The first total synthesis of the marine acetylenic alcohol, lembehyne B – a selective inducer of early apoptosis in leukemia cancer cells

Abstract

The communication reports a new stereoselective method for the synthesis of a natural acetylenic alcohol, lembehyne B. The key stage of the process uses new cross-cyclomagnesiation reaction of aliphatic and oxygenated 1,2-dienes with Grignard reagents in the presence of a catalytic amount of CpTiCl. A study of the cytotoxic properties of lembehyne B on tumor cell lines using flow cytometry demonstrated that this is a selective inducer of early apoptosis of the Jurkat, HL-60 and K562 cell cultures and hypodiploid (sub-G1) sub-population inducer in cell cycle studies for all cell lines used.

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy

“…Among the screened organisms, Porifera showed selectivity against leukemia cell lines (134). Regarding the purified compounds from sponges with activity against CML, there are gombamide A, compound 1-8, Lembehyne B, Heteronemin, Smenospongine, Aaptamine, chujamides A and B (135)(136)(137)(138)(139)(140)(141)(142).…”

“…Lembehyne B, an acetylenic alcohol obtained from the sponge Haliclona sp. living in the Indonesian waters (137), exhibited cytotoxic properties against K562 cells showing an IC50 of 3 µM (138). In addition, Lembehyne B induced apoptosis and phosphatidylserine externalization on the plasmatic membrane after treatment.…”

Synthesis of New Cu Complex Based on Natural 5Z,9Z-Eicosadienoic Acid: Effective Topoisomerase I Inhibitor and Cytotoxin against the Cisplatin-Resistant Cell Line

“…At the end of incubation, the cells were analyzed on NovoCyte 2000 flow cytometry system (ACEA). 15 4.3.4. Cell Cycle Analysis.…”

Alkenyl Magnesium Compounds: Generation and Synthetic Application

“…The key step in this synthesis is the cross‐cyclomagnesation reaction of aliphatic 1,2‐diene and oxygenated 1,2‐diene, which provided (13 Z ,17 Z )‐tetraconta‐13,17‐dienal 131 after hydrolysis. 131 could undergo further transformation giving the final stereochemically pure product lembehyne B 132 in 49 % yield (Scheme ) …”

“…131 could undergo furthert ransformation giving the final stereochemically pure product lembehyne B 132 in 49 %y ield (Scheme 30). [62] When the 1,1-disubstituted N-containing 1,2-dienes were utilized in the cyclomagnesation reaction in the presence of Cp 2 ZrCl 2, as eries of magnesacyclopentanes 133 containing a C(sp 2 )ÀMg bond were generated as am ixture of trans-a nd cisisomers. The stereoselectivity of this reaction was closely related to the substituents of allenes(Scheme31).…”