Two New Triterpenoids from Gelsemium Elegans and Aglaia odorata

Eleganoside A (1) and odoratanone A (15), a triterpenoid trisaccharide glycoside and a nortriterpenoid, together with twelve known compounds (2–13) and a mixture of cerebrosides (14) were isolated from Gelsemium elegans and Aglaia odorata. Their structures were elucidated by extensive spectroscopic and spectrometric analysis. Eleganoside A (1) features a 3- O-α-L-rhamnopyranosyl (1→4)-β-D-glucopyranosyl (1→4)-β-D-glucopyranoside of a peculiar 3,16-dihydroxyl-lanosta-8,24-dien-26-oic acid triterpenoid skeleton, and odoratanone A (15) is a 29-norcycloartane-type triterpenoid bearing an unusual five-membered methyl acetal ring. Anti-acetylcholinesterase/butyrylcholinesterase (AChE/BChE) assay indicated that at 50 μM, ethyl caffeate (5) was promising as a dual inhibitor of AChE and BChE, and paeonol (3) and 24-hydroperoxy-24-vinylcholesterol (9) exhibited BChE-selective inhibition.

The Williams Synthesis of (-)-4-Hydroxydictyolactone

(-)-4-Hydroxydictyolactone 3, representative of the cyclononene xenicanes isolated from the Dictyotacae algae, readily isomerizes thermally to the more stable ( Z )- 6,7-isomer. Attempts to directly form this strained ring system appeared to be fraught with difficulty. David R. Williams of Indiana University envisoned (J. Am. Chem. Soc. 2009, 131, 9038) that use of Suzuki coupling might ameliorate some of the strain, since at the point of commitment to bond formation, the Pd center would be included in the forming ring. This analysis led specifically to the trans ether 1, as cyclization of the trans ether appeared likely to be more facile than would cyclization of the alternative cis diastereomer. The first challenge was the assembly of the array the four contiguous alkylated stereogenic centers of 1. To this end, the Z secondary ester 7 was prepared from the acetonide 4 , available from mannitol, and ( R )-(+)-citronellic acid, prepared by oxidation of the commercial aldehyde. Addition of 7 to LDA led to decomposition, but inverse addition of LDA to a mixture of the ester, TMSCl, and Et3 N smoothly delivered the ketene silyl acetal. On warming, Ireland-Claisen rearrangement of the ketene silyl acetal led to the acid 8 with remarkable diastereocontrol. The last alkylated stereogenic center of 1 was installed by reductive cyclization of the formate ester 9. Again, the cyclization proceeded with remarkable diastererocontrol. Although the intramolecular reaction of in situ prepared allyl metals is well precedented, the addition to a formate ester had not previously been reported. Although 11 appears to be ready for the long-awaited Suzuki coupling, in fact the TIPS protecting group substantially slowed hydroboration. The free alcohol/methyl acetal was the best substrate for hydroboration, but the free alcohol entered into other side reactions. After extensive experimentation, a happy medium was found with the methyl acetal/TBS ether 1. Selenylation of the lactone 12 followed by oxidative elimination of the selenide delivered the expected Z alkene. Removal of the silyl protecting group had to precede introduction of the second alkene, as the product 3 deteriorated rapidly on exposure to the alkaline conditions of TBAF cleavage.