Decanoic Acid → 3-Hydroxydecanoic acid

HRID 1738769Notes

Reaction equation

HRID 1738769 reaction equation
[C:1]([OH:12])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].N1CCC[CH2:15][CH2:14]1.C(O[N:37]([CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C@@H:38]([C:44](O)=O)CCC(=O)O)(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=[O:20].[NH:54]1[C:58](=[O:59])[CH2:57][CH2:56][C@H:55]1[C:60](O)=O>>[CH2:52]=[CH:53][C@@H:48]1[C@@H:49]2[CH2:44][C@@H:38]([C@H:58]([OH:59])[C:57]3[C:56]4[C:55](=[CH:60][CH:1]=[CH:2][CH:3]=4)[N:54]=[CH:15][CH:14]=3)[N:37]([CH2:51][CH2:50]2)[CH2:47]1.[OH:20][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:2][C:1]([OH:12])=[O:11]

Participants

6

Reactant 4

HCID 2969Decanoic AcidHCID 7405L-Pyroglutamic AcidHCID 8082PiperidineHCID 131721400HCID 131721400, compound

Product 2

HCID 266123-Hydroxydecanoic acidHCID 101744Cinchonidine

Procedure

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.

Workup

  1. customthe selective removal of the base labile Fmoc group
  2. temperaturewhile maintaining the base insensitive Boc protection on the L-Ile
  3. customwas followed by piperidine-catalyzed Fmoc deprotection (20 minutes)

Sources & evidence

ORD record
ord-de05eb9f1860464c9ac0b9bd648253f7
Source dataset
uspto-grants-1999_10
Patent number
US05965524

Reaction notes

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