Alkylation of nucleosides by dehydromonocrotaline, the putative toxic metabolite of the carcinogenic pyrrolizidine alkaloid monocrotaline

✍ Scribed by Haruki Niwa; Takeshi Ogawa; Osamu Okamoto; Kiyoyuki Yamada

• Book ID: 104225120
• Publisher: Elsevier Science
• Year: 1991
• Tongue: French
• Weight: 265 KB
• Volume: 32
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)92122-1

✦ Synopsis

Reaction of dehydmmonocrotaline

(3), the putative toxic metabolite of the carcinogenic pyrrolizidinc alkaloid monoerotahne (Z), with various nucleosides proceeded mostly at the C-9" position of 3 to give several nitrogen atom-alkylated nucleosides including N-7 alkylated 2'deoxyguanosine 14.

Pyrrohndine alla!oids having retronecine (1) or otonecine as the necine base portion exhibit marked hepatotoxicity and, in certain cases, carcinogemcity and antitumor activity.t

In particular, monocrotaline (2)

found in various species of CrotaZana plants is the best-known carcinogenic pyrrolizidine alkaloid and somenmes contaminates certain medicinal herbs and foodstuffs such as milk and honey.' The htghly reactive pyrrohc metabolite, dehydromonocrotaline (3) acting as a bifunctional electrophile is supposed to be responsible for the acute (liver leston) and the chronic (carcinogenicity) toxictty. 1 DNA cross-linking in vivo and in vitro has been observed with monocrotalme (Z), dehydromonocrotahne (3), dehydroretronecme (4). and the diacetate 5.2