Total Syntheses of (+)‐Sarcophytin, (+)‐Chatancin, (−)‐3‐Oxochatancin, and (−)‐Pavidolide B: A Divergent Approach

Abstract

Ac oncise and divergent approach for the total syntheses of four cembrane diterpenoids,namely (+ +)-sarcophytin, (+ +)-chatancin, (À)-3-oxochatancin, and (À)-pavidolide B, has been developed, and it also led to the structural revision of (À)-isosarcophytin. The key steps of the strategy feature ad ouble Mukaiyama Michael addition/elimination, aHelquist annulation, two substrate-controlled facial-selective hydrations,a nd ap inacol rearrangement. The described syntheses not only achieved these natural products in an efficient manner,but also provided insight into the biosynthetic relationship between the two different skeletons.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…They were successfully used for the total synthesis of natural products, which included Brasilicardins A and C, (+)‐Frondosin A, (+)‐Tanikolide, Lundurines A−C, Onoseriolid, Isobolivianine, (−)‐Crinipellin A, Panaginsene, Echinopines, (+)‐ and (−)‐Isolaurepan, (−)‐Strychnofoline, (−)‐Clovan‐2,9‐dione, (+)‐Sarcophytin, [2 ° ] (+)‐Chatancin, [2 ° ] (−)‐3‐Oxochatancin, [2 ° ] (+)‐Cyperolone . In these cases, TsNHNH 2 reacted with aldehydes (or ketones) to form hydrazones that underwent cycloaddition or reduction subsequently. Banford‐Stevens reaction and Shapiro reaction were reported in this decade.…”

Total Synthesis of (−)-Pavidolide B: A Ring Contraction Strategy

“…2c Initial studies indicate that it can inhibit both PAF induced platelet aggregation and PAF receptor binding with IC 50 values of 0.22 μM and 0.32 μM, respectively, but has no effect on collagen, adenosine diphosphate, or arachidonic acid induced platelet aggregation. The above polycyclic cembranoids contain a common [6,6,6] tricyclic core structure, possessing six or seven stereogenic centers. In particular, the cis-decalin motif (A/B rings) is folded into a highly congested polycyclic arrangement via a transannularly bridged hemiketal between a tertiary alcohol at C10 and a ketone at either C3 or C14 position.…”

“…4 Preliminary investigations revealed that (−)-4 exhibits high selective inhibition against the human promyelocytic leukemia cell line HL-60 with an IC 50 of 2.7 μg/mL. Structurally, (−)-4 contains a challenging [6,5,5,7] tetracyclic ring system embedded within fully functionalized cyclopentane and seven contiguous stereogenic centers. In 2017, Yang, Gong, and coworkers disclosed an enantioselective total synthesis of (−)-4 by employing a cascade radical annulation of vinylcyclopropane as the key step.…”

“…5 Very recently, we also developed a divergent approach for the concise and efficient syntheses of four cembrane diterpenoids, including (+)-sarcophytin (1), (+)-chatancin (2), (−)-3-oxochatancin (3), and (−)-pavidolide B (4). 6 In continuation of our interest in this area, we herein describe an alternative total synthesis of (−)-4 through a ring contraction strategy.…”

“…We rationalized that (−)-pavidolide B (4) could be synthesized from acid 5 through a late-stage functionalization, involving a lactonization, a site-selective allylic oxidation 7 at C10, and epimerization at C11. For the construction of 5, a Wolff rearrangement 8 induced ring contraction of α-diazoketone 6 was projected as the means to assemble the [6,5,7] tricyclic carbon framework of the molecule. We expected the latter intermediate would be accessible from bicyclic diene 7 through a ring-closing metathesis (RCM).…”