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lished synthesis, however, provides convenient access to enantiomerically pure analogs [21].

As shown in Scheme 1.2.2, the synthesis starts from a chiral imine 4, which is prepared from ethylglyoxylate and (R)-phenylethylamine, by an aza-Diels-Alder reaction, leading to azabicyclooctene 5 in fair yield. This unsaturated precursor can be converted to pipecolic acid derivative 7 by ozonolysis and subsequent functional group transformations as depicted in Scheme 1.2.2.

Even more advantageous for use in peptide synthesis, azabicycloalkenes like 5 can be converted into aminodiols 8, thus avoiding the difficult coupling to substituted pipecolic acids (Scheme 1.2.3). Bicyclics 8 are easy to couple N-terminally with additional amino acids by standard coupling procedures to give dipeptides 9, which in turn can be cleaved oxidatively with sodium periodate. The resulting intermediate bisaldehydes like 10 cyclize intramolecularly, immediately, to give diazabicycloalkanes 11, rigid analogs of anti-pipecolyl peptides, in quantitative yield. These can be transformed into covalently fixed anti-pipecolyl mimics like 13 (Scheme 1.2.4). Alternatively, the aminal in 11 or 12 might be cleaved, after conversion of the aldehyde attached to C3 to a side-chain of choice, to give 3,6-disubstituted pipecolic acid derivatives.

As illustrated by the synthesis of 13, which can be viewed as a Gly-Hse (Hse = homoserine) mimic (Scheme 1.2.4), aminals of the general structure 11 serve as versatile educts for the preparation of pipecolyl-dipeptide analogs with fixed anti-peptide geometry. The stereochemistry of compound 13 was determined unambiguously by 2D NOESY NMR spectroscopy and is in accordance with a re-

CO2Et 5

CO2Et 5

R = -H, -CH(CH3)2, -(CH2)4NHBoc, -(CH2)2SMe, CH2CO2Me

N' N^NHCbz

CO2Et

R CbzN

CO2Et

0 0

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