Oxidation of acyclic alkenes and allyl and benzyl ethers with DIB/t-BuOOH/Mg(OAc)<inf>2</inf>

Oxidation of (11Z)-1′,2′-didehydrostemofoline with DIB/TBHP/Mg(OAc)2·4H2O resulted in oxidative cleavage of the C-11-C-12 double bond instead of the desired allylic oxidation of the 1-butenyl side chain. Stemofoline gave a similar result. The oxidation of more simple terminal alkenes was regioselective and gave vinyl ketones while allyl and benzyl ethers gave acrylate and benzoate esters, respectively. Allyl and benzyl ethers could be chemoselectively oxidized in the presence of a terminal alkene or benzyl group. Oxidation of an internal alkene was poorly regioselective, in contrast to the oxidation of 1-substituted cyclohexenes. © 2011 Elsevier Ltd. All rights reserved

Phytochemical, Synthetic and Biological Studies on Stemona and Stichoneuron Plants and Alkaloids: A Personal Perspective

This report is an overview of our research on phytochemical, synthetic and biological studies of the Stemona and Stichoneuron species of plants

Semisynthesis and acetylcholinesterase inhibitory activity of stemofoline alkaloids and analogues

Semisynthesis of the known Stemona alkaloids oxystemofoline (7) and methoxystemofoline (8) has been achieved starting from (11Z)-1′,2′-didehydrostemofoline (6), which confirmed their structures and absolute configurations. The synthesis of (1′R)-hydroxystemofoline (9) helped establish this compound as a natural product from Stemona aphylla. (1′S)- Hydroxystemofoline (10) and a number of related analogues were also prepared. In a TLC bioautographic assay, 9 was found to be the most active acetylcholinesterase inhibitor, but it was not as active as galanthamine

Synthesis of stemofoline analogues as acetylcholinesterase inhibitors

Thirty-two new stemofoline analogues were prepared from didehydrostemofoline for studies as AChE inhibitors. C-3 Side-chain modified amino, carbamate, triazole and oxazole stemofoline derivatives were prepared. In general the amine derivatives were found to be stronger inhibitors of AChE than their alcohol analogues that we previously reported. Compounds 5 and 26, with small C-3 side-chain substituents, were two of the most active inhibitors. Preliminary molecular docking studies suggested that these compounds may inhibit AChE by binding horizontally along the passage of the active-site gorge and block access to acetylcholine. © 2012 Elsevier Ltd. All rights reserved

Phytochemical Studies on Stemona aphylla: Isolation of a New Stemofoline Alkaloid and Six New Stemofurans

A new stemofoline alkaloid, (2′S)-hydroxy-(11S,12R)-dihydrostemofoline (3), new stemofurans M-R (8-13), and known compounds stemofoline (1), (2′S)-hydroxystemofoline (2), stemofuran E (4), stemofuran F (5), stemofuran J (6), and stilbostemin F (7) have been isolated from the root extracts of Stemona aphylla. The structures and relative configurations of these new compounds have been determined by spectroscopic data interpretation and from semisynthetic studies. These natural and semisynthetic alkaloids were tested for acetylcholinesterase inhibitory activities and were found to be 10-20 times less active than 1′,2′-didehydrostemofoline itself. Stemofurans 4, 6, 8, 11, and 13 were tested for their antibacterial and antifungal activities. Three of these showed antibacterial activities against MRSA with MIC values of 15.6 μg/mL

Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined

Influence of Salicylic Acid on Alkaloid Production by Root Cultures of Stemona curtisii Hook. F.

To enhance the production of oxyprotostemonine, stemocurtisine and stemocurtisinol (the important insecticidal alkaloids) by root cultures of Stemona curtisii Hook. F. (Thai vernacular, Non Tai Yak, Family Stemonaceae). The roots were cultured on semi-solid MS medium containing 1 mg/L NAA with different concentrations of salicylic acid for 16 weeks. The quantity of the individual alkaloids was determined by HPLC. The highest production of oxyprotostemonine (7.192 mg/g dw), stemocurtisine (0.039 mg/g dw) and stemocurtisinol (0.197 mg/g dw) occurred when the roots were stimulated by 500 mg/L salicylic acid

Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/ Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined. © 2013 The Pharmaceutical Society of Japan

Phytochemical studies on Stemona plants: Isolation of stemofoline alkaloids

Six new stemofoline alkaloids, (2′A)-hydroxystemofoline (5), (3′R)-stemofolenol (6), (3′S)-stemofolenol (7), 1′,2′- didehydrostemofoline-AT-oxide (8), the first C19 stemofoline alkaloid, methylstemofoline (9), and the first glycosidated Stemona alkaloid, stemofolinoside (10), and three known alkaloids, (2′S)-hydroxystemofoline (2), (HZ)-1′,2′-didehydrostemofoline (3), and (11E)-1′, 2′-didehydrostemofoline (4), have been isolated from a root extract of an unidentified Stemona species. The structure and relative configuration of these new alkaloids have been determined by spectral data interpretation and from semisynthetic studies. © 2005 American Chemical Society and American Society of Pharmacognosy