Miwa Kubo

Novel Pentacyclic seco-Prezizaane-Type Sesquiterpenoids with Neurotrophic Properties from Illicium jiadifengpi

Three novel seco-prezizaane-type sesquiterpenoids, jiadifenolide (1), jiadifenoxolane A (2), and jiadifenoxolane B (3), were isolated from the pericarps of Illicium jiadifengpi. Their pentacyclic cage structures were determined by 2D-NMR methods, chemical conversion, and single-crystal X-ray analysis. Compounds 1 and 2 strongly promote neurite outgrowth in primary cultured rat cortical neurons at concentrations ranging from 0.01 to 10 muM.

Nerve growth factor-potentiating benzofuran derivatives from the medicinal fungus Phellinus ribis.

Four new benzofuran derivatives, ribisin A (1), ribisin B (2), ribisin C (3), and ribisin D (4), were isolated from the MeOH extract of the fruiting bodies of Phellinus ribis. Their structures including their absolute configurations were determined by NMR and CD exciton chirality methods. Compounds 1-4 were found to promote neurite outgrowth in NGF-mediated PC12 cells at concentrations ranging from 1 to 30 μM. The structure-activity relationships of these compounds are also discussed.

Chemistry and biological activities of Vibsane-type diterpenoids

This review focuses on the structural diversity, biological activities and synthesis of vibsane-type diterpenoids. Vibsane-type diterpenoids are considered to be rarely occurring natural products because they have been found exclusively in a few Viburnum species such as V. awabuki, V. odoratissimum, and V. suspensum. These diterpenoids are further classified into 11-membered ring, 7-membered ring, and rearranged (neovibsanin) types, and therefore, their chemical diversity forms a unique chemical library. We describe the absolute stereochemistry of the typical 11-membered ring vibsanins B and F, a variety of vibsane-type diterpenoids, the chemical correlations between the three subtypes, their biological activities, and the synthesis of vibsanin F and neovibsanin B.

Total synthesis of (+/-)-neovibsanin B.

(+/-)-Neovibsanin B was synthesized based on a DMI-accelerated intramolecular Diels-Alder reaction followed by oxy-Michael addition-lactonization. The synthetic (+/-)-neovibsanin B induced similar morphological changes in NGF-mediated PC12 cells compared with natural (+)-neovibsanin B.

Synthesis of riccardin C and its seven analogues. Part 1: The role of their phenolic hydroxy groups as LXRα agonists

Riccardin C, a nuclear receptor LXRalpha selective agonist, is an 18-membered macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin C and its seven O-methylated derivatives was accomplished. The synthetic sequence highlights an intramolecular Suzuki-Miyaura coupling in the formation of the 18-membered biaryl linkage present in riccardin C. The structure-activity relationship of these compounds suggests that all of the phenolic hydroxy groups present in riccardin C are essential for the activation of LXRalpha.

Novel NGF-potentiating diterpenoids from a Brazilian medicinal plant, Ptychopetalum olacoides

From the MeOH extract of Ptychopetalum olacoides, which is used in Brazilian folk medicine for the treatment of chronic degenerative conditions of the nervous system, four novel clerodane-type diterpenoids named 6alpha,7alpha-dihydroxyannonene (1), 7alpha,20-dihydroxyannonene (2), 7alpha-hydroxysolidagolactone I (3), and ptycho-6alpha,7alpha-diol (4) were isolated by bioassay-directed fractionation using NGF-differentiated PC12 cells. The structures of 1-4 were established by extensive NMR spectroscopic analyses and chemical conversion. Compounds 1 and 2 significantly enhanced NGF-mediated neurite outgrowth in PC12 cells at concentrations ranging from 0.1 to 50.0 microM for 1 and 0.1 to 30.0 microM for 2, whereas 3 and 4 had no morphological effect on NGF-mediated PC12 cells in the same concentration range. The structure-activity relationship of these compounds is also discussed.

Clerodane Diterpenoids with NGF-Potentiating Activity from Ptychopetalum olacoides

Four new clerodane-type diterpenoids, ptychonolide (1), 20-O-methylptychonal acetal (2), and an equilibrium mixture of ptychonal hemiacetal (3) and ptychonal (4), were isolated from the MeOH extract of the bark of a Brazilian plant, Ptychopetalum olacoides. The structure of 1 was elucidated as a clerodane-type diterpenoid on the basis of spectroscopic data, whereas 2 was assigned to an acetal derivative of 1. Compounds 3 and 4 existed as an equilibrium mixture. A mixture of compounds 3 and 4 was found to exhibit neurite outgrowth-promoting activities on NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10.0 microM.

NGF-potentiating vibsane-type diterpenoids from Viburnum sieboldii.

Six new vibsane-type diterpenoids, named neovibsanin O (1), neovibsanin M (2), neovibsanin L (3), (8Z)-neovibsanin M (4), 15-O-methylvibsanin H (5), and 5-epi-15-O-methylvibsanin H (6), were isolated from the leaves of Viburnum sieboldii by bioassay-guided fractionation using NGF-differentiated PC12 cells. The structures of 1-6 were established by analyzing their spectroscopic data and comparing their NMR data with those of previously reported vibsane-type diterpenoids. Compounds 3 and 4, and the known vibsane-type diterpenoids neovibsanins A (7) and B (8) significantly enhanced the neurite outgrowth of NGF-mediated PC12 cells at concentrations ranging from 20 to 40 microM.

Structures of furanovibsanins A–G from Viburnum awabuki

The structures of nine new 7-membered vibsane-type diterpenes named furanovibsanin A (1), 3-O-methylfuranovibsanin A (2), furanovibsanin F (3), furanovibsanin B (4), 7-epi-furanovibsanin B (5), furanovibsanin C (6), furanovibsanin D (7), furanovibsanin E (8), and furanovibsanin G (9), isolated from the leaves of Viburnum awabuki, were elucidated by intensive analyses of 2D NMR data and comparison of NMR data of the previously known vibsanins C and E. Their structures feature in a furan or a cyclic enol acetal ring forming on the C-4 and C-5 positions in vibsanin C (12).

Spirovibsanin A, an unprecedented vibsane-type 18-norditerpene from Viburnum awabuki

Abstract Spirovibsanin A, isolated from Viburnum awabuki , has been demonstrated to be an unprecedented vibsane-type 18-norditerpene consisting of a unique bicyclo[3.3.1] nonanespiro-γ-lactone framework by a combination of 2D NMR data and conformational analysis using MacroModel.