New total synthesis and structure confirmation of putative (+)-hyacinthacine C 3 and (+)-5- epi -hyacinthacine C 3 .

A unique synthesis of polyhydroxylated pyrrolizidine alkaloids, namely (+)-hyacinthacine C ₃ and (+)-5- epi -hyacinthacine C ₃ is presented. The strategy relies on a 1,3-dipolar cycloaddition of an l-mannose derived nitrone, which owing to its great syn -stereoselectivity builds up the majority of the required stereocenters. The following key steps include Wittig olefination and iodine-mediated aminocyclisation, that provide two epimeric pyrrolizidines with the appropriate configuration. As a result, structure and steric arrangement of the first synthetically prepared (+)-hyacinthacine C ₃ are proved to be correct, clearly confirming the inconsistency with the stereochemistry assigned to the natural sample. With respect to the previously proven glycosidase inhibitory activities, the antiproliferative effect of (+)-hyacinthacine C ₃ and (+)-5- epi -hyacinthacine C ₃ was evaluated using several cell line models.
Competing Interests: There are no conflicts to declare.
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