Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Antitumor Activity from Thai Sponge Xestospongia Species, Pretreated with Potassium Cyanide

Abstract

Renieramycins M (1m) and N (1n) were isolated from the Thai sponge Xestospongia sp., pretreated with potassium cyanide in methanolic buffer solution, and their structures and relative stereochemistries were elucidated on the basis of spectroscopic data. This strategy is the first example of the gram-scale preparation of this series of compounds and presents a potential solution for increasing the gram-scale supply of novel natural products from marine sources.

Jorunnamycins A-C, New Stabilized Renieramycin-Type Bistetrahydroisoquinolines Isolated from the Thai Nudibranch Jorunna funebris

“…All spectral data (IR, 1 H-NMR, 13 C-NMR, and HR-EI-MS) were in complete agreement with those of the compound derived from semisynthetic methods from 2m. [12][13][14][15] This is the first report of discovering 1a from the natural source.…”

“…All spectral data (IR, 1 H-NMR, 13 C-NMR, and HR-EI-MS) were in complete agreement with those of the compound derived from semisynthetic methods from 2m. [12][13][14][15] This is the first report of discovering 1a from the natural source.Jorunnamycin Jorunnamycins A-C (1a-c), three stabilized renieramycin-type bistetrahydroisoquinolines, were isolated from the mantles, the visceral organs, and the egg ribbons of the Thai nudibranch Jorunna funebris that was pretreated with potassium cyanide (KCN), along with five known compounds, renieramycins M (2m), N (2n), O (2o), and Q (2q) and mimosamycin (3). The structures of 1a-c were elucidated from spectroscopic data and by chemical conversion of renieramycin M (2m) into 1c via 1a.…”

“…that was also pretreated with KCN. 12) As series of our search for new metabolites via the isolation and characterization of biologically active compounds from Thai marine animals, we found the Thai nudibranch J. funebris feeding on the blue sponge Xestospongia sp., growing around Sichang Island in the Gulf of Thailand. In this paper, we present the isolation, structure elucidation, and cytotoxicity of three stabilized bistetrahydroisoquinolines jorunnamycins A-C (1a-c) from the KCN-pretreated J. funebris.…”

Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer Natural Products from Common Intermediate

“…13 C-NMR spectra were recorded at 100 MHz [multiplicities were determined from distortionless enhancement by polarization transfer (DEPT) spectra]. NMR spectra were measured in CDCl 3 , pyridined 5 or DMSO-d 6 and the chemical shifts were recorded in δ H values relative to (CH 3 ) 4 Si as the internal standard. All proton and carbon signals were assigned by extensive NMR measurements using correlation spectroscopy (COSY), HMBC, and heteronuclear multiple quantum coherence (HMQC) techniques.…”

“…by pretreatment with potassium cyanide. 6,7) Structure-activity relationship (SAR) investigations of a variety of derivatives of renieramycin M [8][9][10] yielded several pieces of evidence pointing to the fact that virtually all biologically active members of this family of natural products, such as 1, possess a carbinolamine or cyano function at C-21, which permits the formation of potent electrophilic iminium ion species 2, a compound that has been implicated in the formation of covalent bonds with DNA and possibly other bio macromolecules (Fig. 2).…”