24159-07-7

Usage

Uses

Used in Antimalarial Applications:
Febrifugine is used as an antimalarial agent for its ability to reduce parasitemia and decrease mortality in mice infected with the P. berghei strain NK65. This application highlights its potential in combating malaria, a disease that affects millions of people worldwide.
Used in Anticancer Applications:
Febrifugine is used as an NRF2 inhibitor in the treatment of chemoand radio-resistant forms of cancer. It works synergistically with halofuginone, enhancing the effectiveness of cancer treatments. Additionally, Febrifugine analogs function as anticancer agents, further expanding the compound's potential in cancer research and therapy.
Used in Poultry Industry:
Febrifugine is used as a preventive agent for chicken coccidiosis, a disease caused by protozoan parasites that affect the intestinal tract of chickens. Its incorporation into the poultry industry helps reduce the prevalence of this disease, improving the health and productivity of the birds.

InChI:InChI=1/C16H19N3O3/c20-11(8-14-15(21)6-3-7-17-14)9-19-10-18-13-5-2-1-4-12(13)16(19)22/h1-2,4-5,10,14-15,17,21H,3,6-9H2

Upstream product

• 109813-59-4 3-{3-[(2RS,3SR)-1-ethoxycarbonyl-3-methoxy-2-piperidinyl]-2-oxopropyl}-4(3H)-quinazolinone 
• 675-20-7 piperidin-2-one 
• 491-36-1 4-quinazolinol 
• 683219-88-7 3-amino-3-tetrahydro[2]furyl-propionic acid 
• 223676-06-0 (S)-2-(benzyloxy)-5-(tert-butyldimethylsiloxy)pentanal 
• 32434-44-9 (+)-isofebrifugine 
• 330798-23-7 (3S)-trans-O-acetyl-N-benzyloxycarbonyl-febrifugine 
• 304665-12-1 (2R,3S)-3-benzyloxy-2-[2-oxo-3-(4-oxoquinazolin-3(4H)-yl)propyl]piperidine-1-carboxylic acid benzyl ester 
• 879898-98-3 (2R,3S)-2-(2-Methyl-allyl)-piperidin-3-ol 
• 757202-73-6 (5S,6R)-5-tert-butyldimethylsilyloxy-6-(2-methylprop-2-en-1-yl)piperidin-2-one 
• 757202-70-3 methyl (4S,5R)-4-tert-butyldimethylsilyloxy-5-(2-methylprop-2-en-1-yl)-L-prolinate 
• 879898-99-4 (2R,3S)-3-Hydroxy-2-(2-methyl-allyl)-piperidine-1-carboxylic acid benzyl ester 
• 757202-48-5 4-(tert-butyl-dimethyl-silanyloxy)-5-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 879899-01-1 (2R,3S)-3-benzyloxy-2-(2-oxopropyl)piperidine-1-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

Chiral synthesis of (+)-febrifugine and (-)-isofebrifugine by means of samarium diiodide-promoted carbon-nitrogen bond cleavage reaction

(+)-Febrifugine, a potential anti-malarial piperidine alkaloid, was synthesized from (4S)-hydroxyproline methyl ester, stereoselectively, where a samarium diiodide-promoted carbon-nitrogen bond cleavage reaction was involved as a key reaction. A stereocon

Total synthesis of dl-febrifugine and dl-isofebrifugine

Racemic compounds (1 and 2) of the antimalarial agents febrifugine (d- l) and isofebrifugine (d-2) were synthesized using an unusual Claisen rearrangement of allyl enol ether (7) and the stereoselective reduction of 2- allyl-3-piperidone (8). This method is widely applicable to the synthesis of derivatives needed to study the structure-activity relationship of febrifugine.

Stereocontrolled synthesis of a potent antimalarial alkaloid, (+)-febrifugine

A novel and stereocontrolled synthetic path to a potential antimalarial piperidine alkaloid, (+)-febrifugine, was established by employing a reductive deamination of a proline derivative with samarium diiodide, as a key step. A novel and stereocontrolled

Stereoselective Intermolecular [4+2] Process of N,O-acetals with Terminal Alkynes for Construction of Functional cis-Pyrido and Pyrrolo[1,2-c][1,3]oxazin-1-ones

A diastereoselective approach to access cis-pyrido and pyrrolo[1,2-c][1,3]oxazin-1-ones has been developed through a one-pot BF3 .Et2O-catalyzed [4+2] process starting with N,O-acetals and terminal alkynes. In addition, the utility of this transformation is demonstrated by the scalable synthesis of (+)-Febrifugine in 7 steps from the N,O-acetal (15% overall yield). (Figure presented.).

An asymmetric synthesis of febrifugine, halofuginone and their hemiketal isomers

A new synthesis of both enantiomers of naturally occurring febrifugine (1) and its analogue halofuginone (3) are reported. This robust route relies on an enzymatic kinetic resolution (EKR)-cross metathesis (CM) sequence, performed on allylic alcohol 8. A diastereoselective Lewis acid-mediated cyclisation of resultant enone 6 affords piperidine 12. In relation to its enantiomeric excess, values of 87 and 88% e.e were obtained for both enantiomers of 12 and for (?)-12 this was increased to 98% e.e by conducting the resolution process twice. A bromination (featuring an in situ temporary alcohol protection), alkylation and amino-deprotection sequence finally afforded the target compounds (+)- and (?)-1, and (+)- and (?)-3. Studies demonstrate that, as their ammonium salts, the compounds are stereochemically stable. However, as their free-bases, particularly in chloroform, C-2 isomerisation occurs. This isomerisation has been taken advantage of synthetically to provide enantioenriched (+)-isofebrifugine (2) and both enantiomers of isohalofuginone (14).

Synthesis of (+)-febrifugine and a formal synthesis of (+)-halofuginone employing an organocatalytic direct vinylogous aldol reaction

The enantioselective organocatalytic direct vinylogous aldol reaction of γ-crotonolactone and a suitable aldehyde was utilized in the synthesis of a functionalized γ-butenolide. The γ-butenolide (aldol product) was stereoselectively converted into a 5-aminoalkyl butyrolactone, which isomerized to the key 2,3-disubstituted piperidinone, a common intermediate to (+)-febrifugine and (+)-halofuginone. Georg Thieme Verlag Stuttgart · New York.

METHOD FOR PREPARING HALOFUGINONE DERIVATIVE

A method for preparing a halofuginone derivative, in particular a method for preparing an inhibitor medicament expressed by specific I-type procollagen in the invention a condensate of formula (II) reacts for 12-35 hours in a catalytic hydrogenation solvent with the existence of Ni—B amorphous alloy catalyst, at the hydrogen pressure of 0.1-10 Mpa and at the temperature of 10-60° C., and then the catalyst is filtered, the filtrate is decompressed to recover the solvent, the pH value is regulated to obtain a crude product of formula (I), and the crude product of the formula (I) is refined to obtain a refined product of formula (I).

Dihydroxylation of vinyl sulfones: Stereoselective synthesis of (+)- and (-)-febrifugine and halofuginone

(Chemical Equation Presented) The asymmetric dihydroxylation of amino-functionalized vinyl sulfone 19 has been used for the 3-step preparation of 3-hydroxylpiperidine 24 in 86% enantiomeric excess. This enantiomerically enriched building block was used then to synthesize the naturally occurring antimalarial alkaloid febrifugine 1 and its antiangiogenic analogue, halofuginone 3.

Synthetic evaluation of an enantiopure tetrahydropyridine N-oxide. Synthesis of (+)-febrifugine

A study into the synthesis and synthetic utility of (S)-3-benzyloxy-3,4,5,6-tetrahydropyridine N-oxide is described. This nitrone is readily accessed from l-glutamic acid and the regio- and stereoselectivity of cycloaddition of this compound with a range

BF3·Et2O catalyzed diastereoselective nucleophilic reactions of 3-silyloxypiperidine N,O-acetal with silyl enol ether and application to the asymmetric synthesis of (+)-febrifugine

The asymmetric BF3·Et2O catalyzed nucleophilic reactions of 3-silyloxypiperidine N,O-acetal 10 with silyl enol ethers derived from ketones are described. (+)-Febrifugine 1, an antimalarial alkaloid, was successfully synthesized based