Daphnepedunins A-F, Anti-HIV Macrocyclic Daphnane Orthoester Diterpenoids from Daphne pedunculata.

From the whole plant of Daphne pedunculata, 12 macrocyclic daphnane diterpenoids, including six new compounds, daphnepedunins A-F (1-4, 9, and 10), were isolated. Their structures were elucidated by physiochemical and spectroscopic data analysis, the modified Mosher's method, and X-ray crystallography. The isolated compounds were evaluated for anti-HIV activity against HIV-1 infection in MT4 cells and showed significant anti-HIV activity with IC50 values of 36.3-994 nM. A consideration of the anti-HIV activity of these compounds provided further insight into the structure-activity relationships of macrocyclic daphnane diterpenoids.

Selective Synthesis of the Aminobutadiene Intermediate and Mechanistic Analysis of 1,4-Dihydropyridine Formation Reaction in Water.

We previously isolated an aminobutadiene derivative as a by-product in the synthesis of a 1,4-dihydropyridine (1,4-DHP) derivative by the reaction of methyl propiolate with excess ammonium acetate in water, and we proposed that it is an intermediate in the formation of 1,4-DHP. Here, to test this idea and to investigate the reaction mechanism, we selectively synthesized the aminobutadiene derivative in EtOH and examined its reactivity. The yield of the aminobutadiene derivative was increased in the presence of excess ammonium salt. X-Ray crystal structure analysis indicated the presence of an intramolecular hydrogen bond between the terminal amine and ester carbonyl oxygen, together with a short C-N bond length consistent with enamine-imine equilibrium. Direct cyclization of the aminobutadiene derivative with methyl propiolate to afford the 1,4-DHP derivative did not proceed well, but the yield was increased in the presence of morpholine salt as an additive. These results suggest that the predominant reaction pathway from the intermediate to 1,4-DHP in water involves Michael addition of a second amine molecule and reaction with methyl propiolate, followed by intramolecular cyclization and elimination of amine.

Cylindrical macrocyclic compounds synthesized by connecting two bowl-shaped calix[3]aramide moieties: structures and chiroptical properties.

Calix[3]aramide-based macrocycles 1 were successfully synthesized by a Glaser coupling reaction of two meta-calix[3]aramide moieties that have three ethynyl groups. The obtained macrocycles have stereoisomers: an enantiomeric pair and a meso form based on a combination of amide bond directions in the calix[3]aramide moieties at both ends of the molecule. Characteristic absorption spectra derived from the 1,4-diphenylbutadiyne structure were observed, while their ECD spectra were mirror-images. Single-crystal X-ray analysis revealed that each stereoisomer had a cylindrical rigid shape, and the absolute structure of the chiral-form was also assigned by comparing the Flack parameters. Mirror-image VCD spectra were observed for the enantiomeric chiral forms, and a VCD signal pattern of one enantiomer corresponded to that predicted by the relationship between the dihedral angle of the pair of C[double bond, length as m-dash]O groups.

Synthesis and chiroptical properties of cylindrical macrocycles comprising two calix[3]aramide moieties.

Calix[3]aramide-based cylindrical macrocycles were synthesized by the one-step amide coupling reaction of a monomer containing two meta-alkylaminobenzoic acid units linked by para-phenylene bridges. The major products included a meso-form and an enantiomeric pair, with stereochemistry derived from the direction of the amide bonds and their fixed conformation. Mirror-image ECD, VCD, and CPL spectra were observed in the enantiomeric pair and the absolute structure was determined by comparing measured and calculated ECD and VCD spectra.