Total Synthesis of Panaginsene with Structural Revision

Abstract

A facile total synthesis of the reported structure for panaginsene through a trimethylenemethane (TMM) diyl mediated tandem cycloaddition reaction revealed that the spectroscopic data of the synthesized structure did not match with the data of the natural product. The total synthesis of the stereoisomer of the reported structure confirmed that the correct structure of panaginsene was the 11-epi stereoisomer of the originally proposed structure of panaginsene.

Total Synthesis of Panaginsene

“…The 1,5‐diketo precursor 4 was subjected to low‐valent Ti, generated in situ from TiCl 4 and Zn, successfully leading to the synthesis of panaginsene ( 1 ) in 70% yield. The spectral data of the product, except for optical rotation that was not reported, [1] were in good agreement with those of the isolated one as well as that synthesized by Lee [5] …”

“…Although biological activity of panaginsene was not reported, it has been isolated from a medicinal plant and it belongs to the senoxydane family of angularly fused triquinanes. Till date, senoxydene (3) is the only member of this family whose synthesis has been reported but actual structure is still unknown [4] and only one racemic total synthesis of panaginsene (1) has been reported by Lee group [5] in which the stereochemistry of the C11-Me group was corrected. Lee group used (trimethylenemethane)-diyl mediated intramolecular tandem [2 + 3] cycloaddition reaction to construct the challenging angularly fused quaternary carbon center.…”

“…The spectral data of the product, except for optical rotation that was not reported, [1] were in good agreement with those of the isolated one as well as that synthesized by Lee. [5] In conclusion, we have accomplished the total synthesis of panaginsene in 11 steps from enone 7. [19] The synthesis relied on key steps like conjugate addition reaction, Sharpless asymmetric epoxidation, Ti(III)-mediated reductive epoxide opening with radical cyclization to install the quaternary carbon stereocenter of the molecule.…”

Chromatography with silver nitrate: part 2

“…55 The crude target molecule (74), however, was found to contain a number of impurities, presenting a considerable purification challenge unassisted by its volatile and nonpolar nature. Panaginsene (74) was finally purified using SNIS (Scheme 8).…”

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.…”