Trifluoroacetic acid → 3-Hydroxydecanoic acid
Reaction equation
C(O)(C(F)(F)F)=O.C([C:12](C(=O)C)([CH:16]([OH:24])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[C:13]([OH:15])=[O:14])(C)(C)C>>[OH:24][CH:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:12][C:13]([OH:15])=[O:14]Participants
Procedure
Synthesis of analogs 18, 20, 21 proceeded by a shortened piperidine deblock of Fmoc-OBzl-D-Glu.41The reduction of deblock from 20 to 5 minutes was necessary to prevent the cyclization20 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-Leu42 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 (-) (23) (for peptides 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 resolution21 of synthetic (±)-3-hydroxydecanoic acid [(±) 12]. The (±)-3-hydroxydecanoic acid itself (mp 55°-56° C.; 57° C.) was synthesized by the aldol condensation of lithium tert butyl acetate22 with n-octyl aldehyde, followed by TFA hydrolysis of the resulting (±)-tert butyl acetyl-3-hydroxydecanoic acid.
Sources & evidence
- ORD record
- ord-8db9c15fa0044ca69d6d41e8b77a345f
- Source dataset
- uspto-grants-1992_12
- Patent number
- US05169862
Reaction notes
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