Total Synthesis of (±)‐Strictamine

The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all‐carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N‐dimethyl tertiary amine as a surrogate of the primary amine for the rapid build‐up of a functionalized 2‐azabicyclo[3,3,1]nonan‐9‐one skeleton (achieved by using a reaction sequence of α‐bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late‐stage construction of the indolenine unit.     

A Concise and Versatile Synthesis of Alkaloids from Kopsia tenuis: Total Synthesis of (±)‐Lundurine A and B

A total synthesis of (±)‐lundurines A and B is described. These natural products have a unique hexacyclic skeleton which includes a cyclopropane‐fused indoline. A stereospecific construction of the pentasubstituted cyclopropane core was achieved, by radical cyclization using SmI₂, with perfect stereoselectivity. Cyclizations to give seven‐ and five‐membered heterocycles, under palladium and ruthenium catalysis, respectively, accomplished the total syntheses. The late‐stage construction of the F ring by ring‐closing metathesis enabled access to the title compounds from a spiroindoline intermediate which is a common structure of other kopsia alkaloids.     

Total Synthesis of the Tetracyclic Antimalarial Alkaloid (±)‐Myrioneurinol

The first total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid (±)‐myrioneurinol has been accomplished using three highly diastereoselective reactions as pivotal steps: 1) an intramolecular Michael addition of a benzyloxycarbonyl‐protected lactam titanium enolate to an α,β‐unsaturated ester for construction of the spirocyclic C5 quaternary center and the a/d rings, 2) a malonate anion conjugate addition to a transient nitrosoalkene to install the requisite functionality and configuration at the C7 position, and 3) an intramolecular sulfonyliminium aza‐Sakurai reaction to form the b ring and the attendant C9/C10 configuration of the natural product.     

Total Synthesis of (±)‐Alstoscholarisine A

The first total synthesis of the neuroactive indole alkaloid (±)‐alstoscholarisine A is reported. The key step of the concise synthesis is an efficient domino sequence that was used to assemble the 2,8‐diazabicyclo[3.3.1]nonane core through the formation of two C?N bonds and one C?C bond in a single step.     

Enantioselective Total Synthesis of (−)‐Terengganensine A

A seven‐step enantioselective total synthesis of (?)‐terengganensine A, a complex heptacyclic monoterpene indole alkaloid, was accomplished. Key steps included: a) Noyori's catalytic enantioselective transfer hydrogenation of the iminium salt to set up the absolute configuration at the C21 position; b) a highly diastereoselective C7 benzoyloxylation with dibenzoyl peroxide under mild conditions; and c) an integrated one‐pot oxidative cleavage of cyclopentene/triple cyclization/hydrolysis sequence for the construction of the dioxa azaadamantane motif with complete control of four newly generated stereocenters.     

Total Synthesis of (±)‐Aspidophylline A

A total synthesis of aspidophylline A, a pentacyclic akuammiline‐type monoterpene indole alkaloid, is described. The synthesis features: 1) rapid access to a fully functionalized dihydrocarbazole through the desymmetrization of readily available 2‐allyl‐2‐(o‐nitrophenyl)cyclohexane‐1,3‐dione; 2) an intramolecular azidoalkoxylation of an enecarbamate to install both the furoindoline ring and the azido functionality; and 3) an intramolecular Michael addition for the construction of the 2‐azabicyclo[3.3.1]nonane ring system.     

Total Synthesis of (±)‐Integrifolin

The total synthesis of (±)‐integrifolin has been achieved for the first time through the stereoselective preparation of the bicyclo[5.3.0]decane skeleton based on the tungsten‐catalyzed cyclization of acyclic trienynes under photoirradiation conditions. Further key transformations of the cyclized product are the Tamao oxidation through cyclic silyl ether, the introduction of two oxygen functionalities by the oxidation of the diene and the construction of three exo‐methylene moieties.     

Total Synthesis of (+)‐Madangamine D

Madangamines are a group of bioactive marine sponge alkaloids, embodying an unprecedented diazapentacyclic skeletal type. The enantioselective total synthesis of madangamine D has been accomplished, and represents the first total synthesis of an alkaloid of the madangamine group. It involves the stereoselective construction of the diazatricyclic ABC core using a phenylglycinol‐derived lactam as the starting enantiomeric scaffold and the subsequent assembly of the peripheral macrocyclic rings. The synthesis provides, for the first time, a pure sample of madangamine D and confirms the absolute configuration of this alkaloid family.     

Collective Total Syntheses of Atisane‐Type Diterpenes and Atisine‐Type Diterpenoid Alkaloids: (±)‐Spiramilactone B, (±)‐Spiraminol, (±)‐Dihydroajaconine,and (±)‐Spiramines C and D

The first total syntheses of the architecturally complex atisane‐type diterpenes and biogenetically related atisine‐type diterpenoid alkaloids (±)‐spiramilactone B, (±)‐spiraminol, (±)‐dihydroajaconine, and (±)‐spiramines C and D are reported. Highlights of the synthesis include a late‐stage biomimetic transformation of spiramilactone B, a facile formal lactone migration from the pentacyclic skeleton of spiramilactone E, a highly efficient and diastereoselective 1,7‐enyne cycloisomerization to construct the functionalized tetracyclic atisane skeleton, and a tandem retro‐Diels–Alder/intramolecular Diels–Alder sequence to achieve the tricyclo[6.2.2.0] ring system.     

Total Synthesis of the Monoterpenoid Indole Alkaloid (±)‐Aspidophylline A

Aspidophylline A belongs to the akuammiline alkaloid family, the members of which possess intriguing cagelike structures and diverse biological activities. Herein we report a 15‐step synthesis of this alkaloid from conveniently available starting materials. The key elements of the synthesis include an intramolecular oxidative coupling to create the tetracyclic furoindoline motif of the natural product and a [Ni(cod)₂]‐mediated cyclization to install its piperidine ring.