Synthesis of Atisine,Ajaconine, Denudatine,and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine ( 2 , atisine type) and gymnandine ( 4 , denudatine type). The synthesis features a biogenetically inspired strategy that relies on C−H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization as key steps.     

Enantioselective Total Synthesis of Pseudopteroxazole and Ileabethoxazole

Enantioselective total syntheses of pseudopteroxazole ( 1 ) and ileabethoxazole ( 2 ) are presented. The two original stereocenters were constructed in excellent enantioselectivity and good diastereoselectivity through Carreira's asymmetric dual catalytic allylation, which shows potential for accessing diastereoisomers at C2 and C3 of 1 and 2 . Cationic cyclizations of 13 and 24 demonstrated an effective pathway for the construction of the opposite configurations at C1 in 1 and 2 . Additionally, an approach for the introduction of methyl at C4 is a feasible solution for structural modifications at C4 in 1 and 2 .     

One‐Step Multigram‐Scale Biomimetic Synthesis of Psiguadial B

A gram‐scale synthesis of psiguadial B, a purported inhibitor of human hepatoma cell growth, has been achieved in one step by a biomimetic three‐component coupling of caryophyllene, benzaldehyde, and diformylphloroglucinol. This cascade reaction is catalyzed by N,N′‐dimethylethylenediamine, and proceeds at ambient temperature to generate four stereocenters, two rings, one C−O bond, and three C−C bonds. Combined computational and experimental investigations suggest the biosynthesis of the natural product is non‐enzyme mediated, and is the result of a Michael addition between caryophyllene and a reactive ortho‐quinone methide, followed by two sequential intramolecular cationic cyclization events.     

Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

The novel tricyclic spiroketal alotane‐type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (−)‐alotaketals A–D and (−)‐phorbaketal A were accomplished [29–31 steps from (−)‐malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ‐keto‐alcohols to forge the common tricyclic spiroketal intermediate, 2) a late‐stage allylic C−H oxidation, and 3) olefin cross‐metathesis to install the different side chains.     

A Scalable Total Synthesis of the Antitumor Agents Et‐743 and Lurbinectedin

An efficient and scalable approach is described for the total synthesis of the marine natural product Et‐743 and its derivative lubinectedin, which are valuable antitumor compounds. The method delivers 1.6 % overall yield in 26 total steps from Cbz‐protected (S)‐tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light‐mediated remote C?H bond activation to assemble a benzo[1,3]dioxole‐containing intermediate.     

Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

A concise and enantioselective total synthesis of (+)‐jungermatrobrunin A ( 1 ), which features a unique bicyclo[3.2.1]octene ring skeleton with an unprecedented peroxide bridge, was accomplished in 13 steps by making use of a late‐stage visible‐light‐mediated Schenck ene reaction of (?)‐1α,6α‐diacetoxyjungermannenone C ( 2 ). Along the way, a UV‐light‐induced bicyclo[3.2.1]octene ring rearrangement afforded (+)‐12‐hydroxy‐1α,6α‐diacetoxy‐ent‐kaura‐9(11),16‐dien‐15‐one ( 4 ). These divergent photo‐induced skeletal rearrangements support a possible biogenetic relationship between (+)‐ 1 , (?)‐ 2 , and (+)‐ 4 .