A Concise Total Synthesis of Dehydroantofine and Its Antimalarial Activity against Chloroquine‐Resistant Plasmodium falciparum. Issue 17 (26th February 2021)

• Record Type: Journal Article
• Authors: Yamasaki, Naoto; Iwasaki, Ikumi; Sakumi, Kazu; Hokari, Rei; Ishiyama, Aki; Iwatsuki, Masato; Nakahara, Masataka; Higashibayashi, Shuhei; Sugai, Takeshi; Imagawa, Hiroshi; Kubo, Miwa; Fukuyama, Yoshiyasu; Ōmura, Satoshi; Yamamoto, Hirofumi
• Is Part Of: Chemistry. Volume 27:Issue 17(2021)
• Page Start: 5555
• Page End: 5563
• Publication Date: 2021-02-26
• Subjects: antimalarial drugs -- dehydroantofine -- density functional calculations -- Diels–Alder reactions -- pi interactions; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202100032
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels–Alder reaction of easily accessible 3, 5‐dichloro‐2 H ‐1, 4‐oxazin‐2‐one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine‐resistant Plasmodium falciparum . Abstract : Stacks of selectivity : The azahetero‐Diels–Alder reaction of 3, 5‐dichloro‐6‐pheny‐2 H ‐1, 4‐oxazin‐2‐one with a ethynylbenzene derivative proceeds with high regioselectivity due to π–π stacking interactions between the aromatic rings of each substrate. The transition state of the reaction is demonstrated by DFT calculations, and this regioselective Diels–Alder reaction is applied to the total synthesis of an antimalarial candidate, dehydroantofine.