Chemistry of renieramycins. Part 6: Transformation of renieramycin M into jorumycin and renieramycin J including oxidative degradation products, mimosamycin, renierone, and renierol acetate

Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi-renieramycin G

“…With respect to the HCT-116 cell line, data obtained for 1 from this study (GI 50 1.9-2.4 nM) was in relatively good agreement with that recently reported by Saito and co-workers (IC 50 0.57 nM) on a sample prepared through semi-synthetic methods. 4 As well, our data acquired for 1 in the context of the A549 cell line (GI 50 19.2-24.3 nM) substantially agreed with that reported by Fontana and co-workers (IC 50 12.5 ng/mL (23.7 nM)). 2 Although (−)-jorumycin (1) displayed a nanomolar growth inhibition profile, the corresponding epimer, 3-epi-jorumycin (3), proved substantially less cytotoxic.…”

“…2 Saito and co-workers, employing (−)-jorumycin (1) prepared semisynthetically from renieramycin M, have reported potent antiproliferative activity for 1 against HCT-116 (IC 50 0.57 nM), QG56 (IC 50 0.76 nM), and DU145 (IC 50 0.49 nM) cell lines. 4 (−)-Renieramycin G (2) (Figure 1) was isolated from the marine sponge Xestospongia caycedoi by Davidson in 1992. 5 Despite having an amide carbonyl residue at C-21, 2 was reported to retain cytotoxicity against human cancer cells with MIC values of 0.5 µg/mL and 1.0 µg/mL against KB and LoVo cell lines, respectively.…”

“…1 Recently, we reported the asymmetric total syntheses of (−)-jorumycin (1) and (−)-renieramycin G (2). 6 However, en route to 1 and 2, a serendipitous discovery afforded a method to efficiently and selectively access two related natural product analogues, 3-epijorumycin (3) and 3-epi-renieramycin G (4). Preliminary biological evaluation of 3-epijorumycin (3), in addition to relevant synthetic intermediates, revealed low micromolar growth inhibition profiles for all compounds tested in the context of two human cancer cell lines (HCT-116 and A549).…”

Chemistry of renieramycins. Part 7: Renieramycins T and U, novel renieramycin–ecteinascidin hybrid marine natural products from Thai sponge Xestospongia sp.

“…2 In our ongoing search for new anticancer metabolites in Thai marine animals, we were able to identify several biologically active compounds from the tunicate Ecteinascidia thurstoni, 3 the blue sponge Xestospongia sp., 1,4,5 and the nudibranch Jorunna funebris. 6 However, all of our target natural products were isolable in only trace amounts and were relatively unstable, decomposing during extraction and isolation.…”

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

“…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).…”