Cytotoxic Alkylpiperidine Alkaloids from the Brazilian Marine Sponge Pachychalina alcaloidifera

Abstract

Four bis-piperidine alkaloids, madangamine F (1), haliclonacyclamine F (2). and arenosclerins D (3) and E (4), have been isolated from the marine sponge Pachychalina alcaloidifera and have been identified by analysis of spectroscopic data. The alkaloids displayed cytotoxic activity against different cancer cell lines. These results support the hypothesis of a common biogenetic origin for the Haplosclerida bis-piperidine and bis-pyridine alkaloids.

Total Synthesis of (±)‐Haliclonacyclamine C

“…A NOESY spectrum was used to establish relative stereochemistry of the bis-piperidine core ( Figure 13). 106 There were dipolar couplings between H2 and H4b, H2 and H9, H6b and H10b, and between H8b and H10b. This indicated that the relative stereochemistry of H3 and H2 was the same as haliclonacyclamine E (3.6).…”

“…106 There were dipolar couplings between H1, H3 and H5b, placing these hydrogens in an axial orientation. NOEs were also observed between H4b and H9, between H9 and H7, between H7 and H10a, between H6b and H10b, and between H10b …”

“…106 In all other haliclonacyclamines and arenosclerins the chain lengths are reversed, with the Nα to C7 connection being 10 carbons and the Nβ to C2 having 12 carbons.…”

“…36 Berlinck and co-workers have also shown that some arenosclerins have bioactivity as well. 106 With the synthesis of tetrahydrohaliclonacyclamine A (3. Table 4 below.…”

“…Despite the challenges encountered during structure elucidation of tetracyclic 3-alkylpiperidines, Crews, Garson, Berlinck, Kashman, and co-workers have isolated and determined structure for over sixteen tetracyclic alkaloids. [33][34][35][36][37]105,106 This chapter will examine structural differences and the assignment of relatively stereochemistry among this subgroup of 3-alkylpiperidine alkaloids.…”