Application of Photochemical Rearrangement of Santonin in Total Synthesis of Complex Natural Terpenoids

Abstract

Terpenoids represent one of the largest and most diverse classes of secondary metabolites and widely exist in nature. Among them, sesquiterpene lactones are ubiquitous in a variety of medicinal plants, which are the main active ingredients of many traditional Chinese herbal medicines. However, it is extremely challenging to accomplish the total synthesis of these natural compounds. Photochemical rearrangement of santonin is an effective strategy to construct the guaianolide skeleton. Furthermore, as a renewable natural resource, santonin was extensively used in natural product total synthesis, especially complex terpenoids. In this review, a brief overview of application of photochemical rearrangement of santonin in total synthesis of natural terpenoids is presented, which mainly includes: (1) the synthesis of sesquiterpene and its oligomers, and (2) the core structure construction of some diterpenoids.

Total Synthesis of (−)-Rhodomollanol A

“…We envisioned that (−)- 7 might be synthesized from pentacycle 8 through a late-stage core modification. Based on the findings from Matsumoto, Shiozaki and Hiraoka, and Carreira, the latter intermediate was hypothesized to be accessible from cyclohexa-dienone 10 through a photo-Nazarov cyclization , /intramolecular cycloetherification cascade via 9 to forge the 7-oxabicyclo­[4.2.1]­nonane ring of the molecule. For the construction of 10 , an unprecedented skeletal rearrangement of tetracycle 13 was devised.…”

Gram-Scale Synthesis of Bufospirostenin A by a Biomimetic Skeletal Rearrangement Approach

“…Because we were aware of the previously reported bioconversion of 2,5-cyclohexadienones to 5/7-fused enone products, we envisioned that compound 16 , which has the desired core framework, might be derived from dienone 14 through a 1,2-migration of C5 from C10 to C1 initiated by acid-induced enolization (Scheme A). The overall transformation from 14 to 16 is formally similar to the classical photochemical rearrangement of santonin (photosantonin rearrangement) . Deconjugation and reduction of 16 followed by desaturation would afford 4 via 19 .…”

“…The overall transformation from 14 to 16 is formally similar to the classical photochemical rearrangement of santonin (photosantonin rearrangement). 20 Deconjugation and reduction of 16 followed by desaturation would afford 4 via 19. Alternatively, we speculated that 19 could be generated directly from ruscogenin (17) by means of a Wagner−Meerwein rearrangement (Scheme 2B).…”

Total Synthesis of Laurane and Guaiane Sesquiterpenoids via Oxidative Nazarov Reaction

“…[ 1 ] The power of Nazarov cyclization has been demonstrated in many natural product syntheses. [ 2 ] Despite various impressive achievements in this field, such as ground‐state [ 1‐7 ] and excited‐state electrocyclization (including photo‐santonin rearrangement), [ 8‐9 ] it has not been successful in transforming unfunctionalized tertiary divinyl carbinols (TDCs) to their corresponding cyclopentenone derivatives. Currently, straightforward method for this purpose is lacking but is critical to expand the frontier of the Nazarov reaction.…”