Trifluoroacetic acid → 3-Hydroxydecanoic acid

Participants

Reaction Steps

Synthesis of analogs (18), (20) and (21) proceeded by a shortened piperidine deblock of Fmoc-OBzl-D-Glu (Schiffler, R. J., et al., Amer. Med. Assoc. 251:2983 (1984)). The reduction of deblock from 20 to 5 minutes was necessary to prevent the cyclization (Hubert, A. J., et al., Helv. Chim. Acta 46:1429-1445 (1963)) of OBzl-D-Glu to pyroglutamic acid. The orthoganol Boc/Fmoc protection scheme allowed the selective removal of the base labile Fmoc group, while maintaining the base insensitive Boc protection on the L-Ile. The synthesis was continued by coupling of Fmoc-L-Leu (Keierszenbaum, F., Trop. Med. Parasit, Mansfield ed., Marcel Dekker, New York (1984)) in the usual manner (DCC/HOBT) which was followed by piperidine-catalyzed Fmoc deprotection (20 minutes) and final acylation with either (-)-D-3-hydroxydecanoic acid (-), structure (23) (for analogs (18) and (20)), or decanoic acid (for analog (21)). Coupling of D-3-hydroxydecanoic acid was as the Pfp ester (24), with the 3-hydroxyl group unprotected. The acid was obtained by (-)-cinchonidine resolution (Cartwright, N.J., Biochem. J. 67:663-669 (1957)) of synthetic (±)-3-hydroxydecanoic acid [(35)-(12)]. The (±)-3-hydroxydecanoic acid itself (mp 55°-56° C.; 57° C.) was synthesized by the aldol condensation of lithium tert butyl acetate (Rathke, M. W., et al., J. Amer. Chem. Soc. 95:3050-3051 (1973)) with n-octyl aldehyde, followed by TFA hydrolysis of the resulting (±)-tert butyl acetyl-3-hydroxydecanoic acid.

Provenance & Evidence