Alkaloids antimalarial

Our approach to the antimalarial alkaloid quinine focuses on strategic application of the manganese-mediated hybrid radical-ionic annulation. Retrosyntheti-cally, this is illustrated (Scheme 5) by disconnection of either of two C-C bonds... 

Few novel examples of the mono-heteronines have been reported recently. Azonane analogue 321 of antimalarial alkaloid ( )-deoxyfebrifugine is the product of an Eschenmoser sulfide contraction of intermediate thioimidate 320 (Equation 46, <2006SL383>). 

Tackie, A., Schiff, P., Sharaf, M. Antimalarial alkaloids from Cryptolepis sanguinolenta. WO9418203. PCT Int. Appl. (1994). 

Heptyl prodigiosin (43) [Fig. (13)] is another antimalarial alkaloid isolated from a tunicate. Precisely, this pigment was purified from a culture of a-proteobacteria isolated from a marine tunicate and showed an antimalarial activity similar to that of quinine against the chloroquine -sensitive strain P. falciparum 3D7 with an in vitro activity that was about 20 times the in vitro cytotoxic activity against mouse lymphocytes. When this molecule was tested in vivo, a single administration of 5 mg/Kg significantly extended the survival of P. berghei ANKA strain-infected mice but, unfortunately, the same dose caused sclerotic lesions at the site of injection [62],... 

Xiong and coworkers used an off-the-shelf antimalarial alkaloid, quinine derived enantiopure building block, HQA (6-methoxyl-(85, 9R)-cmchonan-9-ol-3-carboxylic acid, L,), to synthesize a homochiral MOPM, [CdCQA) ] (7, Scheme 1) with an open channel 3D structure, which crystallizes in a distorted octahedral geometry with two... 

Pham V, Jossang A, Grellier P, Sevenet T, Ngueyen V, Bodo B. Structure and total synthesis of (-)-myrioinidine and (—)-schoberine, antimalarial alkaloids from Myr-ioneuron nutants. J Org Chem 2008 73(19) 7565-73. 

In 2013, Chen and co-workers reported a streamlined approach for the s5mthesis of tetrahydroquinolines (THQs) via the sequential functionalization of remote C-H bonds [53]. Starting from readily available aryl iodide and aliphatic amine precursors, this strategy involved a three-step sequence including palladium-catalyzed y-C(sp )-H arylation, followed by a previously optimized metal-free e-C(sp )-H iodination reaction [54] and a more classical Cu-catalyzed intramolecular C-N coupling. To test the efficacy of this novel procedure, the authors applied it to the total synthesis of the antimalarial alkaloid (+)-angustureine (Scheme 7) [55]. N-Alkylpicolinamide 28 was easily accessible from commercially available (S)-(+)-3-... 

Cinchona plants yielded a crucial phytochemical resource to nineteenth century European people involved in trade and colonization of tropical lands - quinine [52], Before quinine, malaria was a major health issue in the new world, lowering quality of life by causing severe discomfort and even death. Quinine is an alkaloid present in the bark of several Cinchona species known as quina quina by native populations. It is most concentrated in Cinchona calisaya however, the most widely known quina quina plant became Cinchona officinalis officinalis means medical herb ). Besides quinine, Cinchona plants produce other antimalarial alkaloids, namely, quinidine, cinchonine, and cinchonidine. Cinchona alkaloids can be found in other Rubiaceae genera as well, as described for Remijia peruviana [53], Cinchona alkaloids have other bioactivities besides antimalarial. Quinine has been used to treat cramps [54]. Cinchonine is an inhibitor of MDR [55]. MDR is a detoxification mechanism present in certain cancer cell lines that renders them less sensitive to chemotherapeutic medications. Administration of cinchonine along with chemotherapeutic agents would result in better efficiency of treatment oti MDR cancer cells. 

Baker BR, Schaub RE, McEvoy FJ, Williams JH (1952) An antimalarial alkaloid from hydrangea. xii. synthesis of 3-[P-keto-y-(3-hydroxy-2-piperidyl) propyl]-4-quinazolone, the alkaloid. JOig Chem 17 132-140... 

---