Synthesis and bioactivity of (±)-tetrahydrohaliclonacyclamine A

Alkylidene Dihydropyridines As Synthetic Intermediates: Model Studies toward the Synthesis of the Bis(piperidine) Alkaloid Xestoproxamine C

“…To date, the racemic synthesis of only one member of the family, haliclonacyclamine C ( 2 ), has been successfully completed as reported by Sulikowski in 2010 . The synthetic route developed in this effort was also subsequently applied to the construction of fully saturated racemic tetrahydrohaliclonacyclamine A . Apart from these studies, only two additional reports describing approaches to functionalized bis­(piperidine) ring systems have appeared.…”

Recent progress in neuroactive marine natural products

“…Spongederived adrenoceptor blockers such as aaptamine (168) 229 and hymenin (169) 230 were identied several decades ago. Aaptamine weakly inhibited the action of noradrenaline on a-adrenoceptors in vascular smooth muscles, while demethylaaptamine (170), demethyloxyaaptamine (171), dihydroaaptamine (172) and dihydrodemethylaaptamine (173) were inactive at the highest concentrations tested (10-100 mM). 229 Recently, aaptamine and 5,6-dibromo-N,N-dimethyltryptamine (174) were shown to exhibit antidepressant-like activity in the rodent forced swimming test model of depression.…”

“…211 Finally, the sponge cyclic imine derivative 115 , which interacts with mAChRs, also binds to the κ-opioid receptor. 173 These examples demonstrate that marine natural products afford an unexpectedly wide range of structural templates with affinity for opioid receptors. Future characterization of functional activity will be necessary to select promising lead compounds for further examination.…”

“…haliclonacyclamine A, 114), 115 and an epimer (116), have been synthesized in racemic form. 173 In an ion channel and GPCR assay panel, racemic 115 inhibited radioligand binding to muscarinic M1 receptor, opioid k receptors, and hERG potassium channels at 10 mM. Functional assays with the M1 muscarinic AChRs indicated that 115 was a full antagonist while 116 was a partial antagonist.…”

Intramolecular cyclizations of alkyl pyridines & alkylidene dihydropyridines as synthetic intermediates toward synthesis of bis(piperidine) alkaloids

“…Then compound 4.12 was subjected to ring closing alkyne metathesis (RCAM) followed by semihydrogenation of the cycloalkyne with Lindlar catalyst to afford haliclonacyclamine C (2.42). Furthermore, the synthetic route developed in this effort was also subsequently applied to the construction of fully saturated racemic tetrahydrohaliclonacyclamine A 164.…”