Synthesis and Structure Confirmation of Selagibenzophenone C

Abstract

We report the first total synthesis of natural diarylbenzophenone selagibenzophenone C recently isolated from a plant species Selaginella tamariscina, traditionally used in folklore medicines. The framework of the natural compound is assembled via Suzuki‐Miyaura cross‐coupling and the addition of organometallic species. Following some ambiguities in the assignment of the structures for some of the natural products belonging to this compound class, the spectral data reported for the isolated selagibenzophenone C are carefully compared to the data of the synthetic product, and the structure of the natural product is confirmed.

The Biomimetic Synthesis of Polyarylated Fluorenes, Relevant to Selaginellaceae Polyphenols, Leading to the Spontaneous Formation of Stable Radicals

“…This alcohol was prepared in two steps from 2,4-dichlorobenzaldehyde ( 13) by Suzuki cross-coupling with 4-methoxyphenyl boronic acids to yield aldehyde 14 and the addition of 4-methoxyphenylmagnesium bromide (15). Such alcohol contains the framework of another representative of the selaginellacea polyphenols, namely selagibenzophenone C. [9,14] The treatment of alcohol 16 with an excess of boron tribromide provided corresponding arylated fluorene 17 in 70 % yield.…”

“…The structural curiosity and the biological activity of these metabolites attracted the attention of synthetic as well as medicinal chemists. We reported a formal synthesis of selaginpulvilins C and D, [12] as well as selagibenzophenones A–C, [13,14] and clarified structural ambiguities, related to selagibenzophenone B. We also developed several derivatives of selagibenzophenone A ( 5 ) and identified a compound with selective cytotoxicity toward the prostate cancer cell lines, with negligible toxicity toward the healthy cells [15] .…”

Synthesis of Selagibenzophenone A and Its Derivatives for Evaluation of Their Antiproliferative, RORγ Inverse Agonistic, and Antimicrobial Effect**

“…In 2020, Chen et al reported the isolation of selagibenzophenone C. [21] The reported therapeutic potential of Selaginella-derived plant products as well as their structural peculiarity sparked interest in the synthesis of these natural products and derivatives thereof. We have recently become interested in the chemistry of Selaginella constituents and reported the formal total synthesis of selaginpulvilins C and D. [22] Furthermore, we prepared selagibenzophenones A (4 aa), B (3), [23] and C [24] and demonstrated that the structure of selagibenzophenone B was incorrectly elucidated. The compound reported as selagibenzophenone B (3) [19] (or selaphenin A [20] ) was, in fact, selagibenzophenone A (4 aa).…”

“…We have recently become interested in the chemistry of Selaginella constituents and reported the formal total synthesis of selaginpulvilins C and D [22] . Furthermore, we prepared selagibenzophenones A ( 4 aa ), B ( 3 ), [23] and C [24] and demonstrated that the structure of selagibenzophenone B was incorrectly elucidated. The compound reported as selagibenzophenone B ( 3 ) [19] (or selaphenin A [20] ) was, in fact, selagibenzophenone A ( 4 aa ) [23] …”