Problem 51 of Chapter 6 presented a strategy for the synthesis of the amino acid (2S,3S)-3- hydroxyleucine, requiring as the starting material a specifi c stereoisomer of 2-bromo-3-hydroxy-4 methylpentanoic acid. Addition of bromine and water to the methyl ester of 4-methyl-2-pentenoic acid (margin) gives the corresponding ester of 2-bromo-3-hydroxy-4-methylpentanoic acid.

(a) Which stereoisomer of the unsaturated ester, cis or trans, is needed for this addition to give the necessary stereoisomer of the product?

(b) Can this strategy give the bromoalcohol as a single enantiomer or not? Explain, mechanistically.

Problem 51

(2S,3S)-3-Hydroxyleucine is an amino acid that is a key component in the structures of many “depsipeptide” antibiotics, such as sanjoinine (margin). (a) Find the part of the sanjoinine molecule that is derived structurally from (2S,3S)-3-hydroxyleucine. (b) Although many depsipeptide antibiotics occur in nature, the quantities available are too small to be useful pharmaceutically; thus these molecules must be synthesized. (2S,3S)-3-Hydroxyleucine, which is also not available in quantity from nature, must be synthesized as well. Possible starting materials are the four diastereomers of 2-bromo-3-hydroxy-4-methylpentanoic acid (margin). Draw structural formulas for each of these diastereomers and identify which of the four should be the best starting material for a preparation of (2S,3S)-3-hydroxyleucine.