Synthesis of the natural products 3-hydroxymollugin and 3-methoxymollugin.
3-Hydroxymollugin 2 and 3-methoxymollugin 3 are cytotoxic compounds isolated as minor compounds from Pentas longiflora and Rubia cordifolia. Syntheses of 3-hydroxymollugin 2 and 3-methoxymollugin 3 were developed starting from easily available 3-bromomollugin 6. Surprisingly, it was found that the reaction of 3-bromomollugin 6 with sodium methoxide in methanol resulted in the formation of 3-methoxymollugin 3 and the ring-contracted methyl isopropenylfuromollugin 7. A mechanism for this ring contraction is proposed on the basis of a pericyclic retro oxa-6pi ring-opening reaction. A second synthesis of 3-hydroxymollugin 2 was based on epoxidation of methyl 3-(3-methylbut-2-enyl)-1,4-naphthoquinone-2-carboxylate 17 and subsequent reduction of the quinone moiety, ring transformation, and DDQ oxidation. The latter oxidation process results in 3-hydroxymollugin 2 along with the rearranged furomollugin 4, which is a ring-contracted analogue of the natural product mollugin 1.
Sastry
Mudiganti Naga Venkata
MN
Department of Organic Chemistry, Faculty of Bioscience Engineering. Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Claessens
Sven
S
Habonimana
Pascal
P
De Kimpe
Norbert
N
D001688:Biological Products / Q000737:chemistry*; D003500:Cyclization; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C550065:3-hydroxymollugin; C550066:3-methoxymollugin; D001688:Biological Products; D003603:Cytotoxins; D004365:Drugs, Chinese Herbal; D011714:Pyrans; C046245:rubimaillin