Chemoenzymatic approaches toward dechloroansamitocin P-3.
[reaction: see text] The enantioselective total synthesis of proansamitocin, a key biosynthetic intermediate of the highly potent antitumor agent ansamitocin P-3, is described which bears a diene-ene RCM as the key macrocyclization step. Feeding of proansamitocin to an AHBA block mutant Actinosynnema pretiosum (HGF073) yielded ansamitocin P-3 as well as dechloroansamitocin P-3, the latter also being formed upon fermentation in the presence of 3-amino-5-methoxybenzoic acid.
Meyer
Axel
A
Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
Brünjes
Marco
M
Taft
Florian
F
Frenzel
Thomas
T
Sasse
Florenz
F
Kirschning
Andreas
A
D000192:Actinomycetales / Q000201:enzymology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure
D000970:Antineoplastic Agents; C520239:dechloroansamitocin P-3; C507695:seco-proansamitocin; D008453:Maytansine