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

• Published in: RSC advances 2021-09, Vol.11 (5), p.31621-3163
• Main Authors: Dikošová, Lívia, Oto ková, Barbora, Malatinský, Tomáš, Dohá ošová, Jana, Kopá ová, Mária, urinová, Anna, Smutná, Lucie, Trejtnar, František, Fischer, Róbert
• Format: Article
• ISSN: 2046-2069
• DOI: 10.1039/d1ra06225e

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. A second total synthesis of (+)-hyacinthacine C 3 is reported. As a result, structure of the first synthetically prepared alkaloid is proved to be correct, clearly confirming the inconsistency with the stereochemistry assigned to the natural sample.