Paratchata Batsomboon

Morusalisin A is a nonclassical mulberry Diels-Alder-type adduct (MDAA) with a unique tricyclic skeleton. Herein, we report the first total synthesis of morusalisin A, accomplished in nine steps with an overall yield of 7.3% from commercially available 2,4,6-trihydroxybenzaldehyde. A key feature of the synthesis is a stereoselective intramolecular Diels-Alder (IMDA) reaction of the benzo-tethered butadienyl cinnamate, which efficiently constructs the tricyclic tetrahydro-6H-benzo[c]chromen-6-one core bearing three contiguous stereogenic centers. The pivotal point of the transformation was the strategic placement of a protecting group ortho on the diene moiety, which not only accommodated the IMDA but also controlled the stereochemical outcome. This study is expected to pave the way for broader application of the IMDA strategies in the synthesis of MDAAs, which have predominantly been accessed through intermolecular DA reactions.

Six previously undescribed alkaloids, including three dimeric aporphine alkaloids, mitrephorines A-C (1-3), two aristolactam-aporphine alkaloids, mitrephorines D and E (4 and 5), and one 4,5-dioxoaporphine alkaloid, 8-methoxycepharadione A (6), accompanied by 13 previously identified compounds, were isolated from the bark of Mitrephora tomentosa. Their structures were determined by the analysis of UV, IR, NMR, and HRMS, while absolute configurations were assigned by chiral HPLC, specific rotation values, and ECD spectral data. Known compounds (7-19) were identified by comparison with literature data. The structure of mitrephorine A was verified by the analysis of single-crystal X-ray diffraction. Alkaloid dimers were isolated as mixtures of enantiomers (1-3) and atropisomers (4 and 5). Several isolates were evaluated against HuCCA-1, MOLT-3, HeLa, HepG2, T47-D, MDA-MB-231, S102, H69AR, HL-60, and A549 cancer cell lines, as well as the MRC-5 normal cell line. Compound 11 was active against MOLT-3 and HeLa cancer cell lines with respective IC₅₀ values of 4.5 and 5.1 μM, while compound 12 exhibited cytotoxicity against HuCCA-1 and MOLT-3 cancer cell lines (IC₅₀ values of 10.0 and 7.9 μM, respectively). None of the isolates were toxic against the MRC-5 normal cell line, with doxorubicin hydrochloride serving as the positive control.

A comprehensive phytochemical investigation of Artocarpus integer root extract led to the isolation of two new geranylated xanthones (1 and 2), one new geranylated flavone (3), one new flavanone (4), and one unique benzopyran (5), along with 16 known compounds. Structures of the new compounds were elucidated by a combination of spectroscopic and computational methods. Two different types of compounds, flavone 12 and arylbenzofuran 19, displayed the most potent antityrosinase activity with IC₅₀ values of 1.7 ± 0.2 and 1.2 ± 0.1 μM, respectively. In addition, kinetic measurements and molecular docking simulations of compounds 12 and 19 were performed and revealed that compound 12 is a competitive inhibitor binding with the tyrosinase active site, while compound 19 is a noncompetitive tyrosinase inhibitor binding the enzyme at the allosteric site.

Lysiphyllum binatum (Blanco) de Wit in the Fabaceae family, despite its traditional medicinal uses, has not been the subject of prior scientific inquiry in

A series of aporphines conjugated with an N-benzylpyridinium moiety through an amide-bond linkage were synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity. The conjugation of the N-benzylpyridinium group significantly enhanced the AChE inhibitory activity of the core aporphine. The halogen substituents on the benzyl group affected the activity of the conjugates. Both (S)- and (R)-enantiomers of three conjugates with low IC₅₀ values were synthesized and evaluated for their activities. All (S)-enantiomers exhibited higher activity than the corresponding (R)-enantiomers. The (S)-enantiomer of 2-chlorobenzylpyridinium-containing aporphine was the most potent inhibitor in this study with an IC₅₀ value of 0.06 ± 0.003 μM. Molecular dynamics simulation analysis revealed that both enantiomers can interact with the AChE binding site, whereas the (S)-enantiomer possessed slightly stronger interaction than the (R)-enantiomer, presumably because of their different orientations, as evidenced by molecular docking. The N-benzylpyridinium dehydroaporphine conjugates were also synthesized but were less active than the corresponding aporphine conjugates.

ortho-Quinone methides (o-QMs) underwent formal [4 + 2]-cycloaddition reactions with arylallenes regioselectively at the styrenyl olefin to furnish the corresponding 3-methylene-2-arylchromans in moderate to good yields (up to 88%). When R ≠ H, the reactions also proceeded with moderate stereoselectivity (up to 5:1) which was governed by the nature of the R group. The 3-methylene-2-arylchromans could serve as common intermediates for further functionalization including epoxidation, oxidative cleavage/Baeyer-Villiger oxidation, Riley oxidation, acid-catalyzed rearrangement, and Pd-catalyzed cross-coupling reactions to furnish the corresponding derivatives in moderate to good yields.

A convergent 5-step synthesis (LLS) of illudalic acid allows for concise preparation of analogues for pharmacological evaluation.