Concise Syntheses of bis‐Strychnos Alkaloids (−)‐Sungucine, (−)‐Isosungucine,and (−)‐Strychnogucine B from (−)‐Strychnine

The first chemical syntheses of complex, bis‐Strychnos alkaloids (?)‐sungucine ( 1 ), (?)‐isosungucine ( 2 ), and (?)‐strychnogucine B ( 3 ) from (?)‐strychnine ( 4 ) is reported. Key steps included (1) the Polonovski–Potier activation of strychnine N‐oxide; (2) a biomimetic Mannich coupling to forge the signature C23?C5′ bond that joins two monoterpene indole monomers; and (3) a sequential HBr/NaBH₃CN‐mediated reduction to fashion the ethylidene moieties in 1 – 3 . DFT calculations were employed to rationalize the regiochemical course of reactions involving strychnine congeners.     

Total Syntheses of (−)‐Conidiogenone B, (−)‐Conidiogenone,and (−)‐Conidiogenol

Cyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6–8 consecutive stereocenters. The concise total syntheses of (?)‐conidiogenone B, (?)‐conidiogenone, and (?)‐conidiogenol have been accomplished in 14–17 steps. The present work features a HAT‐mediated alkene–nitrile cyclization to access the cis‐biquinane, a Nicholas/Pauson–Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton.     

Synthesis of (±)‐Nephromopsinic, (−)‐Phaseolinic,and (−)‐Dihydropertusaric Acids

The formal syntheses of (±)‐nephromopsinic acid, (−)‐phaseolinic acid, and the first total synthesis of (−)‐dihydropertusaric acid from (±)‐ and (−)‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one are described. These syntheses take advantage of a previously reported radical rearrangement (1,2‐acyl migration). A remarkable iodide‐mediated cleavage of a bicyclic system, followed by the introduction of the γ‐chains via a mixed Kolbe electrolysis, are the key steps of these syntheses. This approach is general and could be applied for the preparation of all kinds of paraconic acids with excellent control of the stereochemistry.     

Divergent Total Syntheses of Enmein‐Type Natural Products: (−)‐Enmein, (−)‐Isodocarpin,and (−)‐Sculponin R

Divergent total syntheses of the enmein‐type natural products (?)‐enmein, (?)‐isodocarpin, and (?)‐sculponin R have been achieved in a concise fashion. Key features of the strategy include 1) an efficient early‐stage cage formation to control succeeding diastereoselectivity, 2) a one‐pot acylation/akylation/lactonization to construct the C‐ring and C8 quarternary center, 3) a reductive alkenylation approach to construct the enmain D/E rings and 4) a flexible route to allow divergent syntheses of three natural products.     

Divergent Total Syntheses of Enmein‐Type Natural Products: (−)‐Enmein, (−)‐Isodocarpin,and (−)‐Sculponin R

Divergent total syntheses of the enmein‐type natural products (−)‐enmein, (−)‐isodocarpin, and (−)‐sculponin R have been achieved in a concise fashion. Key features of the strategy include 1) an efficient early‐stage cage formation to control succeeding diastereoselectivity, 2) a one‐pot acylation/akylation/lactonization to construct the C‐ring and C8 quarternary center, 3) a reductive alkenylation approach to construct the enmain D/E rings and 4) a flexible route to allow divergent syntheses of three natural products.     

Total Syntheses of (−)‐Isoschizogamine and (−)‐2‐Hydroxyisoschizogamine

Total syntheses of (?)‐isoschizogamine and (?)‐2‐hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine‐type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine‐type intermediate in the absence of oxygen provides natural (?)‐isoschizogamine. Conducting the reaction in the presence of oxygen leads to a multistep oxidative hydrolysis cascade that affords unnatural (?)‐2‐hydroxyisoschizogamine.     

Organocatalytic Asymmetric Mannich Cyclization of Hydroxylactams with Acetals: Total Syntheses of (−)‐Epilupinine, (−)‐Tashiromine,and (−)‐Trachelanthamidine

An asymmetric, organocatalytic, one‐pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89 % yield and 97 % ee. The total syntheses of (?)‐epilupinine, (?)‐tashiromine, and (?)‐trachelanthamidine also achieved to demonstrate the generality of the process.     

Organocatalytic Asymmetric Mannich Cyclization of Hydroxylactams with Acetals: Total Syntheses of (−)‐Epilupinine, (−)‐Tashiromine,and (−)‐Trachelanthamidine

An asymmetric, organocatalytic, one‐pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89 % yield and 97 % ee. The total syntheses of (−)‐epilupinine, (−)‐tashiromine, and (−)‐trachelanthamidine also achieved to demonstrate the generality of the process.     

Catalytic Asymmetric Total Synthesis of (−)‐Galanthamine and (−)‐Lycoramine

The catalytic asymmetric total syntheses of (?)‐galanthamine ( 1 ) and (?)‐lycoramine ( 2 ) have been achieved by using a conceptually new strategy featuring two metal‐catalyzed reactions as the key steps. A new method for the construction of 3,4‐fused benzofurans has been developed through a palladium‐catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2 . To achieve the asymmetric synthesis of 1 and 2 , a Sc^III/N,N′‐dioxide complex was used to catalyze the enantioselective conjugate addition of 3‐alkyl‐substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center.     

Gram‐Scale Synthesis of the (−)‐Sparteine Surrogate and (−)‐Sparteine

An 8‐step, gram‐scale synthesis of the (?)‐sparteine surrogate (22 % yield, with just 3 chromatographic purifications) and a 10‐step, gram‐scale synthesis of (?)‐sparteine (31 % yield) are reported. Both syntheses proceed with complete diastereocontrol and allow access to either antipode. Since the syntheses do not rely on natural product extraction, our work addresses long‐term supply issues relating to these widely used chiral ligands.     

Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline

(?)‐Daphnilongeranin B and (?)‐daphenylline are two hexacyclic Daphniphyllum alkaloids, each containing a complex cagelike backbone. Described herein are the first asymmetric total synthesis of (?)‐daphnilongeranin B and a bioinspired synthesis of (?)‐daphenylline with an unusual E ring embedded in a cagelike framework. The key features include an intermolecular [3+2] cycloaddition, a late‐stage aldol cyclization to install the F ring of daphnilongeranin B, and a bioinspired cationic rearrangement leading to the tetrasubstituted benzene ring of daphenylline.