ChemInform Abstract: Studies Towards the Synthesis of Guanidine Alkaloids; Synthesis of a Tricyclic Guanidine from Succinimide (original) (raw)
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Syntheses of Cyclic Guanidine-Containing Natural Products
Tetrahedron, 2015
Naturally occurring guanidine derivatives frequently display medicinally useful properties. Among them, the higher order pyrrole-imidazole alkaloids, the dragmacidins, the crambescidins/batzelladines, and the saxitoxins/tetradotoxins have stimulated the development of many new synthetic methods over the past decades. We provide here an overview of the syntheses of these cyclic guanidine-containing natural products.
A novel facile solid-phase strategy for the synthesis of N, N', N?-substituted guanidines
Tetrahedron, 2002
AbstractÐA new facile solid-phase synthesis of N,N 0 ,N 00 -substituted guanidines from an immobilised amine component is described. The resin-bound amine was reacted with di-(2-pyridyl)thionocarbonate to generate the isothiocyanate which was treated with aryl/alkyl amines to yield the corresponding resin-bound thiourea. Desulfurisation of the thiourea was readily achieved by treatment with triphenylphosphine dichloride, and further reaction with aryl/alkyl amines followed by acidic cleavage with tri¯uoroacetic acid yielded N,N 0 ,N 00 -substituted guanidines of excellent purity and in good yield. q
Tetrahedron Letters, 2007
In this Letter, we describe the unexpected reaction pattern of N,N 0 N 00-tri-Boc-guanidine (TBG) with amines at room temperature and under reflux conditions affording N-substituted guanidines and amidinoureas, potentially important compounds with extensive applications in medicinal chemistry. This investigation shows that TBG is an excellent, readily available common starting material for the synthesis of various N-alkyl guanidines as well as N-alkyl-N 0-substituted amidinoureas by simply manipulating the reaction conditions.
Bioorganic & Medicinal Chemistry Letters, 2008
Transformation of aminoacridines into N-acridinyl-N 0 -alkylguanidines is described. The chosen procedure allows introduction of pendent substituents (exemplified by N,N-dimethylaminopropyl chain) into key acridinyl thioureas, thus opening the way to structural diversity. Spectroscopic study and pK a determination show that the presence of the strongly basic guanidine has a dramatic influence on the ionization of the acridine nucleus by lowering the pk a value down to 4.49.
Synthesis and applications of C2-symmetric guanidine bases
Tetrahedron Letters, 2003
The preparation of the tetracyclic C 2 -symmetric guanidinium salts 5 and 11-13 is reported together with their application to enantioselective transformations. Scheme 1. Reagents and conditions: (a) TBDMSCl/imid (99%); (b) DIBAL-H (95%); (c) TosCl/Py (85%); (d) NaI/acetone (89%); (e) i. CH 3 COCHPPh 3 /nBuLi, ii. aq. CH 2 O (79%); (f) i. guanidine/DMF, ii. HCl/MeOH, iii. NaBF 4 (aq.) (44%).
Molbank, 2022
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2019
Toward a method for direct conversion of alkenes to cyclic guanidines, we report that 1,3-dipolar cycloadditions of 2-amido-1,3-diamino allylic cations with electron rich alkenes provides a new method for direct cyclic guanidine annulation. Generated under oxidative conditions, the 2-amido-1,3-diaminoallyl cations, react as 1,3-dipoles providing rapid access to 2-amino imidazolines through net (3+2) cycloadditions. The utility is demonstrated through a concise synthesis of the oroidin alkaloid, phakellin. The described 1,3-dipole also participates in net (4+3) cycloadditions with dienes. Several observations suggest a stepwise, ionic, net cycloaddition leading to initial carbocation formation as evidenced by initial formation of constitutional isomers and intervening eliminations. Complex aziridines are formed with dienes suggestive of nitrene intermediates and results in net tetra-functionalization of dienes.
European Journal of Medicinal Chemistry, 2019
Leishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000e30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, 1 H and 13 C NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC 50-ama 5.6 mM; SI ¼ 131.8) and LQOF-G7 (IC 50-ama 7.1 mM; SI ¼ 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis.