Aaptodines A–D,SpiroNaphthyridine–Furooxazoloquinoline Hybrid Alkaloids from the SpongeAaptos suberitoides

Abstract

LC−MS-oriented fractionation of the sponge Aaptos suberitoides resulted in the isolation of four heptacyclic alkaloids, aaptodines A− D (1−4), which contain 9,10-dihydrofuro[2,3-f ][1,3]oxazolo[5,4-h]quinolone and 7,8-dihydrocyclopenta[de][1,6]naphthyridine subunits with a spiro carbon atom. The structures were determined on the basis of NMR spectroscopic and single-crystal X-ray diffraction data analysis aided by electronic circular dichroism calculations and Mosher's method. A biosynthetic pathway for the formation of aaptodines A−D is postulated. Aaptodine D exhibits potent inhibition against osteoclast formation.

Trendbericht Organische Chemie 2022

“…Aaptodin A (145) ist ein spiro-Naph thy ri din-Fu ro oxa zo lo chino lin-Al ka lo id mit neuartiger Struktur, das aus dem Meeresschwamm Aaptos suberitoides stammt. 99) Thomas Lindel, TU Braunschweig th.lindel@tu-bs. de Alternativ eignet sich eine Halogenid-MT (HMT), um das demethylierte Cosubstrat S-Adenosylhomocystein (SAH) direkt zu alkylieren.…”

Biological Activity of Naturally Derived Naphthyridines

“…RANKL (Receptor Activator for Nuclear Factor κB Ligand) is a transmembrane protein that controls bone regeneration and remodeling. Wang et al [ 36 ] performed biological examination of four 1,6-naphthyridines analogues, aaptodine A–D 29 ( Figure 9 ), derived from Aaptos suberitoide . Aaptodine A–D 29 inhibited impressively RANKL-induced osteoclast formation and resorption, with the strongest effect for aaptodine D 29D .…”

One-Pot Multicomponent Coupling Reaction of Catechols, Benzyl Alcohols/Benzyl Methyl Ethers, and Ammonium Acetate toward Synthesis of Benzoxazoles

“… 1 − 3 For example, benzoxazole alkaloids, which are isolated from marine sponges or plants, showed potent pharmaceutical activities ( Figure 1 ). 4 − 8 …”

“… 4 , 9 Accordingly, the catechol precursor undergoes a domino oxidation/cyclization process to afford the final benzoxazole product. 4 Taking into consideration these biosynthetic pathways, the preparation of benzoxazole derivatives via the oxidation of catechols has received considerable attention. The coupling reaction of catechols with amines using a copper or iron catalyst system to produce the corresponding benzoxazoles was well developed ( Scheme 1 A).…”

“… 12 , 14 The chemical structures of aaptodines A–D showed that their difference related to a part of molecule which is originated to the amino acid backbone, confirming the importance of this transformation in the biosynthesis of benzoxazoles. 4 These approaches not only permit expedient synthesis of various benzoxazoles but also make possible the construction of structurally complex derivatives. Interestingly, a one-pot multicomponent coupling reaction of catechols, ammonium acetate, and aldehydes afforded benzoxazole derivatives in high yields ( Scheme 1 C).…”