ABSTRACT
Leishmaniasis is one of the major parasitic diseases, caused by obligate intracellular protozoa Leishmania, having high mortality as well as morbidity rate. As there is no human licensed vaccine available against leishmaniasis, chemotherapy remains the major way of combating this disease. Many disadvantages are known to be associated with the current drug regime including severe side effects and toxicity, long duration and expensive treatment, and the emergence of resistance. An alternative approach is being utilized to search for active molecules using natural sources, rather than relying on synthetic drugs. Many plant-derived secondary metabolites like phenolic compounds, steroids, quinones, etc. are being extensively investigated for their anti-leishmanial potential. One such group of complex phenolic compounds are diarylheptanoids. These compounds have been shown to exhibit anti-inflammatory, anti-parasitic, anti-fungal, and other pharmacological activities. In the present study, a set of sixteen tetrahydropyran derivatives including three natural products were obtained in lyophilized form. These compounds with trans-2,6-disubstituted tetrahydropyrans, Diospongin A, Diospongin B (isolated from Dioscorea spongiosa) and Centrolobine (Centrolobium sclerophyllum) as parent compounds were synthesized by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six-membered cyclic hemiacetals in the presence of iodine as a catalyst. All the sixteen synthesized tetrahydropyran derivatives were used for toxicity analysis against L. donovani promastigotes, amastigotes and THP-1-derived human macrophages. IC50 values and selectivity index were calculated for all the compounds. Out of these sixteen, five compounds showed the best effect in vitro in terms of both leishmanicidal activity and non-toxicity to human macrophages.
ABSTRACT
The first asymmetric total synthesis of (1S,5R,7S)-cryptorigidifoliol G and (1S,5R,7R)-cryptorigidifoliol G of the proposed natural product was achieved. The key steps in the synthesis involved Keck-Maruoka allylation, our own developed protocol for the construction of the trans-2,6-disubstituted dihydropyran, iodolactonization, cross-metathesis, Prins cyclization, and cis-Wittig olefination reaction. A comparison of the NMR as well as analytical data and thorough analysis of the 2D NMR suggested that the absolute stereochemistry of the proposed natural product is (1S,5R,7S)-cryptorigidifoliol G.
ABSTRACT
An efficient CuBr2-catalyzed diastereoselective allylation of a cyclic hemiacetal with allyltrimethylsilane as a nucleophile has been developed. The protocol offers a cost effective, protecting group tolerant, and operationally simple approach to 2,6-trans-disubstituted tetrahydropyran with excellent diastereoselectivity. Furthermore, the application of this methodology has been demonstrated in the total synthesis of decytospolides A and B and their C6-epimers.
ABSTRACT
A unified and concise first asymmetric total synthesis of (-)-citreoisocoumarin (2), (-)-citreoisocoumarinol (3), 12-epi-citreoisocoumarinol (4), and (-)-mucorisocoumarins A (5) and B (6) have been accomplished from the common intermediate (-)-6-O-methyl-citreoisocoumarin (1). Central to the synthetic approach is a regioselective gold(I)-catalyzed 6-endo-dig cyclization strategy for the construction of the isocoumarin skeleton. The other key steps in this approach included Sonogashira coupling, Tsuji-Wacker oxidation, Evans-Saksena's 1,3-anti-reduction, and Narasaka-Prasad's 1,3-syn-reduction. The synthetic results unambiguously confirmed the absolute configuration of the natural products mucorisocoumarins A and B as (-)-(10R,12S)-5 and (+)-(10S,12S)-6, respectively.
ABSTRACT
An efficient synthesis protocol for the preparation of trans-2,6-disubstituted tetrahydropyrans by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six membered cyclic hemiacetals in the presence of iodine is developed. This reaction proceeds smoothly under mild conditions employing a catalytic amount of molecular iodine. The feature of this novel conversion includes milder reaction conditions, broader substrate scope, functional group tolerance and good diastereoselectivity. The efficiency and practicality of the current method were successfully displayed in the total synthesis of diospongin A and B in good yields.
