Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain 152

Abstract

Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1), [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3), were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152, together with four known microcystins, [ADMAdda5]microcystin-LR (4), [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS), collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas chromatography (GC) on a chiral capillary column. All three new toxins contained 9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda) instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit which was thought to be an invariable amino acid component of the microcystins. Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D-aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in 5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine unit in 4, would be a biosynthetic precursor of 4.