RESUMEN
The asymmetric total syntheses of hedyosumin E aglycon, 7,10-epoxyhedyosminolide and ent-zedolactone A were realized, with the first two being achieved for the first time.
Asunto(s)
4-Butirolactona/análogos & derivados , Sesquiterpenos de Guayano/síntesis química , 4-Butirolactona/síntesis química , 4-Butirolactona/química , Catálisis , Cristalografía por Rayos X , Reacción de Cicloadición , Modelos Moleculares , Sesquiterpenos de Guayano/química , EstereoisomerismoRESUMEN
An organocatalytic formal [4 + 2] cycloaddition reaction has been realized that permits rapid access to a wide range of bicyclo[2.2.1]heptane-1-carboxylates in a highly enantioselective manner from simple starting materials under mild and operationally simple conditions.
RESUMEN
The first and asymmetric total synthesis of hedyosumins A, B, and C was accomplished in 13-14 steps from simple starting materials. The essential tools that allow us to access the tetracyclic skeleton include an organocatalytic [4 + 3] cycloaddition reaction, an intramolecular aldol condensation, and an intramolecular carboxymercuration/demercuration enabled lactonization. A CBS-catalyzed asymmetric reduction was employed to boost the ee of the synthetic natural products to an excellent level. This synthesis established the absolute configurations of hedyosumins A, B, and C.
Asunto(s)
Productos Biológicos/síntesis química , Medicamentos Herbarios Chinos/síntesis química , Magnoliopsida/química , Sesquiterpenos de Guayano/síntesis química , Aldehídos/química , Productos Biológicos/química , Catálisis , Cristalografía por Rayos X , Medicamentos Herbarios Chinos/química , Conformación Molecular , Estructura Molecular , Sesquiterpenos de Guayano/químicaRESUMEN
A pharmaceutical-oriented, transition-metal-free, cyanide-free one-step direct transformation of methylarenes to aryl nitriles is described. For the dimethylarenes, the selectivity can be well-controlled to form mononitriles or dinitriles. Enantioenriched nitriles can also be synthesized by this method. As a pharmaceutically practical method, the antidepressant drug citalopram was synthesized from cheap and commercially abundant m-xylene on a gram scale in high yield, avoiding transition-metal residues and toxic cyanides.
Asunto(s)
Citalopram/síntesis química , Nitrilos/síntesis química , Xilenos/química , Antidepresivos de Segunda Generación/síntesis química , Química Farmacéutica , EstereoisomerismoRESUMEN
The first synthetic attempt commencing from an eight-membered ring to approach the [5.3.1] bicyclic core of vinigrol has demonstrated the feasibility of using the conformational bias of the cyclooctane-ring system to realize highly diastereoselective reactions. The synthetic potential of the newly disclosed access to in/out isomerism may stimulate broader interests.
Asunto(s)
Compuestos Bicíclicos con Puentes/síntesis química , Química Orgánica/métodos , Diterpenos/síntesis química , Alquilación , Catálisis , Cristalografía por Rayos X , Diterpenos/química , Oxidación-Reducción , Paclitaxel/química , Paladio , EstereoisomerismoRESUMEN
Huperzine A, huperzine B, and huperzine U are congeners isolated from the Chinese herb Huperzia serrata (= Lycopodium serratum ) in minuscule amounts. The most efficient total synthesis of huperzine A, the first asymmetric total syntheses of huperzine B, and the first total synthesis of huperzine U have been achieved efficiently in overall yields of 17%, 10%, and 9%, respectively, each spanning 10-13 steps from (R)-pulegone. The featured steps include palladium-catalyzed Buchwald-Hartwig coupling and Heck cyclization reactions and an Ir-catalyzed olefin isomerization reaction. This work has established the absolute configurations of huperzine B and huperzine U and revealed that natural huperzine A, huperzine B, and huperzine U possess the same set of absolute stereochemistries, thus providing support for the potential role of huperzine B and huperzine U in the biosynthesis of huperzine A.
Asunto(s)
Alcaloides/síntesis química , Medicamentos Herbarios Chinos/síntesis química , Lycopodium/química , Monoterpenos/química , Sesquiterpenos/síntesis química , Alcaloides/química , Monoterpenos Ciclohexánicos , Medicamentos Herbarios Chinos/química , Estructura Molecular , Sesquiterpenos/química , EstereoisomerismoRESUMEN
The concise collective total synthesis of englerinâ A and B, orientalolâ E and F, and oxyphyllol has been accomplished in 10-15 steps, with the total synthesis of orientalolâ E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1)â the intramolecular Heck reaction to access the azulene core, 2)â the epoxidation-S(N)2' reduction sequence to access the allylic alcohol, 3)â the efficient regioselective and stereoselective formal hydration of the bridging C=C bond in the synthesis of englerins, and 4)â the late-stage chemo- and stereoselective C-H oxidation in the synthesis of orientalolâ E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalolâ E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Productos Biológicos/síntesis química , Carcinoma de Células Renales/química , Carcinoma de Células Renales/tratamiento farmacológico , Sesquiterpenos de Guayano/síntesis química , Antineoplásicos Fitogénicos/química , Productos Biológicos/química , Catálisis , Ciclización , Reacción de Cicloadición , Oxidación-Reducción , Sesquiterpenos de Guayano/química , EstereoisomerismoRESUMEN
An efficient total synthesis of (-)-epothilone B has been achieved in ca. 8% yield over 11 steps from 9 (or 10 steps from 7/8), which features a bissiloxane-tethered ring closing metathesis reaction to approach the trisubstituted (Z) double bond and forms a new basis for further development of an industrial process for epothilone B and ixabepilone.
Asunto(s)
Epotilonas/síntesis química , Ciclización , Epotilonas/química , Estructura Molecular , EstereoisomerismoRESUMEN
The total synthesis of Lycopodium alkaloid (-)-huperzine A has been accomplished in 10 steps with 17% overall yield from commercially abundant (R)-pulegone. The synthetic route features an efficient synthesis of 4 via a Buchwald-Hartwig coupling reaction, a dianion-mediated highly stereoselective alkylation of 4, and a rare example of an intramolecular Heck reaction of an enamine-type substrate. The stereoselective ß-elimination and the accompanying Wagner-Meerwein rearrangement are of particular interest.
Asunto(s)
Alcaloides/síntesis química , Monoterpenos/química , Sesquiterpenos/síntesis química , Alcaloides/química , Alquilación , Ciclización , Monoterpenos Ciclohexánicos , Lycopodium/química , Estructura Molecular , Sesquiterpenos/química , EstereoisomerismoRESUMEN
The first total synthesis of (-)-plicatic acid has been achieved by a concise and enantioselective route. In this synthesis, a conceptually new strategy featuring an asymmetric epoxidation-intramolecular epoxy-ring-opening Friedel-Crafts reaction sequence was developed for the stereoselective construction of the 2,7'-cyclolignane skeleton bearing contiguous quaternary-quaternary-tertiary stereocenters. The implementation of this strategy was enabled by the development of a modified protocol for the Seebach epoxidation with TADOOH, which affords an unprecedented, highly enantioselective and diastereoselective epoxidation with a range of alpha-carbonyl-beta-substituted acrylates 3.