NMR study of diastereoisomerism of 2-(1-aminoethyl)bicyclo[2.2.1]heptane and its hydrochloride (deitiforin)

The assignment of the signals for the H and C atoms of four diastereomers. (without their separation) of 2-(1-aminoethyl)bicyclo[2.2.1]heptane (1) and its hydrochloride (2) (the antiviral drug deitiforin) was performed for th e first time by two-dimensional H-1 and C-13 NMR spectroscopy. The effects of the substituent at position 2 of norbornane on the chemical shifts of th e alpha-, beta-, and gamma -carbon atoms of the bicycle were examined using the increments for alkanes. The changes in the chemical shifts of the C(6) and C(7) atoms are substantially larger than those for the other C atoms, which made it possible to identify the exo and endo forms. Each of these fo rms exists as a mixture of two diastereomers. The effect of the positive ch arge of the N atom on the gamma -protons, which are closely spaced, but sep arated by a number of covalent bonds, was considered on going from amine 1 to hydrochloride 2. Based on significant changes in shielding of these H at oms, the configurations of the asymmetric center in the CHMe(NH2) substitue nt of the diastereomers were established.