Total Syntheses of (+)‐Grandilodine C and (+)‐Lapidilectine B and Determination of their Absolute Stereochemistry

Enantioselective total syntheses of the Kopsia alkaloids (+)‐grandilodine C and (+)‐lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)‐grandilodine C was achieved by palladium‐catalyzed intramolecular allylic amination and ring‐closing metathesis to give 8‐ and 5‐membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)‐lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.     

Total Synthesis of (+)‐MPC1001B

The first total synthesis of an epidithiodiketopiperazine alkaloid, (+)‐MPC1001B, was accomplished. This synthesis features a tetra‐n‐butylammonium fluoride mediated intramolecular aldol reaction for forming the 15‐membered macrolactone ring, and the construction of an epidithiodiketopiperazine substructure through a stepwise sulfenylation reaction involving a novel trityl trisulfide (TrSSS)‐group transfer.     

Asymmetric Total Synthesis of (−)‐Kravanhin B

The first asymmetric total synthesis of kravanhin B has been accomplished with a linear reaction sequence of 13 steps starting from (R)‐(?)‐carvone. The synthesis features an intramolecular aldol cyclization to construct the desired cis‐fused decalin skeleton and an acid‐catalyzed dehydration and olefin isomerization to install the γ‐butenolide ring.     

Enantioselective Total Synthesis of (−)‐Lansai B and (+)‐Nocardioazines A and B

The concise total syntheses of the bis(pyrroloindolines) (?)‐lansai B and (+)‐ nocardioazines A and B are reported. The key pyrroloindoline building blocks are rapidly prepared by enantioselective formal [3+2] cycloaddition reactions. The macrocycle of (+)‐nocardioazine A is constructed by an unusual intramolecular diketopiperazine formation.     

Expedient Synthesis of (+)‐Lycopalhine A

Two amino acids play a key role in the first total synthesis of lycopalhine A. l ‐glutamic acid serves as a convenient chiral starting material for the 13‐step synthesis, and l ‐proline promotes an unusual 5‐endo‐trig Mannich cyclization that generates the central pyrrolidine ring of the Lycopodium alkaloid. The bicyclo[3.3.0]octanol moiety of the molecule is formed through an intramolecular aldol addition that may occur spontaneously in nature.     

Total Synthesis of (−)‐Caprazamycin A

Caprazamycin A has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features a) the scalable preparation of the syn‐β‐hydroxy amino acid with a thiourea‐catalyzed diastereoselective aldol reaction, b) construction of a diazepanone with an unstable fatty‐acid side chain, and c) global deprotection with hydrogenation. This report provides a route for the synthesis of related liponucleoside antibiotics with fatty‐acid side chains.     

Total Syntheses of (−)‐Huperzine Q and (+)‐Lycopladines B and C

Utilizing a late‐stage enamine bromofunctionalization strategy, the twelve‐step total synthesis of (?)‐huperzine Q was accomplished. Furthermore, the first total syntheses of (+)‐lycopladines B and C are described. An unprecedented X‐ray crystal structure of an unusual epoxyamine intermediate is also reported, and the synthetic application of this intermediate in natural product synthesis is demonstrated.     

Total Synthesis of Leucosceptroids A and B

Leucosceptroids A and B are sesterterpenoids with potent antifeedant and antifungal activities. A more efficient gram‐scale total synthesis of leucosceptroid B and the first total synthesis of leucosceptroid A are presented. The key transformations include an aldol reaction between a substituted dihydrofuranone and an (S)‐citronellal‐derived aldehyde, a SmI₂‐mediated intramolecular ketyl–olefin radical cyclization, and final‐stage alcohol oxidation.     

10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D

The asymmetric synthesis of dragmacidin D ( 1 ) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C₂‐symmetric tetramine and lithium N‐(trimethylsilyl)‐tert‐butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6′′′ position, which is consistent with other members of the dragmacidin family of natural products.     

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.     

Bioinspired Total Syntheses of Isospongian‐type Diterpenoids (−)‐Kravanhins A and C

The first bioinspired total syntheses of (?) kravanhins A and C were accomplished from a labdane diterpenoid derivative. The key reactions involve a photooxidation and a one‐pot sequential aldol cyclization and lactonization, which provide a new plausible biosynthetic pathway for the kravanhins and other symbiotic members.     

A General Entry to Antifeedant Sesterterpenoids: Total Synthesis of (+)‐Norleucosceptroid A, (−)‐Norleucosceptroid B,and (−)‐Leucosceptroid K

The first asymmetric total synthesis of the antifeedant terpenoids (+)‐norleucosceptroid A, (?)‐norleucosceptroid B, and (?)‐leucosceptroid K has been accomplished. This highly concise synthetic route was guided by our efforts to develop a platform for the collective synthesis of a whole family of antifeedant natural products. The synthesis features a Hauser–Kraus‐type annulation followed by an unprecedented, highly efficient intramolecular dilactol aldol‐type condensation reaction to produce the 5,6,5 skeleton. The developed synthetic route proceeds for norleucosceptroid A and B in 16 steps (longest linear sequence) from known compounds.