ASYMMETRIC SYNTHESES OF 2,3-METHANOAMINO ACIDS

Some asymmetric syntheses of 2,3-methanoamino acids have used diastere oselective reactions to generate the requisite chiral centers, whilst others begin with natural chirons. Syntheses based on diastereoselecti ve reactions have been used to produce modest amounts of 2,3-methanoam ino acids, usually alkyl- or aryl-substituted analogs. Syntheses from naturally occurring optically active materials are generally more suit able for the preparation of side chain functionalized 2,3-methanoamino acids. One of the most useful chirons for this purpose is the cyclopr opyl lactone chiron 43. This key starting material can be conveniently produced on a large scale from D-mannitol. Consequently, gram quantit ies of several functionalized 2,3-methanoamino acids can be made from this gamma-lactone, including cyclo-Met, cyclo-Arg, cyclo-Arg', cyclo- Glu, cyclo-Gln, and cyclo-Asp derivatives. These facile routes to opti cally active 2,3-methanoamino acids will greatly accelerate biophysica l and biochemical studies of peptidomimetics containing these useful a nd interesting protein amino acids surrogates.