Our aim is to construct optically pure a-methyl lysine and proline analogues from a common synthon. Enzymatic desymmetrization (using PLE) of achiral diethyl 2-methyl-2-alkyl phthalimido malonate (1 ) gives us ethyl 2-methyl-2-alkyl phthalimido acid-ester (2 ) with high optical purity. Our synthetic strategy allows us to vary the �R� group of lysine from 1-6 methylene units and backbone of lysine as well from �a�-�ߔ, from the same common synthon. We obtained high optical purity in case of enzymatic hydrolysis of a- methyl lysine diesters with 2, 3 and 4 methylene groups in the side chain. The lysine half-esters containing 1 to 6 methylene units are predominantly with (R ) enantiomers. We have been able to obtain enantiomerically enriched t-Boc-Fmoc protected 1 and 4 carbon a-methyl-a-Lysine (5 ) and a-methyl-�-Lysine (7 ) from the common synthetic intermediate. We have also obtained (R )-a-methyl-�-proine (4 ) from the same common synthon 2  (n=2) through stereo controlled cyclization.

Enantiodivergent synthesis of unnatural α-methyl-lysine and proline analogs from a common synthon

245th National Meeting (2013)

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