Asymmetric synthesis of rubiginones A(2) and C(2) and their 11-methoxy regioisomers.
Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.
Carreño
M Carmen
MC
Departamento de Química Orgánica (C-I), Universidad Autónoma. Cantoblanco, 28049 Madrid, Spain. carmen.carrenno@uam.es
Somoza
Alvaro
A
Ribagorda
María
M
Urbano
Antonio
A
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D000095602:Angucyclines and Angucyclinones
D000880:Anthraquinones; C469875:rubiginone C(2); D000095602:Angucyclines and Angucyclinones; C045695:fujianmycin B