Planar chirality due to a polysulfur ring in natural pentathiepin cytotoxins. Implications of planar chirality for enantiospecific biosynthesis and toxicity.
A low-energy pathway for pentathiepin racemization has been found using density functional theory (DFT) calculations. 3-[1,2,3,4,5]pentathiepin-6-yl-propylamine served as a model compound for tunicate-derived pentathiepins. Pentathiepin racemization becomes a low-energy process in the presence of a thiolate ion nucleophile. It is unknown whether the biosynthetic process for pentathiepins is enantiospecific (Bentley, R. (2005) Chem. Soc. Rev. 34, 609) or whether toxicity differs between enantiomers. However, the ease of thiolate ion attack on the polysulfur ring suggests that nucleophiles may induce optical instability on the laboratory time scale. The DFT study predicts that enantiospecific behaviors such as toxicity differences between P- and M-pentathiepins would be difficult to determine experimentally. The computed results fit into a broader picture that nucleophiles assist in ring-opening and equilibration reactions of polysulfanes.
Brzostowska
Edyta M
EM
Department of Chemistry and Graduate Center, and The City University of New York (CUNY), Brooklyn College, Brooklyn, New York 11210, USA.
Paulynice
Martine
M
Bentley
Ronald
R
Greer
Alexander
A
D003603:Cytotoxins / Q000096:biosynthesis / Q000737:chemistry* / Q000633:toxicity; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011437:Propylamines / Q000737:chemistry* / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry* / Q000633:toxicity; D013846:Thiepins / Q000737:chemistry* / Q000633:toxicity
C523352:3-(1,2,3,4,5)pentathiepin-6-yl-propylamine; D003603:Cytotoxins; D011437:Propylamines; D013440:Sulfides; D013846:Thiepins