, and chemoselective control. Oxidation and installation of an acetylene (Ohira's reagent) followed by further manipulations afforded trienone 24. The second intramolecular Diels-Alder (at 45 degrees C) reaction assembled the tricyclic skeleton 25 directly. The configuration of 25 was confirmed by X-ray analysis.     

Enantiospecific synthesis of the tricyclic core structure of lippifolianes

An enantiospecific synthesis of the [6.6.3]-tricyclic carbon framework, 2,6,6,9-tetra-methyltricyclo[5.4.0.0^2,4]undecane, present in the sesquiterpenes lippifolianes and the diterpenes cyclosclareol, metasequoic acids and parguerols, starting from the readily available monoterpene (R)-carvone, is described.     

Synthetic study of manzamine B: synthesis of the tricyclic central core by an asymmetric Diels-Alder and RCM strategy

Tricyclic core of manzamine B was successfully synthesized through asymmetric Diels-Alder reaction and RCM strategy. Cr-salen-F complex was found to be the most effective catalyst in DA reaction of aminodienes with heterocyclic dienophiles to give up to 97% ee. In the construction of 11-membered ring by RCM, first-Grubbs cat. gave better stereoselectivity.     

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described. The pyrido[1,2-a]indole core was demonstrated to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel annulation strategy was showcased in a concise formal synthesis of three fascaplysin congeners.

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described.     

An efficient stereoselective route to the construction of tricyclic core structure towards the synthesis of the sesquiterpenes of the seco-prezizaane family

An efficient stereoselective approach to the construction of a hydrindane derivative having a bridged lactone is described toward the synthesis of the sesquiterpenes of the seco-prezizaane family. The key step involves RO-RCM of a norbornene derivative.     

A carbohydrate-based approach for the total synthesis of 1,3-polyol/alpha-pyrone antifungal natural products

[Chemical reaction: see text] An elimination and stereoselective hydrogenation of alpha-D-glucoheptonic-gamma-lactone derivative has been applied to prepare a differentially protected anti,anti-1,3,5-triol system, the utility of which has been extended for the total synthesis of anti-fungal 1,3-polyol/alpha-pyrone natural products.