Total Synthesis of Indolizidine (+)‐223A

Abstract

We described the diastereoselective total synthesis of indolizidine (+)-223A in 10 % overall yield over 14 steps starting from 6-chlorohex-2-ynoate. Our strategy involved chain

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…Pyrrolidine 104 was subjected to Swern oxidation to give the 1,3-dicarbonyl compound 105 as a mixture of diastereomers. [93] At the same time, it is a precursor for the synthesis of the alkaloid indolizidine (+)-223 A (Scheme 23), first isolated from the skin of a Panamanian frog of Dendrobates pumilio species. [94] Catalytic oxidation of the pyrrolidine 106 multiple bond leads to methyl ketone 107, which was used to synthesize the cephalotaxine alkaloid (Scheme 24), [95] isolated for the first time from the plant Cephalotaxus harringtonii.…”

Stereodivergent Synthesis of Alkaloid (±)-223A and (±)-6-epi-223A via Rh-Catalyzed Hydroformylation Double Cyclization

“… 3 The correct introduction of the stereocenters represents the main challenge in the synthesis of the indolizidine system. Thus, various intellectual and elegant strategies were developed: Michael-type conjugate addition on a 2-piperideine system, 4 , 5 via an aza-Achmatowicz oxidation of a furfuryl system, 6 amine-mediated Michael addition to ynone followed by cyclization, 7 , 8 trialkylsilyltin-mediated cyclization of allene, 9 intramolecular Mannich reaction of a β-aminobutanone derivative, 10 intramolecular cyclization of a homoprolinate derivative, 11 , 12 intramolecular Schmidt reaction followed by ring opening metathesis, 13 and elaboration of a versatile tricyclic lactone precursor. 14 These approaches can be divided into two categories: formation of the piperidine ring prior to formation of the pyrrolidine ring and vice versa.…”