61693-05-8Relevant articles and documents
Syncarpamide, a New Antiplasmodial (+)-Norepinephrine Derivative from Zanthoxylum syncarpum
Ross, Samir A.,Sultana, Gazi N. N.,Burandt, Charles L.,ElSohly, Mahmoud A.,Marais, Jannie P. J.,Ferreira, Daneel
, p. 88 - 90 (2004)
A new (+)-norepinephrine derivative, syncarpamide (1), along with a known coumarin, (+)-S-marmesin (2), and one known alkaloid, decarine (3), have been isolated from the stem of Zanthoxylum syncarpum. The structure of compound 1 was elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation, and CD analyses. Its absolute stereochemistry was elucidated by synthesis of its enantiomer and subsequent comparison of CD data. Characterizations of compounds 2 and 3 were based on spectral analysis and comparison with reported data. Compounds 1 and 3 showed antiplasmodial activity, with IC50 values of 2.04 and 1.44 μM against Plasmodium falciparum D6 clone and 3.06 and 0.88 μM against P. falciparum W2 clone, respectively. Compound 3 showed cytotoxicity at 56.42 μM, whereas compound 1 was not cytotoxic at 10.42 μM. Compound 1 was tested for hypotensive activity, but no activity was observed. Compound 2 showed no antiplasmodial or antimicrobial activities.
Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents
Aratikatla, Eswar K.,Valkute, Tushar R.,Puri, Sunil K.,Srivastava, Kumkum,Bhattacharya, Asish K.
supporting information, p. 1089 - 1105 (2017/08/03)
Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.
Synthesis of (S)-(+)-sotalol and (R)-(-)-isoproterenol via a catalytic enantioselective Henry reaction
Blay, Gonzalo,Hernandez-Olmos, Victor,Pedro, Jose R.
experimental part, p. 578 - 581 (2010/08/06)
A unified approach for the synthesis of (S)-(+)-sotalol and (R)-(-)-isoproterenol has been developed. The enantioselective Henry reaction of the appropriate aldehyde in the presence of a camphor-derived amino pyridine-Cu(II) complex was the key step of th
