A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

Abstract

Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D-and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and γ-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (-)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)-lentiginosine.

Double asymmetric induction in 1,3-dipolar cycloaddition of five-membered cyclic nitrones to 2-(5H)-furanones

“…The single asymmetric induction in the cycloaddition of chiral nitrone 2 to the non-chiral lactone 9 has been reported by Brandi et al 11 The authors have noticed formation of two cycloadducts 13 and 14 in a ratio of 84:16, respectively, as a result of an exo approach of the dipole to both sides of the dipolarophile. In light of Font et alÕs report, 10 one would expect exo rather than endo approach of reactants anti in relation to the 3-tert-butoxy group in the nitrone.…”

Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

“…This strategy is one of the best methods available to synthetic organic chemists for establishing pivotal stereocenters in optically active compounds [3][4][5][6][7]. The chiral pool is a versatile tool, comprising naturally occurring chiral molecules such as carbohydrates, amino acids, terpenes, alkaloids, and hydroxyacids [2,6].…”

“…Chiral pool materials are also inexpensive and commercially available, making them adequate for use in accessing natural products and bioactive compounds [2]. The usage of the chiral pool in asymmetric synthesis can be classified in three general categories, as shown in Figure 1: (a) chiral sources, used as building blocks containing built-in stereocenters for target molecules; (b) chiral devices, employed as useful tools for enantioselective catalysts and auxiliaries; and (c) chiral inducers, applied to the generation of new stereocenters in a substrate-controlled manner [1][2][3][4][5][6][7]. The chiral inducer strategy is a highly efficient method to exploit advantages of both the chiral source and device approach at the same time.…”

Stereocontrolled Cyclic Nitrone Cycloaddition Strategy for the Synthesis of Pyrrolizidine and Indolizidine Alkaloids

“…As a consequence, by increasing the electronegativity of the group on the C-3 position, the regioselectivity increases. [12] This strategy for the synthesis of nitrones does not allow the protection of hydroxy functionalities with silicon protecting groups. Indeed, scrambling of silicon from the secondary to the primary hydroxy groups in triols and tetrols 3 and 5 occurs.…”