RESUMEN
Photoredox-catalysed hydroxymethylation of ß-ketoesters substituted by an allyl subunit on the α-position afforded directly the corresponding bicyclic lactones possessing both a hydroxy group and an unsaturation. A subsequent regioselective iodoetherification led to the formation of original [3.3.3] propellane structures. Substitution of the iodine atom by various nucleophiles afforded highly functionnalized structures including triazolomethyl derivatives.
RESUMEN
Novel access to oxaspiro[n,3,3]propellanes has been developed from bicyclic lactones directly prepared by a photochemical hydroxymethylation or alternatively by a three-step sequence. Thanks to the presence of additional hydroxy- and propargylic groups, a second cyclization catalyzed by silver or bismuth salts, led to the propellane structure which was finally transformed into spiranic derivatives by a Simmons-Smith reaction or condensation with α-ketoesters.
RESUMEN
A new and straightforward synthesis of the C1-C7 core fragment of nhatrangin A was achieved in 14 steps from achiral 3-hydroxybenzaldehyde, without the need of chiral reagents or enzymatic resolution to introduce the chiral centers. The key asymmetric steps include in particular a highly enantioselective organocatalyzed Michael addition on an aryl vinyl ketone, a Sharpless asymmetric epoxidation and a subsequent regioselective ring opening of the resulting chiral epoxide. This work represents the first formal enantioselective synthesis of nhatrangin A.
RESUMEN
The total synthesis of bistramideâ A and its 36(Z),39(S) and 36(Z),39(R) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether-forming reaction for the spiroketal fragment, a kinetic oxa-Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL-60 cells, thus suggesting that these effects are independent activities of the natural product.
Asunto(s)
Acetamidas/síntesis química , Acetamidas/farmacología , Piranos/síntesis química , Piranos/farmacología , Compuestos de Espiro/síntesis química , Acetamidas/química , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Ciclización , Células HL-60 , Humanos , Estructura Molecular , Piranos/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , EstereoisomerismoRESUMEN
Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives.
Asunto(s)
Tecnología Química Verde/métodos , Piranos/química , Piranos/síntesis química , Alcoholes/química , Aldehídos/química , Ciclización , Dióxido de Silicio/química , EstereoisomerismoRESUMEN
The asymmetric synthesis of gymnastatin H has been achieved by using the photoisomerisation of a conjugated ester to its ß,γ-unsaturated isomer through the protonation of a in situ generated dienol as key step. Thanks to diacetone D-glucose used as a chiral alkoxy group, the protonation occurred well onto one of the two diastereotopic faces with very high yields and selectivities. Moreover, by this way the configuration of the C-6 centre of the target molecule was controlled.
RESUMEN
The first total synthesis of amphiasterin B4, a secondary metabolite previously isolated from Plakortis quasiamphiaster has been achieved. The core structure has been reached according to a highly stereoselective one-pot epoxidation/cyclization of an unsaturated diol. This substrate can be prepared from beta,gamma-unsaturated diesters readily available from the organocatalyzed protonation of a transient dienol generated by UV irradiation of corresponding alpha,beta-unsaturated isomers.
Asunto(s)
Furanos/síntesis química , Plakortis/química , Animales , Furanos/química , Estructura Molecular , Especificidad de la Especie , EstereoisomerismoRESUMEN
Chiral alpha- and beta-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic acid, (S)-mandelic acid, or (3R)-3-hydroxybutyric acid have been used as tether groups for intramolecular and diastereoselective [2 + 2] photocycloaddition of 3-oxocyclohexene carboxylic acid derivatives. Total regiocontrol toward the straight adduct and high diastereoselectivities (up to 94%) were observed in the case of butenyl lactate 11. After separation of the two diastereoisomers, cleavage of the chiral tether under basic conditions afforded cyclobutane lactones in good yield and enantiomeric pure form. An X-ray structure has been recorded that confirmed the relative and absolute configuration of the three contiguous stereogenic centers assigned according to CD spectra.