(–)-Isosantonic acid: alteration of the hydrogen-bonding mode by configurational inversion at a single centre in a γ,∊-diketocarboxylic acid

Abstract

The title diketo acid, (1R,3aS,6aS,7R,9S)‐(−)‐α,3a,7‐tri­methyl‐5,8‐dioxo‐1,4‐ethano­perhydro­penta­lene‐1‐acetic acid (C15H20O4), is shown to aggregate in the crystal structure as acid‐to‐ketone hydrogen‐bonding catemers, whose chains follow 21 screw axes from each carboxyl to a ketone in a neighbouring mol­ecule [O⋯O = 2.7472 (13) Å and O⋯H—O = 172.7 (17)°]. Two parallel counterdirectional screw‐related single‐strand hydrogen‐bonding chains pass through the cell in the a direction. Six inter­molecular C—H⋯O=C close contacts are found. Comparisons are drawn with a diastereomer having the opposite configuration at the methyl­ated chiral centre adjacent to the carboxyl group.

Natural sesquiterpenoids

“…288 The structure of several compounds, such as (À)-parasantonic acid, (+)-parasantonide, (À)-isosantonic acid and (+)-santonide, which had been obtained from a-santonin, via santonic acid 332, have been confirmed by X-ray analysis. [289][290][291][292] Chlorahololide A 333 and chlorahololide B 334 are two dimeric lindenane derivatives, which have been isolated from Chloranthus holostegius. These sesquiterpenes were shown to be potent and selective blockers of the potassium channel.…”

(+)-Santonide, a sesquiterpenoid enol lactone derived from Artemisia

“…The structure of (I) ( Fig. 1) contains, either in evident or incipient form, all of the major structural features present in its hydrolysis product, (À)-isosantonic acid (Zinczuk et al, 2006). The stereochemistry at C7 in the latter compound is absent in (I) but arises during the hydrolysis.…”