Covering: January 2013 to September 2018Sulfur-containing natural products are a large class of significant functional molecules. Many of these compounds exhibit potent biological activities and ...pharmacological properties; in fact, some of them have been developed into important drugs. The total synthesis of sulfur-containing natural products is a subject that has long attracted significant attention from synthetic organic chemists; to achieve this goal, various methods have been developed over the past years. This review surveys total syntheses of sulfur-containing natural products that introduce sulfur atoms using different sulfurization agents to construct related sulfur-containing moieties.
A uniformly strategic total synthesis of Aspidosperma alkaloids (+)-vincadifformine, (−)-quebrachamine, (+)-aspidospermidine, (−)-aspidospermine, (−)-pyrifolidine, and nine others from efficiently ...constructed tricyclic ketone 13 is reported. Highlights of these divergent and practical syntheses include (i) stereoselective intermolecular 4 + 2 cycloaddition to establish a C–E ring with one all-carbon quaternary stereocenter (C-5) and two bridged contiguous cis-stereocenters (C-12 and C-19), (ii) a Pd/C-catalyzed hydrogenation/deprotection/amidation cascade process to assemble the D ring, and (iii) Fischer indolization to forge the A–B ring.
A palladium‐catalyzed regiodivergent C1 insertion multicomponent reaction involving aryne, CO, and 2‐iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. ...Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand‐free condition. In comparison, application of the electron‐abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method.
Divergent alkaloid synthesis: A multicomponent, regioselective approach for palladium‐catalyzed C1 insertion is described. This reaction was applied in the divergent synthesis of phenanthridinone and acridone natural product core scaffolds.
A concise and stereocontrolled strategy for the syntheses of oxygenated Aspidosperma and Vinca alkaloids, via a stereoselective intermolecular inverse-electron-demand 4 + 2 cycloaddition, a ...challenging α,β-unsaturated ketone indolization rearrangement with excellent regio- and stereoselectivity, and an efficient Pd/C-catalyzed one-pot cascade reaction. The strategy has been demonstrated by the efficient asymmetric syntheses of antitumor drug (+)-vinblastine and five other oxygenated Aspidosperma alkaloids.
A highly diastereo- and enantioselective phosphine-catalyzed sequential 3 + 2/3 + 2 annulation of allenoates with arylidenemalononitriles has been developed. This reaction allows for the facile ...construction of multifunctionalized cis-fused bicyclic3,3,0octene scaffolds, encompassing three consecutive stereogenic centers with one quaternary carbon center, in a one-step operation from readily available materials. The reported protocol is scalable, operates under mild reaction conditions, and creates the core structural motif of a number of natural products.
Abstract
A palladium‐catalyzed regiodivergent C
1
insertion multicomponent reaction involving aryne, CO, and 2‐iodoaniline is established to construct the scaffolds of phenanthridinone and acridone ...alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand‐free condition. In comparison, application of the electron‐abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method.
An Fe-catalyzed 2-deoxy glycosylation method was developed from 3,4-O-carbonate glycals directly at room temperature. This novel approach enabled facile access to alkyl and aryl 2-deoxy glycosides in ...high yields with exclusive α-stereoselectivity, tolerating various alcohols, phenols, and glycals. The synthetic utility and advantage of this strategy have been demonstrated by the modification of six natural products and the construction of a tetrasaccharide.
S-Glycosides are more resistant to enzymatic and chemical hydrolysis and exhibit higher metabolic stability than common O-glycosides, demonstrating their widespread application in biological research ...and drug development. In particular, β-S-glycosides are used as antirheumatic, anticancer, and antidiabetic drugs in clinical practice. However, the stereoselective synthesis of β-S-glycosides is still highly challenging. Herein, we report an effective β-S-glycosylation using 3-O-trichloroacetimidoyl glycal and thiols under mild conditions. The C3-imidate is designed to guide Pd to form a complex with glucal from the upper face, followed by Pd–S (thiols) coordination to realize β-stereoselectivity. This method demonstrates excellent compatibility with a broad scope of various thiol acceptors and glycal donors with yields up to 87% and a β/α ratio of up to 20:1. The present β-S-glycosylation strategy is used for late-stage functionalization of drugs/natural products such as estrone, zingerone, and thymol. Overall, this novel and simple operation approach provides a general and practical strategy for the construction of β-thioglycosides, which holds high potential in drug discovery and development.
