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The relative reactivity of three hydroxyl groups in aconitine toward acetylation, chlorination, sulfonylation, and oxidation has been studied in this paper. The reduction of C-3 ketone and C-15 ketone derivatives of aconitine was also investigated. It was found that (1) the relative reactivity of three hydroxyl groups toward acetylation, chlorination, and sulfonylation is 3-OH>13-OH>>15-OH; (2) 3-OH is much more reactive than 15-OH toward oxidation; and (3) reduction of the carbonyl group at C-3 with NaBH4 generated a pair of C-3 epimers, while the reduction products of the carbonyl group at C-15 depend largely on the specific reducing agent and the absolute configuration of 16-OCH3. When the substrate has 16β-OCH3, its carbonyl group at C-15 can be reduced with NaBH4 to yield exclusively the 15α-OH-containing product. Upon replacement of reducing agent NaBH4 with LiAlH4, the C-15 carbonyl group can be reduced to yield a pair of C-15 epimers. On the other hand, when the substrate has 16α-OCH3, C-15 carbonyl group can only be reduced to generate 15α-OH-containing product. [ABSTRACT FROM AUTHOR]

The O-acyl group at C-1 of two C19-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C19-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C19-diterpenoid alkaloids. [ABSTRACT FROM AUTHOR]

A series of new bisbenzylisoquinoline alkaloids was partially synthesized from tetrandrine and fangchinoline and evaluated for their ability to reverse P-glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test compounds increased the intracellular accumulation rate of rhodamine 123 in MDR cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity relative to the reference compound verapamil. Compounds 8, 10, 13, and 14 enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells. [ABSTRACT FROM AUTHOR]

The first biomimetic conversion from the aconitine-type C19-diterpenoid alkaloids to the corresponding alkaloids of lactone-type C19-diterpenoid alkaloid has been achieved. Chasmanine was used as starting material with Baeyer–Villiger oxidation as a key reaction. It was also observed that the oxygenated group at C-16 did not change the relative migration tendencies of C-13 and C-9 during the oxidation. Meantime, a novel D-ring fragmented compound was obtained during the course of the present investigation. The plausible mechanism of the formation of this compound was also proposed. [ABSTRACT FROM AUTHOR]

Four novel taxoid analogs were conversionally synthesized from the C19-diterpenoid alkaloid deltaline, and their cytotoxic activities were evaluated against a small panel of cancer cell lines. [ABSTRACT FROM AUTHOR]

The regioselective demethylations of two C19-diterpenoid alkaloids, 2 and 3, have been achieved with HBr-HOAc, trimethylsilyl iodide, or BBr3. It was observed that HBr-HOAc is an optimal demethylating agent for these two C19-diterpenoid alkaloids because it could provide different O-demethylation products by using different reaction temperature and reaction time. Especially, 1-O-methyl group in 2 and 3, one of the most difficult ones to be demethylated, could be removed by the treatment with HBr-HOAc at an elevated temperature and a prolonged reaction time. [ABSTRACT FROM AUTHOR]