Abstract:
Hyrtioseragamines A (67) and B (68) are heteroatom-rich alkaloids isolated from extracts of Hyrtios sp. marine sponge that possess a novel furo[2,3-b]pyrazine-2(1H)-one core (red) and a guanidine moiety (blue). This thesis describes the construction of the furopyrazine core of the hyrtioseragamines and the total synthesis of hyrtioseragamine A. We proposed a modified biosynthesis of hyrtioseragamine A from the dehydrodiketopiperazine debromobarettin (95) that could undergo oxidative cleavage to give the enedione 97. PaalKnorr cyclisation of enedione 97 would generate the intermediate acetal 98 that upon the favourable elimination of water would form the furopyrazine, and hence hyrtioseragamine A (67). A model system was established to test the modified biomimetic hypothesis. Attempts at the oxidative cleavage of dehydroDKP 134 to give enedione 92 were unsuccessful. However, the enedione 92 was prepared from glyoxal 218 and DKP 149, and underwent successful biomimetic furopyrazine formation to give 93 in the presence of sulfuric acid. Application of the established Paal-Knorr reaction conditions on guanylated enedione 270 did not afford hyrtioseragamine A (67). However, subjecting N-protected enedione 285 to the PaalKnorr reaction conditions gave furopyrazine 288 that was subjected to guanylation and reduction to hyrtioseragamine A (67). The 1H and 13C NMR spectroscopic data for synthetic 67 were in full agreement with that described in the isolation report.