1-Bromo-2-methylbutane → 4-Methylnorleucine

HRID 355490Notes

Reaction equation

HRID 355490 reaction equation
[NH2:1][CH:2]([CH2:6][CH:7]([CH3:10])[CH2:8][CH3:9])[C:3]([OH:5])=[O:4].BrCC(C)CC.NC(C[C@@H](C)CC)C(O)=O>CO.O>[CH3:9][CH2:8][CH:7]([CH2:6][C@H:2]([NH2:1])[C:3]([OH:5])=[O:4])[CH3:10]

Participants

5

Reactant 3

HCID 252541-Bromo-2-methylbutaneHCID 520755HCID 520755, compoundHCID 12612090HCID 12612090, compound

Product 1

HCID 1927844-Methylnorleucine

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

Two, 2-amino-4-methylhexanoic acid (homoisoleucine, Hil) units were identified after analyzing the PS (phase sensitive) DQF COSY and TOCSY spectra of vitilevuamide. The stereochemistry of the amino acids was confirmed by chemical synthesis of all four diastereomers, and evaluation of the 1-fluoro-2,4-dinitrophenyl-5-L-alanineamide (FDAA; Sigma Chemical Co., St. Louis, Mo.) derived amino acids by HPLC on a cyano column. The mixtures of (2RS,4S) and all four isomers of Hil were synthesized starting from S-(+) and (±)-1-bromo-2-methyl butane (Sigma Chemical Co. or Aldrich Chemical Co., Milwaukee, Wis.) respectively using the method of H. Han & R. A. Pascal, 55 J. Org. Chem. 5173 (1990). The diastereomeric mixture of (2RS,4S)-2-amino-4-methyl hexanoic acid was treated with catalase and L-amino acid oxidase (Aldrich Chemical Co.) at pH 8 for 12-18 hours. Upon acidification and reverse phase chromatography (9:1, MeOH/H2O), the pure (2R,4S) isomer of Hil was isolated. Using these standards it was possible to verify the stereochemistry of the two Hil residues in vitilevuamide by FDAA derivatization and cyano HPLC chromatography (MeOH/1% Acetic acid, 25:75-90:10 at 1 mL/min) with UV detection at 340 nm.

Workup

  1. customThe mixtures of (2RS,4S) and all four isomers of Hil were synthesized

Sources & evidence

ORD record
ord-fc86f7c4e31441abaeee42f5810032cf
Source dataset
uspto-grants-1998_11
Patent number
US05830996

Reaction notes

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