1. A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid from geraniol
Mark C Noe, Joel M Hawkins, Sheri L Snow, Lilli Wolf-Gouveia J Org Chem. 2008 Apr 18;73(8):3295-8. doi: 10.1021/jo800080t. Epub 2008 Mar 14.
The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.
2. Convergent synthesis of (2R,3R,8R,9R)-N-Boc-ADDA
Sebastien Meiries, Rodolfo Marquez J Org Chem. 2008 Jul 4;73(13):5015-21. doi: 10.1021/jo800574g. Epub 2008 Jun 11.
The convergent synthesis of N-Boc-(2R,3R,8R,9R,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldecadenoic acid (enantio-N-Boc-ADDA) is reported. Our flexible approach takes advantage of highly efficient non-aldol aldol and cross-metathesis methodologies.
