New Statin Analogues: Super-Threonine Derivatives

Published on 16/04/2015

A set of new statin analogues, so called Super-Threonines, is available consisting of Fmoc protected L-enantiomers with all possible 4 stereoisomers of chiral centers in the side chain. They appear in nature as bridge building element in cyclodepsipeptides, like pipecolidepsin A, a compound which shows relevant cytotoxic activity in three human tumor cell lines (lung, colon, breast) and has unique structural features.

A set of new statin analogues, so called Super-Threonines, is available consisting of Fmoc protected L-enantiomers with all possible 4 stereoisomers of chiral centers in the side chain. They appear in nature as bridge building element in Pipecolidepsin A, a head-to-side-chain cyclodepsipeptide found in the marine sponge Homophymia lamellosa. This compound shows relevant cytotoxic activity in three human tumor cell lines (lung, colon, breast) and has unique structural features, with an abundance of non-proteinogenic residues, including several intriguing amino acids. (1)

Super-Threonines can be coupled in peptide synthesis with standard protocols (DCC/HOBt) without any protection of the OH group. Forming an ester with this OH group is more difficult than forming an amide bond. A route using symmetric anhydrides and DMAP with prolonged reaction times has been reported as a successful approach. (2)

New Statin Analogues: Super-Threonine Derivatives

References:

(1) The first total synthesis of the cyclodepsipeptide pipecolidepsin A; Marta Pelay-Gimeno, Yésica García-Ramos, Maria Jesús Martin, Jan Spengler, José Manuel Molina-Guijarro, Simon Munt, Andrés M. Francesch, Carmen Cuevas, Judit Tulla-Puche, Fernando Albericio; Nat. Commun. 2013; 4: 2352 doi: 10.1038/ncomms3352.
(2) Simple Machine-Assisted Protocol for Solid-Phase Synthesis of Depsipeptides; Jan Spengler, Beate Koksch, Fernando Albericio; Biopolymers (Peptide Science) 2007; 88(6); 823-828. DOI 10.1002/bip.20858.