RESUMEN
The catalytic asymmetric total syntheses of the biologically important and therapeutically valuable Amaryllidaceae alkaloids (-)-galanthamine and (-)-lycoramine have been divergently achieved from commercially available 3-butyn-1-ol. A newly developed spirocyclic pyrrolidine (SPD)-catalyzed enantioselective Robinson annulation rapidly constructs the key cis-hydrodibenzofuran core, which bears an all-carbon quaternary stereocenter of the target molecules with an excellent stereoselective control. Additionally, the current asymmetric synthetic strategy provides an alternative approach toward the syntheses of (-)-galanthamine and its analogues.
Asunto(s)
Alcaloides de Amaryllidaceae/síntesis química , Galantamina/síntesis química , Pirrolidinas/química , Compuestos de Espiro/química , Alcaloides de Amaryllidaceae/química , Catálisis , Galantamina/química , Estructura Molecular , EstereoisomerismoRESUMEN
The development of methods toward the construction of quaternary carbon centers has been a hot topic in recent years. In this work, an Au(I)-catalyzed intramolecular cyclization/semipinacol rearrangement of allene-containing allylic silyl ether was developed to provide a direct strategy for the construction of multisubstituted cyclohexene-type compounds with a quaternary carbon center in moderate to good yields. In particular, this method provides an alternative synthetic strategy for the construction of a multisubstituted spirocyclo[4.5]decane skeleton and may be applied to the synthesis of related bioactive molecules and their derivatives, thus facilitating the corresponding functional studies.
RESUMEN
(â)-Morphine, which is selected as an essential medicine by World Health Organization, is widely applied in the treatment of the pain-related diseases. Due to its synthetically challenging molecular architecture and important clinical role, extensive synthetic studies of morphine-type alkaloids have been conducted. However, catalytic asymmetric total synthesis of (â)-morphine remains a long-standing challenge. Here, we disclose an efficient enantioselective total synthesis of (â)-morphine in a longest linear sequence of 16 steps. The key transformation features a highly enantioselective Robinson annulation enabled by our spiro-pyrrolidine catalyst to rapidly construct the densely functionalized cis-hydrodibenzofuran framework containing vicinal stereocenters with an all-carbon quaternary center. This asymmetric approach provides an alternative strategy for the synthesis of (â)-morphine and its analogues.
Asunto(s)
Analgésicos Opioides/síntesis química , Morfina/síntesis química , Benzofuranos/síntesis química , Carbono , EstereoisomerismoRESUMEN
A facile and efficient method to form a chiral multi-substituted 3H-spiro[benzofuran-2,1'-cyclopentane] structural unit has been developed via a one-pot [3+2] cyclization/semipinacol rearrangement cascade. A catalysis system of Cu(ii)/BOX has been used to efficiently construct a key stereogenic center via a cyclization between substituted benzoquinones and allylic alcohols affording the desired products in good yields and with excellent enantioselectivities and diastereoselectivities (21 examples; up to 67% yields; up to 92% ee and up to >20 : 1 dr). This method provides an alternative strategy for the synthesis of the corresponding bioactive molecules containing spiro[benzofurancyclopentane] skeleton units.
RESUMEN
A Zn(OTf)2-promoted cyclization reaction of tosylhydrazones with 2-(dimethylamino)malononitrile has been successfully developed providing an efficient strategy for the synthesis of substituted 1-tosyl-1H-pyrazoles.