Disclosed herein are compounds having Formula I, which are non-natural L-adenosine analogs. Also disclosed are their methods of making. Still further, disclosed are the uses of the disclosed compounds to treat cardiovascular disease, ischemia related injuries; and neurodegenerative diseases. The compounds disclosed herein have the formula: ##STR00001## wherein R.sup.1 and R.sup.2 are, independently, H, branched or straight-chain, substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl; R.sup.3 is branched or straight-chain, substituted or unsubstituted alkyl, hydroxy-alkyl, or --C(.dbd.O)NR.sup.6R.sup.7; and R.sup.4 and R.sup.5 are, independently, H, hydroxy, halogen, and NR.sup.8R.sup.9, wherein R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are, independently, H, branched or straight-chain, substituted or unsubstituted alkyl, alkenyl, alkynyl, or aryl.