Conhydrine: An Account of Isolation, Biological Perspectives and Synthesis

Abstract

Conhydrine is a naturally occurring 2-substituted piperidine alkaloid from the plant Conium maculatum L that exists in four different forms and is known for its high toxicity. This article focuses on the synthesis of conhydrine as its medicinal applications are limited due to its high toxicity. The various asymmetric methods developed for the synthesis of conhydrine are classified based on the methodology: the chiral pool method, the chiral auixiliary method, and asymmetric catalysis. A brief overview of the complete synthetic coverage of conhydrine in different isomeric forms is given.

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 .…”

“…[22] 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. [15] The rhodium(II)-catalyzed reaction of 8 with (S)-but-3-en-2-ol (2g, 97% ee) afforded (R,E)-2-(2-butenyl) 2-amino ketone 9 in 67% yield.…”

Total Synthesis of Natural Products and Medicinal Molecules via Chelation-Controlled Diastereoselective Hydride Reduction of Amino Ketones

“…Conhydrine, a natural product isolated from the seeds and leaves of the poisonous plant Conium maculatum, is a potent glycosidase inhibitor as well as it exhibits both antitumor and antiviral properties. 8,36 In 2012, our group disclosed 8 the total syntheses of piperidine alkaloid (+)-α-conhydrine and its pyrrolidine analog 25 using a highly diastereoselective chelation-controlled hydride reduction as the key step including RCM reaction.…”

Diastereodivergent Synthesis of (+)‐α‐Conhydrine and (−)‐β‐Conhydrine from a η,γ‐Dibromo‐β‐ketosulfoxide

“…Since its isolation by Wertheim in 1856 [3] and structure determination in 1933, [5] (+)‐α‐conhydrine ( 2 ) and its three stereoisomers (Figure 2) have attracted a great deal of interest from the synthetic community [6] . Since different stereoisomers of a chiral molecule may exhibit totally different biological and pharmacological activities, [7] developing alternative strategies allowing access to the four stereoisomers of conhydrine remains an important research goal to enable structure‐activity relationship studies of conhydrine family members [8] .…”

“…[4] Since its isolation by Wertheim in 1856 [3] and structure determination in 1933, [5] (+)-α-conhydrine (2) and its three stereoisomers (Figure 2) have attracted a great deal of interest from the synthetic community. [6] Since different stereoisomers of a chiral molecule may exhibit totally different biological and pharmacological activities, [7] developing alternative strategies allowing access to the four stereoisomers of conhydrine remains an important research goal to enable structure-activity relationship studies of conhydrine family members. [8] In particular, diastereodivergent strategies, in which more than one stereoisomer of conhydrine could be obtained from a common precursor via a diastereoselective reaction by varying the reaction conditions, would bring an effective solution in terms of atom and synthetic steps economy.…”