Step 1
Acetone |
|
Cat. I2 |
MeI |
|
Ag2O |
HOAc |
|
NaIO4 |
|
MeOH |
(CH3)2CHI2, CrCl4 |
|
THF/DMF |
1)L-(-)-alpha-amino- |
|
2)TFA/THF/H2O |
Commercially available alpha-D-glucoheptonic gamma-lactone was utilized as the starting material. The first reaction converted the reagent to a bis(acetonide) by treating it with catalytic I2. There was 10% of another bis(acetonide) that was removed via crystallization.
Methylation of the unprotected methyl group was achieved by utilizing Ag2O with methyl iodide.
This step deprotected the hydroxyl groups by the application of acetic acid. The expected vicinal diol was acquired. Every step afterwards required no form of chromatographic purification.
Oxidative cleavage of the vicinal diol was achieved by NaIO4 and produced the corresponding aldehyde.
The aldehyde was olefinated with a low-valent organochromium species by 1,1-diodoiosbutane (prepared from isobutyraldehyde) and Cr(II)Cl2. A 3:1 ratio of E and Z isomers resulted. The E isomer was isolated using preparative normal phase HPLC. The yield was low around 29% and other techniques like the Wittig reaction and the S. Julia olefination were tried with even lower yields of less than 10%.
First, commercially available L-(-)-alpha-amino-epsilon-caprolactam and lactone were stirred at reflux in i-PrOH to give a protected Bengamide E. The final step involved the hydrolysis of all the protection groups by TFA-promoted acetonide hydrolysis. The final product was purified by reverse phase HPLC to obtain a white solid. Identification was determined by optical rotation and NMR spectroscopy.