ASYMMETRIC SYNTHESES OF 2,3-METHANOAMINO ACIDS
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1994 Georg Thieme Verlag, Rudigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. Some asymmetric syntheses of 2,3-methanoamino acids have used diastereoselective reactions to generate the requisite chiral centers, whilst others begin with natural chirons. Syntheses based on diastereoselective reactions have been used to produce modest amounts of 2,3-methanoamino acids, usually alkyl-or aryl-substituted analogs. Syntheses from naturally occurring optically active materials are generally more suitable for the preparation of side chain functionalized 2,3-methanoamino acids. One of the most useful chirons for this purpose is the cyclopropyl lactone chiron 43. This key starting material can be conveniently produced on a large scale from D-mannitol. Consequently, gram quantities of several functionalized 2,3-methanoamino acids can be made from this -lactone, including cyclo-Met, cyclo-Arg, cyclo-Arg', cyclo-Glu, cyclo-Gln, and cyclo-Asp derivatives. These facile routes to optically active 2,3-methanoamino acids will greatly accelerate biophysical and biochemical studies of peptidomimetics containing these useful and interesting protein amino acids surrogates.