Total synthesis of three eudesman-12,8-olides, (±)-isoalantolactone, (±)-dihydrocallitrisin and (±)-septuplinolide; structure revision of septuplinolide

Abstract

Four eudesman-I 2,8-olidesr ( f ) -isoalantolactone, () -septuplinolide and its epimeric eudesmanolide at C-4 were synthesized stereoselectively via the route involving alkylation annulation of 2-methyl-3-furoic acid and oxidation of the furan ring. It was found that the structure of septuplinolide is the C -4 epimer of the reported structure.) -dihydrocallitrisin, ( Recently, manifoldly oxygenated eudesmanolides have been isolated from different plant sources, and have been shown a wide range of biological activity, such as allergenic agent, plantgrowth inhibitor, antibacterial agent and antitumour agent activity.Previously, we reported syntheses of several furanoeremophilanes which are natural perhydronaphthofurans, uiu the coupling of two fragments A and B by alkylation of 2,4-dimethyl-3-furoic acid.* Eudesmanolides are also popular natural perhydronaphthofuran derivatives whose common carbon skeleton has methyl groups at different positions from those in the furanoeremophilanes. We intended to synthesize various eudesmanolides by a similar synthetic route which includes alkylation-annulation of 2-methyl-3-furoic acid 1 and oxidation of a furan ring to a y-lactone ring." The relative stereochemistry of the y-lactone ring with the 10-Me group of isoalantolactone 2 ' ' is opposite to that of dihydrocallitrisin 3."313 Septuplinolide was isolated by Ober and Fischer in 1987 and the structure was proposed to be a eudesmanolide with structure 4.14 In our survey of eudesmanolides, the oxygen function of C-4 of eudesmanolides is bonded on the 4a side,2-7.1 5 -19 except for a fewThe spectral data of the synthesized compound 4, which has the proposed structure for septuplinolide, were apparently different from the reported data of septuplinolide." The difference in the 'H NMR spectra between the two compounds suggested that the correct structure of septuplinolide is the C-4 epimer 5 of the reported structure 4 for septuplinolide. We report here the stereoselective syntheses of four eudesman-12,8-olides, ( f )isoalantolactone 2,' ' ( k )-dihydrocallitrisin 3,". ( +)-septuplinolide l4 5 and the C-4 epimeric (+)-eudesmanolide 4 of 5, and the spectroscopic structural elucidation of septuplinolide (Scheme 1).

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

“…The formate ester trapping approach, referred to earlier, was employed by Tada and co-workers in the synthesis of the eudesmanolide septuplinolide (66; Scheme 10). [59] The enolate of g-butyrolactone 64 was generated using sodium hydride and trapped with ethyl formate, and the resulting aldehyde was reduced to the a-(hydroxymethyl)-g-butyrolactone 65 with sodium borohydride. Without purification, alcohol 65 was treated with tosyl chloride and base to give septuplinolide (66) in 42 % yield over the 3 steps.…”

Constituents of two Flourensia species

“…The molecular formula of 1 was identical to that of septuplinolide (2) and both the IR profile and the 13 C NMR spectrum of compound 1 resembled those reported for septuplinolide (2) (Tada et al, 1993).…”

“…The structure of septuplinolide (2) was previously confirmed by stereoselective synthesis as a trans decaline with C-8 cis annelation (Tada et al, 1993) and single X-ray diffraction analysis (Vargas et al, 1991). The NOEs between H-14b/H-15b and H-7a/H-8a confirmed the relative stereochemistry.…”

“…The MeOH extract of the aerial parts of a collection of F. riparia from Salta province (Argentina) yielded: 4b-hydroxy-4,10a-dimethyl-7aH,8aH-eudesman-11-ene-8,12-olide (1); septuplinolide (2) (Tada et al, 1993); isoalantolactone (Bohlmann et al, 1978); carabrone (Yoshioka et al, 1973); encecalin (Bjeldanes and Geissman, 1969); 6-methoxytremetone (Castañeda et al, 1996); euparone (Elsohly et al, 1974) 2,5-diacetyl-6-methoxybenzofuran (Bin et al, 1997) and p-hydroxyacetophenone. Most of the flavonoids isolated from this species carried an isoprenyl moiety at C-8.…”

Die Renaissance der α‐Methylen‐γ‐butyrolactone: neue Syntheseansätze

“…Den bereits angesprochenen Ansatz mit Ameisensäureester als Abfangreagens nahmen Tada und Mitarbeiter für die Synthese des Eudesmanolids Septuplinolid ( 66 , Schema ) 59. Zunächst stellten sie mit Natriumhydrid das Enolat des γ‐Butyrolactons 64 her, das sie dann mit Ethylformiat abfingen.…”