19456-89-4Relevant academic research and scientific papers
Two chromone-secoiridoid glycosides and three indole alkaloid glycosides from Neonauclea sessilifolia
Itoh, Atsuko,Tanahashi, Takao,Nagakura, Naotaka,Nishi, Toyoyuki
, p. 359 - 369 (2003)
From the dried roots of Neonauclea sessilifolia, two new chromone-secoiridoid glycosides, sessilifoside and 7″-O-β-D-glucopyranosylsessilifoside, and three novel indole alkaloid glycosides, neonaucleosides A, B, and C, were isolated along with the main known glycosides, 5-hydroxy-2-methylchromone-7-O-β-D-apiofuranosyl-(1→6)- β-D-glucopyranoside, sweroside, loganin, grandifloroside, and quinovic acid 3β-O-β-D-quinovopyranoside-28-O-β-D-glucopyranoside. The structures of these new glycosides were determined by spectroscopic and chemical means. Neonaucleoside A and its C-3 epimer were prepared from secologanin and tryptamine.
A facile chemoenzymatic approach: One-step syntheses of monoterpenoid indole alkaloids
Zou, Hong-Bin,Zhu, Hua-Jian,Zhang, Liang,Yang, Liu-Qing,Yu, Yong-Ping,Stoeckigt, Joachim
, p. 2400 - 2404 (2010)
Facile chemoenzymatic syntheses of cytotoxic monoterpenoid indole alkaloids with novel skeletons and multiple chiral centers are described. Synthesis of these alkaloids was achieved by a simple one-step reaction using strictosidine and 12-aza-strictosidine as the key intermediates. Strictosidines were prepared by coupling of secologanin with tryptamine and 7-aza-tryptamine, respectively, using the immobilized recombinant Rauvolfia strictosidine synthase. A detailed stereochemical analysis is presented herein. The results provide an opportunity for a chemoenzymatic approach that leads to an increased diversification of complex alkaloids with improved structures and activities.
Synthesis and biochemical evaluation of des-vinyl secologanin aglycones with alternate stereochemistry
Bernhardt, Peter,O'Connor, Sarah E.
, p. 7118 - 7120 (2009)
Based on the X-ray structure of the enzyme strictosidine synthase, the glucose moiety of the seco-iridoid glucoside, secologanin, appears to be the key for orienting the substrate. We hypothesized that removing the glucose moiety would allow alternate stereoisomers of secologanin to be turned over. A convenient synthesis to prepare stereoisomers of des-vinyl secologanin is presented. The choice of protective group was the key to access this series of compounds. The analogs were assayed with strictosidine synthase and, interestingly, both the natural 2,4-trans diastereomer and the unnatural 2,4-cis diastereomer are turned over. The trans/cis selectivity increases with increased acetal substituent size. The results add to our understanding of how strictosidine synthase discriminates among stereoisomers.
Strictosidine Synthase Triggered Enantioselective Synthesis of N-Substituted (S)-3,14,18,19-Tetrahydroangustines as Novel Topoisomerase i Inhibitors
Cai, Yunrui,Zhu, Huajian,Alperstein, Zaccary,Yu, Wenjun,Cherkasov, Artem,Zou, Hongbin
, p. 3086 - 3092 (2017)
Monoterpenoid indole alkaloids (MIAs) comprise an important class of molecules for drug discovery, and they have variant carbon skeletons with prominent bioactivities. For instance, in spite of limitations to their use, camptothecins are the only clinically approved topoisomerase I (Top1) inhibitors. The enzyme strictosidine synthase, which is key for MIA biosynthesis, was applied to the enantioselective preparation of three N-substituted (S)-3,14,18,19-tetrahydroangustine (THA) derivatives. These non-camptothecin MIAs were shown to have moderate in vitro HepG2 cytotoxicity and Top1 inhibition activities. The (S)-configured MIAs had stronger cytotoxicity and Top1 inhibition than their chemically synthesized (R)-enantiomers, which aligned with the results of molecular dynamics simulations. A series of N-substituted (S)-THAs were then chemoenzymatically synthesized to investigate structure-activity relationships. The most active analogue observed was the N-(2-Cl benzoyl)-substituted derivative (7i). Insight into the binding mode of 7i and a Top1-DNA covalent complex was investigated by molecular dynamics simulations, which will facilitate future efforts to optimize the Top1 inhibitory activities of non-camptothecin MIAs.
Deeper insights into the stereostructure of strictosamide tetraacetate and methylisoalangiside tetraacetate, the key reference molecules in monoterpenoid indole- and isoquinoline glucoalkaloids
Takayama,Ohmori,Subhadhirasakul,Kitajima,Aimi
, p. 1231 - 1233 (1997)
The highly shifted acetyl NMR signal of strictosamide tetraacetate, one of the most important reference molecules in the glucoindole alkaloid fields, is that on C2 of the glucose moiety. The signal that behaves similarly in methylisoalangiside tetraacetate was also confirmed to he that on C2.
Substrate specificity of strictosidine synthase
McCoy, Elizabeth,Galan, M. Carmen,O'Connor, Sarah E.
, p. 2475 - 2478 (2006)
Strictosidine synthase catalyzes a Pictet-Spengler reaction in the first step in the biosynthesis of terpene indole alkaloids to generate strictosidine. The substrate requirements for strictosidine synthase are systematically and quantitatively examined and the enzymatically generated compounds are processed by the second enzyme in this biosynthetic pathway.
First direct and detailed stereochemical analysis of strictosidine
Patthy-Lukats, Agnes,Karolyhazy, Laszlo,Szabo, Laszlo F.,Podanyi, Benjamin
, p. 69 - 75 (1997)
Using the easy lactamization of vincoside (4), epimer-free strictosidine (1) was prepared from secologanin (2) and tryptamine (3). 2D NMR methods were used to determine unambiguously the 1H- and 13C-NMR chemical shifts, the 1H-1H and 13C-1H coupling constants, and the 1H-1H NOE interactions in strictosidine (1). A minimal number of spectroscopic parameters (11 coupling constants, 3 NOEs) and some theoretical considerations have made it possible to select the single species of the 648 selected stereoisomers and to confirm directly the S configuration at the newly formed C-3 chiral center, the P helicity of the dihydropyran and tetrahydropyridine rings, and the conformations around C-14 and the glycosidic bridge.
Substrate specificity and diastereoselectivity of strictosidine glucosidase, a key enzyme in monoterpene indole alkaloid biosynthesis
Yerkes, Nancy,Wu, Jia Xin,McCoy, Elizabeth,Galan, M. Carmen,Chen, Shi,O'Connor, Sarah E.
, p. 3095 - 3098 (2008)
Strictosidine glucosidase (SGD) from Catharanthus roseus catalyzes the deglycosylation of strictosidine, an intermediate from which thousands of monoterpene indole alkaloids are derived. The steady-state kinetics of SGD with a variety of strictosidine analogs revealed the substrate preferences of this enzyme at two key positions of the strictosidine substrate. Additionally, SGD from C. roseus turns over both strictosidine and its stereoisomer vincoside, indicating that although this enzyme prefers the naturally occurring diastereomer, the enzyme is not completely diastereoselective. The implications of the substrate specificity of SGD in metabolic engineering efforts of C. roseus are highlighted.
Bacterial biotransformation of 3α(S)-strictosidine to the monoterpenoid indole alkaloid vallesiachotamine
Shen, Zhengwu,Eisenreich, Wolfgang,Kutchan, Toni M.
, p. 293 - 296 (1998)
3α(S)-Strictosidine produced by heterologously expressed strictosidme synthase from Rauwolfia serpentina was used in biotransformation experiments with a series of 22 bacterial strains.All strains tested were found to deglucosylate and rearrange the alkaloid to vallesiachotamine, thereby providing an example of how gene technology and microbial biotransformation can be combined for the biotechnological production of alkaloidal natural products. - Keywords: Rauwolfia serpentina, Spodoptera frugiperda, baculovirus, strictosidine synthase, vallesiachotamine.
Engineering strictosidine synthase: Rational design of a small, focused circular permutation library of the β-propeller fold enzyme
Fischereder, Eva,Pressnitz, Desiree,Kroutil, Wolfgang,Lutz, Stefan
, p. 5633 - 5637 (2014)
Strictosidine synthases catalyze the formation of strictosidine, a key intermediate in the biosynthesis of a large variety of monoterpenoid indole alkaloids. Efforts to utilize these biocatalysts for the preparation of strictosidine analogs have however been of limited success due to the high substrate specificity of these enzymes. We have explored the impact of a protein engineering approach called circular permutation on the activity of strictosidine synthase from the Indian medicinal plant Rauvolfia serpentina. To expedite the discovery process, our study departs from the usual process of creating a random protein library, followed by extensive screening. Instead, a small, focused library of circular permutated variants of the six bladed β-propeller protein was prepared, specifically probing two regions which cover the enzyme active site. The observed activity changes suggest important roles of both regions in protein folding, stability and catalysis.
