2326-89-8Relevant academic research and scientific papers
Oxidation of isodrimeninol with PCC yields drimane derivatives with activity against candida yeast by inhibition of lanosterol 14-alpha demethylase
Heydenreich, Matthias,Iturra, Andres,Jiménez, Verónica A.,Marin, Victor,Opazo, Andres,Ortiz, Leandro,Paz, Cristian,Schmidt, Bernd
, p. 1 - 13 (2020/07/31)
Candida species cause an opportunistic yeast infection called Candidiasis, which is responsible for more than 50,000 deaths every year around the world. Effective treatments against candidiasis caused by non-albicans Candida species such as C. glabrata, C. parapsilosis, C. aureus, and C. krusei are limited due to severe resistance to conventional antifungal drugs. Natural drimane sesquiterpenoids have shown promising antifungal properties against Candida yeast and have emerged as valuable candidates for developing new candidiasis therapies. In this work, we isolated isodrimeninol (C1) from barks of Drimys winteri and used it as starting material for the hemi-synthesis of four sesquiterpenoids by oxidation with pyridinium chlorochromate (PCC). The structure of the products (C2, C3, C4, and C5) was elucidated by 1D and 2D NMR spectroscopy resulting in C4 being a novel compound. Antifungal activity assays against C. albicans, C. glabrata, and C. krusei revealed that C4 exhibited an increased activity (IC50 of 75 μg/mL) compared to C1 (IC50 of 125 μg/mL) in all yeast strains. The antifungal activity of C1 and C4 was rationalized in terms of their capability to inhibit lanosterol 14-alpha demethylase using molecular docking, molecular dynamics simulations, and MM/GBSA binding free energy calculations. In silico analysis revealed that C1 and C4 bind to the outermost region of the catalytic site of 14-alpha demethylase and block the entrance of lanosterol (LAN) to the catalytic pocket. Binding free energy estimates suggested that C4 forms a more stable complex with the enzyme than C1, in agreement with the experimental evidence. Based on this new approach it is possible to design new drimane-type sesquiterpenoids for the control of Candida species as inhibitors of 14-alpha demethylase.
Preparation of 9α-fluorinated sesquiterpenic drimanes and evaluation of their antifeedant activities
Abad, Antonio,Agullo, Consuelo,Cunat, Ana C.,Gonzalez-Coloma, Azucena,Pardo, David
supporting information; experimental part, p. 2182 - 2198 (2010/07/06)
The preparation of 9α-fluoro analogues of both natural and unnatural drimane-type sesquiterpenes is described. Their synthesis began with the initial preparation of methyl 8-keto-12-nordriman-11-oate from β-ionone and entailed the electrophilic fluorination of C-9 for the stereoselective introduction of the fluorine atom. The drimane skeleton was completed from, the intermediate 9α-fluoro-8-keto-12-nordrimane system by means of different reactions at the C-8 ketone carbonyl group, essentially Wittig methylenation, cyanohydrin formation or palladium-catalysed carbonylation of the corresponding enol triflate. Further manipulation of the functionalization derived from these key reactions allowed the preparation, among others, of 9α-fluorodrimanes, which are structurally and functionally related to albicanic acid, drimenin and olepupuane. Also described are the reactivities of some of the fluorine-containing systems prepared and a comparative study of the antifeedant activities of a selection of 9α-fluorodrimanes and the corresponding hydrogen analogues against several, insect species with different feeding ecologies (Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi), which revealed a significant increase in the antifeedant activities of some of the fluorinated drimane analogues.
The structure of laricinolic acid and its biomimetic transformation into officinalic acid
Erb, Bernhard,Borschberg, Hans-Juerg,Arigoni, Duilio
, p. 2307 - 2309 (2007/10/03)
Laricinolic acid (8), a new sesquiterpene of the drimane type, has been isolated from the wood-rotting fungus Laricifomes officinalis. Its structure was elucidated by spectroscopic means and confirmed via a correlation with the known drimenine derivative 13. Oxidation of 8 to 1, followed by a mild thermal treatment, furnished (-)-officinalic acid (4) in 65% yield. This transformation establishes the hitherto unknown absolute configuration of the latter. An independent correlation was achieved by pyrolysis of 4 which furnished (-)-dihydrooxoisodrimenine (14) of known absolute configuration.
A convenient synthesis of (+)-albicanol based on enzymatic function: Total syntheses of (+)-albicanyl acetate, (-)-albicanyl 3,4- dihydroxycinnamate, (-)-drimenol, (-)-drimenin and (-)-ambrox
Akita, Hiroyuki,Nozawa, Masako,Mitsuda, Ayumi,Ohsawa, Hitomi
, p. 1375 - 1388 (2007/10/03)
By using lipase 'PL-266' from Alcaligenes sp. enantioselective acetylation of (±)-albicanol 4 with isopropenyl acetate gave the enantiomerically pure (+)-albicanyl acetate 3 and (+)-albicanol 4. Deprotection of (+)-3 afforded the natural (+)-albicanol 4 which was converted to the natural products (-)-albicanyl 3,4-dihydroxycinnamate 7, (- )-drimenol 8, (-)-drimenin 9 and (-)-ambrox 10. (C) 2000 Elsevier Science Ltd.
Synthesis and Resolution of Albicanic Acid. Simple Access to Optically Active Drimane Sesquiterpenes
Ragoussis, Valentine,Liapis, Maria,Ragoussis, Nikitas
, p. 987 - 992 (2007/10/02)
The synthesis of albicanic acid (+/-)-(2) and the resolution to its enantiomers (+)-(2) and (-)-(2) are described.Determination of their optical purity was by (1)H n.m.r. spectroscopy of the corresponding methyl esters (+)-(1) and (-)-(1) with Eu(dcm)3.The absolute configuration of the acids (+)-(2) and (-)-(2) has been determined by transformation to their alcohols (-)-(5) and (+)-(5) and interrelation with the natural albicanol.An efficient formal total synthesis of both enantiomeric forms of three drimanic sesquiterpenes, drimenin (7), isodrimenin (8), and drim-7-ene-11,12-diol (9), presenting special synthetic interest, is reported, starting from the corresponding enantiomers of albicanic acid (2).
The Diels-Alder Route to Drimane related Sesquiterpenes; Synthesis of Cinnamolide, Polygodial, Isodrimeninol, Drimenin and Warburganal
Hollinshead, David M.,Howell, S. Christopher,Ley, Steven V.,Mahon, Michael,Ratcliffe, Norman M.,Worthington, Paul A.
, p. 1579 - 1589 (2007/10/02)
The stereospecific preparation of various 1-vinyl-2,6,6-trimethylcyclohex-1-enes (6) as potential diene precursors in the Diels-Alder reaction with dimethyl acetylenedicarboxylate have been investigated.The reaction of the parent diene (6a) with dimethyl acetylenedicarboxylate affords an adduct (18) in 94percent yield.This species was reductively isomerised using 10percent Pd/C/H2 and a mineral acid to give a trans-fused decalin diester (19).Reduction of (19) with lithium aluminium hydride afforded 1,4,4a,5,6,8,8a-octahydro-5,8,8a-trimethyl-1β,4aα,8aβ-naphthalene-1,2-dimethanol (24) a key starting material for the highly efficient syntheses of five drimane sesquiterpene natural products, cinnamolide (1), polygodial (2), isodrimeninol (3), drimenin (4), and warbuganal (5).Microbial oxidation reactions using C. elegans or A. niger of (2), (24), and (1) gave good yields of the corresponding 3β-hydroxy derivatives, (30), (31), and (32).Several other unusually substituted drimane derivatives are reported.
SYNTHESE TOTALE DU (+/-)POLIGODIAL, DE LA DRIMENINE ET DE COMPOSES APPARENTES A JONCTION DE CYCLE cis ET trans
Jalali-Naini, M.,Guillerm, D.,Lallemand, J-Y.
, p. 749 - 758 (2007/10/02)
Isomerization by base under kinetic or thermodynamic control of the Diels-Alder adduct of 1,3,3-trimethyl-2-vinyl-1-cyclohexene with dimethyl acetylene dicarboxylate leads to two isomers which, after catalytic hydrogenation, give in high yield starting materials for synthesis of trans and cis drimanes.A short total synthesis of (+/-)-polygodial and (+/-)-drimenine from one of these isomers is desribed.
