Cyclobutastellettolides A and B, C₁₉ Norterpenoids from a Stelletta sp. Marine Sponge

Abstract

Two novel C 19 terpenoids (1, 2) with an unprecedented carbon skeleton (A) were isolated from a Stelletta sp. sponge collected from Vietnamese waters. Their structures and absolute configurations were established by extensive NMR, MS, and ECD analyses together with quantum chemical modeling and biogenetic considerations. The probable pathways of biogenesis of 1 and 2 from isomalabaricane triterpenoids are discussed. Compounds 1 and 2 significantly increase the production of reactive oxygen species in murine peritoneal macrophages.

Good Practices in Sponge Natural Product Studies: Revising Vouchers with Isomalabaricane Triterpenes

“…Of the 16 vouchers received, six were spicule preparations (all from the Naturalis Museum, Leiden, The Netherlands), nine were subsamples in EtOH or dried after EtOH extraction and one was from grinded powder (from the Muséum National d’Histoire Naturelle, Paris, France). Importantly, three NP studies out of 44 described the voucher in sufficient detail (external morphology and spicule measurements) so that we could confidently confirm [ 33 , 34 ] or revise [ 35 ] the identification before even seeing the voucher.…”

“…By collecting vouchers and voucher pictures, we noticed some shape variations in R. globostellata . This species is usually a massive subglobular species which can be cup-shaped in large specimens ( Figure 3 B), but a morphotype with a convoluted surface (brain-like) seemed also quite common ( Figure 3 A) in the South and East China Sea: ZMAPOR 16401 from Hirashima et al [ 55 ], ZMAPOR 12451 from Rao et al [ 19 ], PIBOC O38-301 from Kolesnikova et al [ 35 , 65 ], HM06-2016.1 from Kiem et al [ 62 ] and NCCT-B139 from Trang et al [ 66 ]. Morphology and measurements of the spicules from both morphotypes did not reveal any consistent differences.…”

“…It will significantly help other taxonomists to trust or not the identification. These descriptions can be in the Materials section (e.g., [ 33 , 101 ]) or in the Supplementary Information (e.g., [ 35 ]). This description should be mandatory if the specimen is identified to the genus level only.…”

Total Synthesis of (+)-Cyclobutastellettolide B

“…Cyclobutastellettolide B (1), which was originally isolated from a Stelletta sp. sponge (3.0 mg/1.3 kg) by Stonik et al in 2019, 1 can significantly increase the reactive oxygen species level in murine peritoneal macrophages (73 ± 12%) and is a potential lead for the development of immunomodulatory agents. 2 Compound 1 has an unusual 6/6/4-fused tricyclic core with six stereocenters; among them, three are contiguous quaternary stereocenters.…”

“…2 Compound 1 has an unusual 6/6/4-fused tricyclic core with six stereocenters; among them, three are contiguous quaternary stereocenters. Here, we report a concise enantioselective total synthesis of 1 via a late-stage biomimetic Norrish−Yang cyclization 1 to forge the highly compact cyclobutanone motif with three stereocenters. 3 The Norrish−Yang photocyclization has emerged as a powerful reaction for the synthesis of complex natural products.…”