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Catalytic Asymmetric synthesis of alkaloids sharing all-carbon quaternary stereocenter is one of
the challenging aspects of synthetic organic chemistry. Enantioselective syntheses of such targets having
contiguous all-carbon quaternary stereocenters invariably face great deal of difficulty. Towards this,
naturally occurring cyclotryptamine alkaloids and related bis-indole alkaloids (Figure) with impressive
diversity of biological activities drew our synthetic interest.[1] The majority of these alkaloids are believed
to arise in Nature from L-tryptophan following a series of enzyme catalyzed stereoselective reactions.
Although the biological activities of only a few alkaloids of this family has been studied in detail
because of their unavailability in significant quantities, a variety of alkaloids of this family show
antibacterial and cytotoxic activities.[2a] Few of the congeners are potent competitive substance P antagonist
with respect to human neurokinin-1[2b] and the cholecystokinin B receptor.2c Despite the reported
bioactivities of few congeners, a comprehensive biological screen of the majority of these classes of
alkaloids is yet to be undertaken. In addition, as nature produces a small quantity of these alkaloids, it is
therefore important to design asymmetric synthetic strategy that can utilize to access large quantity of these
targets.
Figure. Biologically active alkaloids sharing all-carbon quaternary stereocenters.
On the basis of the structural resemblance between alkaloids 1-5 shown in Figure, we thought of
developing unified strategy for the total syntheses of these targets. Towards this, we explored novel Pd(0)-
catalyzed enantioselective decarboxylative allylations that addresses installation of all-carbon quaternary
stereocenters. [3] Our synthetic endeavors towards this direction involving a catalytic enantioselective
strategy following a DYKAT[4] and its application in total syntheses of indole alkaloids will be discussed in
this talk.[5] |