1-tert-butyl 2-methyl (2R,3S)-3-hydroxypyrrolidine-1,2-dicarboxylate synthesis

Yield:> 99 % ee

Reaction Conditions:

with Bakers yeast

Steps:

6 Synthesis of the Pro3 Monomer Class; Example 6

The starting material for 37:pro3(2R3S) and 38:pro3(2R3R), the other two stereoisomers in the pro3 class can be synthesized using an established chemoenzymatic route. Non-fermenting bakers yeast reduction of the known ketoester 48 [37] has been used to synthesize the protected cis-3-Hydroxy-(D)-proline 39 with greater than 99% ee (Scheme 8). Gellman and co-workers have used a similar bakers yeast reduction to synthesize the starting material for the synthesis of their Fmoc-AP(Boc) beta-amino acid [38]. The building blocks 37:pro3(2R3S) and 38:pro3(2R3R) can be synthesized using the same approach as was used for 35:pro3(2S3R) and 36:pro3 (2S3S) but starting from cis-3-Hydroxy-(D)-proline.

References:

US2004/77879,2004,A1 Location in patent:Page 15