Synthesis of (S)-(−)-Cucurbitine and Conformation of Its Homopeptides

Abstract

A chiral cyclic α,α-disubstituted α-amino acid, (S)-(−)-cucurbitine, which has a pyrrolidine ring with a chiral center at the α-position, was synthesized, and its homopeptides were prepared. (S)-(−)-Cucurbitine homopeptides with a Boc-protecting group formed helical structures with slight control of the helical screw sense to the left-handed form. The state of the pyrrolidine ring in (S)-(−)-cucurbitine was important for the control of the helical structures and helical screw sense of its homopeptides.

Application of Metathesis Protocols to the Stereocontrolled Synthesis of some Functionalized β‐Amino Esters and Azaheterocycles

“…Carbocyclic and azaheterocyclic β‐amino acids exert a growing interest in pharmaceutical and medicinal chemistry. Such molecular entities can be found in a large number of natural products, bioactive compounds, and drugs [1–19] . A wide variety of methods were developed during last two decades to obtain such derivatives [20–33] .…”

“…Cyclic β‐amino acids exert a wide range of biological properties, can be found in some natural products and drugs, and are promising building elements of various foldamers. As a result of this, such compounds and their synthesis was always a hot topic in pharmaceutical and medicinal chemistry [1–19,82–88] …”

Highly efficient and diastereoselective construction of substituted pyrrolidines bearing a quaternary carbon center via 1,3‐dipolar cycloaddition

“…Especially, lots of drugs and bioactivated compounds including pyrrolidine motifs exhibit remarkable pharmacological activities when the pyrrolidine ring bearing a quaternary carbon at C-3 position. For example, some representative examples of pyrrolidines containing quaternary stereocenter always exhibit a broad range of important biological activities (Figure 1), such as antibacterial agent [5], anthelmintic activity (Cucurbitine) [6,7], Amitifadine as the triple reuptake inhibitors [8], RORγt inverse agonists [9] and so on.…”

Highly Efficient and Diastereoselective Construction of Substituted Pyrrolidines Bearing A Quaternary Carbon Center via 1,3-Dipolar [3 + 2] Cycloaddition

“…Especially, lots of drugs and bioactivated compounds include pyrrolidine motifs exhibit remarkable pharmacological activities when the pyrrolidine ring bearing a quaternary carbon at C3 position. For example, some representative examples of pyrrolidines containing quaternary stereocenter always exhibit a broad range of important biological activities (Figure 1), such as antibacterial agent [5], anthelmintic activity (Cucurbitine) [6,7], anticholesteremic and immunomodulattor (SkandF 103811) [8], RORγt inverse agonists [9] and so on. Therefore, the development of efficient and novel synthetic methods for functionalized pyrrolidine scaffolds bearing a quaternary carbon center at C3 position has become an attractive objective.…”