Combining biocatalysis and organocatalysis for the synthesis of piperidine alkaloids.

There is continued interest in developing cascade processes for the synthesis of key chiral building blocks and bioactive natural products (or analogues). Here, we report a hybrid bio-organocatalytic cascade for...

The [4.3.0] piperidine alkaloids: architectures, biology, biosyntheses and the complete details of the asymmetric syntheses of streptazone A and abikoviromycin

Piperidine alkaloids continue to challenge the synthetic community by featuring densely functionalized scaffolds which often requires careful chemical orchestration. Streptazone A and abikoviromycin are small and highly functionalized piperidine alkaloids both accommodating Michael acceptors and a labile epoxide. These moieties are loaded into a [4.3.0] bicyclic core also present in other structurally related natural products including the well-known piperidine alkaloid streptazolin. Herein, we cover ring-closing strategies employed in prior streptazolin syntheses, provide a concise overview of structures, biological properties and biosyntheses of selected [4.3.0] piperidine alkaloids, and finally we disclose a complete coverage of our recent asymmetric syntheses of streptazone A and abikoviromycin.

A review of chemistry and pharmacology of Piperidine alkaloids of Pinus and related genera

Background: Pinus and other related conifers belonging to family pinaceae are most commonly used medicinal plants in Indian North-western Himalayas. Various parts of these plants including needles are source of several well known alkaloids. Of all the alkaloids, piperidine group is one of important component and hold considerable medicinal importance. Methods: The group of alkaloids was initially identified from genus Piper through which a large variety of piperidine molecules have been extracted. The planar structure of this heterocyclic nucleus enables acetamide groups to be added at various ring configurations. Results: In the area of drug research, the piperidine heterocycle has gained considerable interest. To produce a new therapeutic profile, the broad range of its therapeutic application paved the way for researchers to implant the nucleus from time to time in diversified pharmacophores. Discussion: However, biological functions of piperidine metabolites have been mostly examined on a limited scale and that most of the findings are thus preliminary. We have tried to present different clinical applications of piperidine alkaloids in this study that researchers have already attempted to demystify from time to time. Conclusion: Given the importance of the piperidine nucleus, the study will enable the researcher to produce scaffolds of the highest therapeutic efficacy. We have also illustrated different types of piperidine, its sources in different member of family pinaceae with special emphasis on Pinus.

Stereoselective synthesis of 2,6-disubstituted piperidine alkaloids

The synthetic methods to build the 2,6-disubstituted piperidine structural motif were described focusing on stereochemical control of two substituents at C2 and C6 with specific examples of natural products.

(+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense

In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation on the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense. In search for apoptosis, interestingly, trypanosomes treated with high concentration of compound 1 and 2 after 72 h significantly induced an early apoptosis-like programmed cell death (PCD) such as phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and caspases activation. No DNA laddering discriminated late apoptosis event. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense.