Solid State Structure and Absolute Configuration of Filifolinol Acetate

Abstract

Careful reevaluation of the 1 H and 13 C NMR spectroscopic data of filifolinol acetate (4) led to the reassignment of the C-10 and C-11 signals, as well as the gem-dimethyl signals. Single crystal X-ray analysis provided an independent structural confirmation of 4, and comparison of the experimental vibrational circular dichroism spectrum with calculations performed using density functional theory provided the absolute configuration of this 3H-spiro-1-benzofuran-2,1'-cyclohexane and related molecules.

Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products

“…The absolute conguration of the revised structure (as depicted below) was determined using VCD and DFT (B3LYP/ DGDZVP) calculations for the diacetate derivative. 154 The absolute conguration of the algal meroditerpenoids (À)-taondiol diacetate (132) and (+)-epitaondiol diacetate (133) was determined by VCD and DFT calculations (B3LYP/DGDZVP and B3LYP/DGDZVP2, respectively). 148 The previous erroneous assignments were based on the ECD helicity rule for the chromane chromophore, 149 which was shown to be invalid for the title molecules aer theoretical calculations of ECD spectra.…”

Diastereoselective Synthesis of Spirodihydrobenzofuran Analogues of the Natural Product Filifolinol

“…[17] Thus, the so called steric approach control, a term coined by Dauben, [18] and further developed in the torsional strain model proposed by Fehlkin and Ahn, [19] would allow us to obtain the stereoisomer with the hydroxyl group in axial position as observed in the X-ray structure of Filifolinol Acetate. [20] Recently however, it has been shown that although the use of small nucleophiles tends to add to the axial face, some six-membered cyclic ketones suffered the hydride addition from the equatorial face even when a small hydride reagent such as sodium borohydride (NaBH 4 ) is used. [21] With this in mind, three bulky hydride reagents, -H, LiAlH(t-BuO) 3 and NaBH(OCOCH 3 ) 3 in order to favor the equatorial approach of the hydride to the carbonyl compound were used.…”

“…This structure was assigned using NMR and single crystal X-ray analysis, and its absolute configuration was determined as 2S,9S,12R using VCD and DFT (B3LYP/DGDZVP) calculations. [20] At late stage of the synthesis, examination of literature reports involving synthesis of spirodihydrobenzofurans, showed that only a few methodologies to carry out the key spiroannulation reaction have been reported. For example, in the total synthesis of K-76 ( Figure 3), a fungal metabolite isolated from Stachybotrys complementi nov. sp, [27] and one of the most widely used complement inhibitors, [10] the spirocyclization reaction was achieved using a THF-ethylene glycol-2.0 N hydrochloric acid mixture.…”

Progress in the Chemistry of Organic Natural Products 100

“…73 . One glycerol unit can be replaced by a branched nonitol (calditol) ( 314 ). These compounds can also be found in geological specimens ( 315 ).…”

“…The absolute configuration of filifolinol acetate (282) was determined by VCD methodology using DFT at the B3LYP/DGDZVP level of theory (314). The atomic coordinates from its X-ray structure were used as a starting point for the conformational search using the MMFF force field.…”