Statine and Related Compounds

Statine (4-amino-3-hydroxy-6-methylheptanoic acid, 6.95) is an important hydroxy amino acid with biological activities that have attracted considerable OH 

The most important method for preparing statine involves the conversion of leucine (tf.Pd) to leucinal derivatives 6.97). This aldehyde could then be condensed with a variety of nucleophilic reagents or with an ylid. In both cases, the carbon chain is extended and an acid moiety is incorporated. 

An early and typical synthesis shows the conversion of N-Boc-L-leucine methyl ester 6.98) to aldehyde 6.99. This aldehyde was condensed with the lithium enolate of ethyl acetate to give 6.100. Alcohol 6.100 was produced as a mixture of diastereomers and one of the important challenges of this strategy is to control the diastereoselectivity of the condensation. In this example, the 3S,4S diastereomer of 6.100 was separated and isolated (in 40% yield based on 6.99) and acid hydrolysis gave N-Boc statine 6.101)P  

Other methods for the preparation of 6.99 from leucine involved reduction of the acid moiety with borane and then oxidation to an aldehyde with chromium irioxide and pyridine. Another variation added zinc bromide to the enolate condensation reaction,75 which led to greater selectivity for the anti diastereomer. 

Wuts improved the selectivity of the condensation using 6.66 (which bears a chiral auxiliary see section 6.2.C) in a condensation reaction with 6.99This 

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