Application of Olefin Cross-Metathesis to the Synthesis of Biologically Active Natural Products

19 pages Merci a Bentam Science Publishers Ltd. d'accepter le dépôt en archives ouvertesAn overview of the use of olefin cross-metathesis in the synthesis of biologically active natural products is presented. The diverse examples are organized according to the outcome of the olefin constructed by the cross-metathesis reaction: this olefin can be either present in the final product, reduced, engaged in other transformations, or involved in tandem processes

Study of cascade ring-closing metathesis reactions en route to an advanced intermediate of Taxol

A highly functionalized intermediate in the synthesis of Taxol has been synthesized, which features the tricyclic core and the required oxygen substituents at C1, C2, C7, C10 and C13. The key step, a ring-closing dienyne metathesis (RCDEYM) reaction, has been thoroughly optimized to favor the tricyclic product over the undesired bicyclic product resulting from diene metathesis

Selective hydrogenolysis of benzyl ethers in the presence of benzylidene acetals with Raney nickel

3 pages.International audienceA simple method to remove selectively a benzyl group protecting a hydroxyl function in the presence of a benzylidene acetal by catalytic hydrogenolysis with Raney nickel is reported. This method was successfully applied to the synthesis of the C1–C14 fragment of dolabelides

Condensation of beta-hydroxy sulfones and vinyl sulfones with aldehydes and ketones using phenyllithium as base

4 pages Merci à Elsevier pour l'autorisation de déposer cet article sur HAL.Condensation of beta-hydroxysulfones 7a-b with aldehydes and ketones were performed with diverse bases. Phenyllithium proved to be optimum, giving yields of compounds 9-12a-e ranging from 67 to 80%. Condensation of vinyl sulfones 15a-c with aldehydes also worked very well with PhLi, and the resulting adducts 16a-d were transformed into protected syn 1,3-diols flanked with an olefin at the a carbon by a new conjugate addition/elimination sequence. These products are models for the C21-C25 sub-unit of Dolabelides

Synthesis of Model BC Bicycles of Taxol Using C10-C11 Ring-Closing Metathesis Strategy

6 pagesInternational audienceModel BC ring-systems of taxol 23b and 28b, which lack an oxygenated substituent at C7, have been efficiently synthesized. The key step is a ring-closing metathesis (RCM) to form the 8-membered B ring between C10 and C11. Comparison of the metathesis reaction in this route with the RCM used in a previous study with similar substrates is highlighted

Tailoring polyethers for efficient post-polymerization functionalization by cross metathesis

Olefin cross metathesis is reported for the first time to attach small molecules to a range of novel polyethers with a poly(ethylene glycol) backbone and pendent alkene groups, allowing for a loading of up to one compound per monomer unit. These polymers are tailored to prevent the occurrence of self metathesis (reaction of the polymer with itself) by varying the substitution on the pendent alkenes, thus steering their reactivity toward olefin cross metathesis. Efficient functionalization has been observed for a range of coupling partners as a proof of concept for the use of olefin metathesis to graft small and larger molecules to polyethers for drug delivery. This approach also paves the way for the use of olefin cross metathesis as an efficient method to functionalize a wide variety of polymers with pendent olefin groups

Water-compatible synthesis of 2-trifluoromethyl-1,3-dioxanes

A water-compatible method for the diastereoselective synthesis of 2-trifluormethyl-1,3-dioxanes is described. The reaction proceeds under mild reaction conditions using simple inorganic bases; it has a very good substrate scope and can be performed with different Michael acceptors. Additionally, the reaction products can be further functionalized, showing an excellent perspective for future applications

Olefin cross metathesis as a versatile method for the facile functionalization of porous polymers

Olefin cross metathesis has been employed for the first time for the postpolymerization chemical modification of porous polymers. High quality microspheres of poly(divinylbenzene) were synthesized by the precipitation polymerization of divinylbenzene-55 in porogenic solvents, and the olefin cross metathesis reactions of the pendent (polymer-bound) vinyl groups not consumed by polymerization were performed with diverse coupling partners in dichloromethane using the Grubbs 2 catalyst, leading to microspheres decorated with a wide range of functional groups

Diastereoselective synthesis of an advanced intermediate of thapsigargin and other 6,12-guaianolides using a RCEYM strategy

A new and flexible approach toward the synthesis of 6,12-guaianolide anticancer drugs such as trilobolides or thapsigargin has been developed that could be applied to the preparation of analogues with a modified ring system. The synthesis starts from commercial 2-methylcyclopentane-1,3-dione, only relying on diastereoselective reactions for the construction of the stereogenic centers at C1, C3, C6, and C10 and features a high-yielding ring-closing enyne metathesis (RCEYM) step for the formation of the [5,7] bicyclic core