4396-01-4Relevant academic research and scientific papers
Biosynthesis of N-methylpelletierine: Vindication of a classical biogenetic concept
Hemscheidt, Thomas,Spenser, Ian D.
, p. 6360 - 6363 (1990)
The 13C NMR spectrum of a sample of N-methylpelletierine (2), generated biosynthetically from sodium [1,2,3,4-13C4]acetoacetate in Sedum sarmentosum Bunge, shows that the C3 side chain of the alkaloid is derived as an intact unit from the C4 precursor. The 13C NMR spectrum of a sample of the alkaloid, biosynthetically derived from sodium [1,2-13C2]acetate, shows that it is the -COCH3 unit and not the -CH2CO- unit of the side chain that is derived from an intact acetate precursor. These results constitute evidence in support of classical biogenetic concepts and disprove three other possible routes of biosynthesis.
Combining bio- and organocatalysis for the synthesis of piperidine alkaloids
Cairns, Ryan,O'Connell, Adam,O'Reilly, Elaine,Taday, Freya
supporting information, p. 1697 - 1700 (2022/02/21)
There is continued interest in developing cascade processes for the synthesis of key chiral building blocks and bioactive natural products (or analogues). Here, we report a hybrid bio-organocatalytic cascade for the synthesis of a small panel of 2-substituted piperidines, relying on a transaminase to generate a key reactive intermediate for the complexity building Mannich reaction.
Deciphering the Biosynthetic Mechanism of Pelletierine in Lycopodium Alkaloid Biosynthesis
Abe, Ikuro,Ding, Ning,Hnin, Saw Yu Yu,Jiang, Fang-Fang,Li, Jun,Liu, Xiao,Morita, Hiroyuki,Qi, Bo-Wen,Shi, She-Po,Tu, Peng-Fei,Wang, Juan,Wang, Xiao-Hui,Zhang, Ze-Kun
supporting information, (2020/11/13)
Pelletierine, a proposed building block of Lycopodium alkaloids (LAs), was demonstrated to be synthesized via the non-enzymatic Mannich-like condensation of Δ1-piperideine and 3-oxoglutaric acid produced by two new type III PKSs (HsPKS4 and PcPKS1) characterized from Huperzia serrata and Phlegmariurus cryptomerianus, respectively. The findings provide new insights for further understanding the biosynthesis of LAs such as huperzine A.
Deoxidized halofuginone compound and preparation method and application thereof
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, (2019/01/23)
The invention provides a deoxidized halofuginone compound. A structural formula of the deoxidized halofuginone compound is as shown in the specification, wherein R1 refers to a halogen radical or hydrogen; R2 refers to hydrogen, a halogen radical, C1-C3 alkyl, C1-C3 alkoxy or trifluoromethyl; R3 refers to hydrogen, a halogen radical, C1-C3 alkyl, C1-C3 alkoxy or trifluoromethyl; X1 or X2 refers tonitrogen or carbon; Y refers to hydrogen, hydroxyl or carbonyl. The synthetic deoxidized halofuginone compound with piperidine as a raw material has advantages of cheapness and easiness in acquisition of the raw material, simplicity and easiness in operation of a synthesis method, high yield and product stability. The deoxidized halofuginone compound has great inhibiting effects on Gram positive(Gram) and Gram negative (Gram) and has a promising application prospect in treatment of human and poultry bacterial infection.
Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine
Zaidan, Raed K.,Evans, Paul
, p. 5354 - 5367 (2019/06/25)
Three methods for the asymmetric synthesis of both enantiomers of pelletierine 6 are reported. Bella's proline-based Mannich process gave (R)- and (S)-Cbz-protected 6 in good yields from Δ1-piperideine 14 and in reasonable enantiomeric excess (74–80 % ee). An intramolecular aza-Michael, cinchona-based, organocatalytic method is also reported. With commercially available 9-amino quinine (24a) and quinidine (24b) catalysts, Cbz-protected α,β-unsaturated ketone 23 also gave (R)- and (S)-Cbz-protected 6 in good yields and enantiomeric excess (90–99 % ee). This material was used to synthesize both optically active forms of deoxyhalofuginone (26), an analogue of febrifugine which is of interest as an anti-fibrotic agent. Finally, a resolution of racemic pelletierine using (R)- and (S)-mandelic acid 27 is reported. This scalable method gave both enantiomers of Cbz- and Boc-protected 6 in excellent enantiomeric excess (≥ 99 %). Both highly enantioenriched forms of 6 (obtained from the resolution study) were used to synthesize several alkaloids. Firstly, (–)-(S)-Cbz-protected pelletierine 17 was used to prepare naturally occurring sedridine (32) and its epimer allosedridine (8). Then the preparation of both enantiomers of the quinolizidine myrtine (33) by an olefination-intramolecular aza-Michael sequence is reported. Finally, the synthesis of the epimeric quinolizidine alkaloids, lasubine I (34) and lasubine II (35), from (+)- and (–)-Boc-protected pelletierine (29) respectively, is discussed.
NHC-stabilised Rh nanoparticles: Surface study and application in the catalytic hydrogenation of aromatic substrates
Martinez-Espinar, Francisco,Blondeau, Pascal,Nolis, Pau,Chaudret, Bruno,Claver, Carmen,Castillón, Sergio,Godard, Cyril
, p. 113 - 127 (2017/09/08)
New Rh-NPs stabilised by N-Heterocyclic Carbenes (NHC) were synthesized by decomposition of [Rh(η3-C3H5)3] under H2 atmosphere and fully characterized. Surface studies by FT-IR and NMR spectroscopy employing isotopically labelled ligands were also performed. The Rh0.2 NPs are active catalysts in the reduction of various aromatic substrates. In the reduction of phenol, high selectivities to cyclohexanone or cyclohexanol were obtained depending on the reaction conditions. However, this catalytic system exhibited much lower activity in the hydrogenation of substituted phenols. Pyridine was easily hydrogenated under mild conditions and interestingly, the hydrogenation of 4-methyl and 4-trifluoromethylpyridine resulted slower than that of 2-methylpyridine. The hydrogenation of 1-(pyridin-2-yl)propan-2-one provided the β-enaminone 13a in high yield as a consequence of the partial reduction of the pyridine ring followed by isomerization. Quinoline could be either partially hydrogenated to 1,2,3,4-tetrahydroquinoline or fully reduced to decahydroquinoline by adjusting the reaction conditions.
Proline catalyzed, one-pot three component Mannich reaction and sequential cyclization toward the synthesis of 2-substituted piperidine and pyrrolidine alkaloids
Chacko, Shibin,Ramapanicker, Ramesh
supporting information, p. 2023 - 2026 (2015/03/18)
Abstract A very effective one-pot three component reaction of 4-bromobutanal or 5-bromopentanal, acetone, and p-anisidine catalyzed by proline is reported. A three component Mannich reaction followed by cyclization leading to the synthesis of 2-substituted pyrrolidine and piperidine derivatives through simultaneous formation of two C-N and one C-C bond is reported. The usefulness of the reaction is demonstrated by the synthesis of (±)coniine, (±)pelletrine, (±)sedridine, and (±)allosedridine.
Total synthesis of (±)-Vertine with Z-selective RCM as a key step
Chausset-Boissarie, Laetitia,Arvai, Roman,Cumming, Graham R.,Besnard, Celine,Kuendig, E. Peter
supporting information; experimental part, p. 6264 - 6266 (2010/10/19)
A concise total synthesis of the strained pentacyclic alkaloid (±)-Vertine has been achieved in eleven steps with the key steps being pelletierine condensation, Suzuki-Miyaura coupling, and ring-closing metathesis.
Metabolism of N-alkyldiamines and N-alkylnortropinones by transformed root cultures of Nicotiana and Brugmansia
Boswell, Henry D.,Draeger, Birgit,Eagles, John,McClintock, Carol,Parr, Adrian,Portsteffen, Andreas,Robins, David J.,Robins, Richard J.,Walton, Nicholas J.,Wong, Chi
, p. 855 - 869 (2007/10/03)
A range of analogues of N-methylputrescine and tropinone were fed to transformed root cultures of Nicotiana rustica and/or a Brugmansia candida x aurea hybrid. These cultures were made by the transformation of the relevant plant species with Agrobacterium rhizogenes. A number of the metabolites, notably those showing a relatively modest alteration in the N-alkyl substituent, were metabolized in vivo to form homologues of the normal alkaloids biosynthesized by these roots. These products were identified by GC/MS and comparison with some synthetic reference materials. Analogues with major alterations in the size of the N-alkyl substituent were not metabolized at all. In the N. rustica cultures, the analogues fed at 1 mM significantly affected the profile of normal alkaloids, with up to a 4-fold diminution in nicotine being found in the presence of N-n-propylputrescine. The ratio between alkaloids of the pyrrolidine series and the piperideine series was also affected. In contrast, the presence of the analogues in the B. candida x aurea hybrid culture at 1 mM did not inhibit or substantially interfere with the accumulation of the normal spectrum of alkaloids. The potential for using these cultures to make complex novel products from simple precursors is discussed.
Synthesis and Stereochemistry of Some New Diazatricyclic Compounds
Scheiber, Pal,Nemes, Peter
, p. 1033 - 1036 (2007/10/02)
The diazatricyclic ketone 3 was synthesized by a double Mannich condensation starting from 2-quinolizidone (2).Reductions of 3 by complex hydrides and hydrazine gave a mixture of isomeric amino alcohols rac-4/5 and the diamine 6, respectively.Compounds rac-4 and rac-5 could be separated by selective acylation with 4-chlorobenzoyl chloride due to the fundamental steric differences in the N --> O acyl transfer interactions within the isomeric molecules.The cis- and trans-4-phenyl-2-quinolizidones (rac-10, rac-11) also underwent a Mannich condensation affording the same product rac-12 in both cases. - Key Words: 7,11-Diazatricyclo2,7>tridecanes / Cytisine analogues
