Enantioselective syntheses of (R)-pipecolic acid, (2R,3R)-3-hydroxypipecolic acid, β-(+)-conhydrine and (−)-swainsonine using an aziridine derived common chiral synthon

Abstract

Concise total syntheses of (R)-pipecolic acid, (2R,3R)-3-hydroxypipecolic acid and formal syntheses of β-(+)-conhydrine, (−)-lentiginosine, (−)-swainsonine and -1,2-di-epi-swainsonine have been accomplished starting from a common chiral synthon.

Synthesis of 2‐Substituted 2‐Amino Ketones by Rhodium‐Catalyzed Reaction of N‐Sulfonyl‐1,2,3‐triazoles with 2‐Alkenols

“…Conhydrine is a piperidine alkaloid isolated from the seeds and leaves of the poisonous plant Conium maculatum L., and its structure was elucidated in 1933 . Its potent biological activities have induced a number of investigations into its synthesis [23]. In our approach, the required triazole 8 was initially prepared from 1‐butyne ( 6 ) and tosyl azide ( 7 ) using copper(I) thiophene‐2‐carboxylate (CuTC) as the catalyst .…”

Alkylative Ring-Opening of Bicyclic Aziridinium Ion and Its Application for Alkaloid Synthesis

“…Among them piperidines as a six-membered aza-heterocycles are present in large number of biologically active natural products especially in the class of alkaloids. Many novel synthetic approaches have been developed for aza-heterocycles in an efficient manner to encounter regio-and stereoselective demand for the drug specification (Nicolaou et al, 1995; Masse et al, 2000; Kumar and Bodas, 2005; Trost et al, 2007; Srivastava and Panda, 2008; Chavan et al, 2015). However, no synthetic method is available to construct piperidine ring with concomitant introduction of the proper alkyl group at the alpha-position of the piperidine ring.…”

A Straightforward Synthesis of Six‐Membered‐Ring Heterocyclic α‐Aminophosphonic Acids from N‐Acyliminium Ions

“…It is well known that the presence of proline in peptide chain is crucial for protein structural and dynamic properties; thence, cyclic amino acids attract increasing attention in medicinal chemistry, and thus, structurally variable six‐membered‐ring heterocyclic amino acids have been introduced as building blocks for the preparation of bioactive compounds . Thus, intensive research efforts have been dedicated to their preparation, particularly pipecolic acid 1 , piperazine‐2‐carboxylic acid 2 , morpholine‐3‐carboxylic acid 3 , and thiomorpholine‐3‐carboxylic acid 4 . Additionally, these cyclic amino acids have also been used as precursors for the preparation of more complex scaffolds exhibiting pharmacological activities or acting as organocatalysts .…”