An Efficient Regioselective Synthesis of Functionalized Spiropyrrolizidines through Azomethine Ylides Intermediate

Pyrrolizidines (4-azabicyclo[3.3.0]octane) are substantial core structures of many naturalproducts resembling alkaloids, and also occur in synthetic compounds with considerable bioactivities[1]. In particular, spiropyrrolizidines possess a privileged heterocyclic skeleton thatis recognized in a large family of synthetic compounds exhibiting versatile biological andmedical activities, such as antimycobacterial, antitumor, antifungal, and antiviral properties[2]. Another privileged structural core in the target compounds is rhodanine moiety, whichhas long been sought after by pharmacologists as an important structural motif in medicinalchemistry[3]. Herein we describe an efficient approach for the construction of functionalizedspiropyrrolizidine-linked rhodanines 4 through the 1,3-dipolar cycloaddition reaction of anazomethine ylide, generated in situ from L-proline (1) and dialkyl acetylenedicarboxylates,with rhodanine derivatives 3 for the synthesis of 4 in EtOH (Fig. 1). The structures of productswere characterized by their IR, mass spectral data, 1H NMR, 13C NMR, and X-ray crystallography.Various advantages of these transformations will be presented and discussed.