Methods and compositions are provided for efficiently preparing and
manufacturing pentostatin. Also provided are novel precursors of
pentostatin, pentostatin analogs and derivatives. In one aspect of the
invention, a method is provided for total chemical synthesis of
pentostatin via a route of heterocyclic ring expansion. For example, a
heterocyclic pharmaceutical intermediate for drugs such as pentostatin,
e.g., the diazepinone precursor, can be obtained efficiently through a
ring expansion of an O--C--N functionality in a hypoxanthine or
2'-deoxyinosine derivative. The methods and compositions can also be used
to synthesize and manufacture heterocyclic compounds other than
pentostatin, especially pharmaceutically important heterocyclic
compounds.