Total Synthesis of (−)‐Vindorosine

Outlined herein is a novel and scalable synthesis of (−)‐vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone‐derived lithium dienolates with indolyl N ‐tert‐butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza‐Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (−)‐vindorosine and related alkaloids.     

Total Synthesis of (−)‐Merochlorin A

The first asymmetric total synthesis of the meroterpenoid (?)‐merochlorin A is described. The route features enantiospecific gold‐catalyzed tandem 1,3‐acyloxy migration/Nazarov/aldol reaction sequence to furnish the bicyclo[3.3.0]octane core in a single step from a linear propargylic 1,3‐enyne aldehyde. After completion of the central skeleton by reductive enol lactone rearrangement, late stage Diels–Alder cycloaddition/aromatization sequence installed the resorcinol. An additional salient feature of the synthesis is the assignment of the absolute configuration, which had not been determined previously.     

Total Synthesis of (−)‐Spiroleucettadine

One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans ‐fused 5,5‐bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (−)‐spiroleucettadine by a highly efficient biomimetic approach starting from l ‐tyrosine. One of two key hypervalent‐iodine‐mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure–biological‐activity relationships of these antibacterial compounds.     

A Concise Total Synthesis of (−)‐Himalensine A

The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (?)‐himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu‐catalyzed nitrile hydration, a Heck reaction to construct the challenging 2‐azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot‐economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency.     

Scalable Enantioselective Total Synthesis of (−)‐Goniomitine

A scalable enantioselective total synthesis of (?)‐goniomitine has been developed by using an iridium‐catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson–Claisen rearrangement, and one‐pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (?)‐goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)‐1,2‐dehydroaspidospermidine, (+)‐aspidospermidine, and (+)‐vincadifformine were also achieved.     

Organocatalytic,Asymmetric Total Synthesis of (−)‐Haliclonin A

The first total synthesis of the alkaloid (−)‐haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3‐alkenyl cyclohex‐2‐enone to set the stereochemistry of the all‐carbon quaternary stereogenic center. The synthesis also features a Pd‐promoted cyclization to form the 3‐azabicyclo[3,3,1]nonane core, a SmI₂‐mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring‐closing alkene and alkyne metathesis reactions to build the two aza‐macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.