Synthesis of Echinamines A and B, the First Aminated Hydroxynaphthazarins Produced by the Sea Urchin Scaphechinus mirabilis and Its Analogues

• Published in: Journal of natural products (Washington, D.C.) Vol. 69; no. 8; pp. 1125 - 1129
• Main Authors: POKHILO, Nataly D., SHUVALOVA, Maria I., LEBEDKO, Maxim V., SOPELNYAK, Galina I., YAKUBOVSKAYA, Alla Ya, MISCHENKO, Natalia P., FEDOREYEV, Sergey A., ANUFRIEV, Victor Ph
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-08-2006; Glendale, AZ American Society of Pharmacognosy
• Subjects: Animals; Echinoidea; Molecular Structure; Naphthoquinones - chemical synthesis; Naphthoquinones - chemistry; Naphthoquinones - isolation & purification; Scaphechinus mirabilis; Sea Urchins - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0502185

The first total synthesis of two marine aminated hydroxynaphthazarins, echinamines A (3-amino-7-ethyl-2,5,6,8-tetrahydroxy-1,4-naphthoquinone) and B (2-amino-7-ethyl-3,5,6,8-tetrahydroxy-1,4-naphthoquinone), produced by the sea urchin Scaphechinus mirabilis is described. This was achieved from 1,2,4-triacetoxybenzene (13) through a sequence involving double Fries rearrangement of 13, reduction of 3,5-diacetyl-1,2,4-trihydroxybenzene (14), methylation of 3,5-diethyl-1,2,4-trihydroxybenzene (15), simultaneous double acylation of 3,5-diethyl-1,2,4-trimethoxybenzene (16) with a dichloromaleic anhydride-ethyl radical elimination process, methylation of 6,7-dichloro-3-ethyl-2-hydroxynaphthazarin (17), nucleophilic substitution of a chlorine atom by the methoxy group in 6,7-dichloro-3-ethyl-2-methoxynaphthazarin (18), introduction of an amino group via direct substitution of a chlorine atom in 7-chloro-3-ethyl-2,6-dimethoxy- (11) and 7-chloro-2-ethyl-3,6-dimethoxynaphthazarins (12) by an azido group, and functional group deprotection. The synthesis of amino analogues of spinazarin and spinochrome D is also described.