[Systematic synthesis of antitumor annonaceous acetogenins].
Systematic synthesis of mono- and bis-THF ring cores, synthetic intermediates of antitumor annonaceous acetogenins, has been achieved by asymmetric alkynylation and subsequent stereodivergent THF ring formation as key steps. The asymmetric alkynylation of alpha-oxyaldehyde and alpha-tetrahydrofuranic aldehyde with (S)-3-butyne-1,2-diol derivatives gave good yield with very high diastereoselectivity. These adducts were converted into mono- and bis-THF cores via two kinds of one-pot THF ring formation, respectively. In addition, the total synthesis of murisolin, which shows cytotoxic activity against human tumor cell lines with potency from 10(5) to 10(6) times that of adriamycin, was also achieved.
Graduate School of Pharmaceutical Sciences, Osaka University, Suite, Osaka 565-0871, Japan. n-kojima@sagami.or.jp
Naoto
N
Kojima
D054378:Acetogenins; D029061:Annonaceae; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D055601:Organic Chemistry Phenomena; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D054378:Acetogenins; D000972:Antineoplastic Agents, Phytogenic; D005233:Fatty Alcohols; D007783:Lactones