Biomimetic Diels-Alder cyclizations for the construction of the brevianamide, paraherquamide, sclerotamide, asperparaline and VM55599 ring systems.
A potentially bio-mimetic Diels-Alder cyclization to construct the bicyclo[2.2.2] ring system common to the paraherquamides, marcfortines, sclerotamides, brevianamides, VM55599, and asperparaline is reported. Epi-deoxybrevianamide E (22) is converted into the corresponding lactim ether (23) and then oxidized with DDQ to provide an azadiene (24) which is tautomerized in the presence of base to azadiene 25 which, spontaneously cyclizes to give a 2:1 mixture of cycloadducts 26 and 27. These cycloadducts are each in turn, converted into D,L-C-19-epi-brevianamide A (20) and D,L-brevianamide B (6). The stereochemical implications of the [4 + 2] cycloaddition is discussed in the context of a working hypothesis on the biosynthesis of this family, particularly VM55599.
Department of Chemistry, Colorado State University, Fort Collins 80523, USA.
R M
RM
Williams
J F
JF
Sanz-Cervera
F
F
Sancenón
J A
JA
Marco
K M
KM
Halligan
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry; D010879:Piperazines; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D000871:Anthelmintics; D007212:Indolizines; D010879:Piperazines; D013141:Spiro Compounds; C116215:sclerotamide; C084043:VM 55599; C063985:paraherquamide; C116214:brevianamide B