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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 33, Number 7
BKCSDE 33(7)
July 20, 2012 

From L-Ascorbic Acid to Protease Inhibitors: Practical Synthesis of Key Chiral Epoxide Intermediates for Aspartyl Proteases
Sun Ki Chang, Soon Mog So, Sang Min Lee, Min Kyu Kim, Kyoung Mee Seol, Sung Min Kim, Jae sung Kang, Dong Joon Choo*, Jae Yeol Lee*, B. Moon Kim*
L-Ascorbic acid, Protease inhibitors, Aziridine opening, HIV protease, Epoxide
Efficient synthetic routes were developed to prepare a sizable amount (4-15 grams) of the chiral epoxides 4-6 as versatile intermediates for the synthesis of aspartyl protease inhibitors of therapeutic interest such as HIV protease and β-secretase. Oxidative cleavage of the C(2)-C(3) double bond of L-ascorbic acid followed by functional group manipulation led to the preparation of the epoxide 10, which was opened with an azide to yield a common aziridine intermediate 12. Through opening of the aziridine ring of 12 with either a carbon or a sulfur nucleophile, chiral epoxide precursors 4-6 could be prepared for various HIV protease inhibitors. Except for the final low melting epoxides 5 and 6, all intermediates were obtained as crystalline solids, thus the synthetic pathway can be easily applied to a large-scale synthesis of the chiral epoxides.
2213 - 2218
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