Risch Pyridine Synthesis. Insight from the work of Risch and co-workers on the Kröhnke-type pyridine synthesis, 19 led us to surmise that the tetracyclic core of xylogranatopyridine B (1-1) could be assembled in a stepwise fashion and through the late-stage A-ring modification of 3-1, as depicted in Scheme 4A. It was proposed that 3-1 could be forged from the tricyclic pyridine fragment 4-1 via a four-step sequence involving aldol, acylation, intramolecular acetate aldol, and dehydration. Furthermore, the pyridine substructure in 4-1 could be assembled by a three-component coupling utilizing 1,3diketone 3-2, β-amino ketone hydrochloride 3-3, and ammonium acetate (Scheme 4A). This approach would allow for early introduction of the central pyridine structure, obviating the need to tame the reactivity of the nucleophilic furan or the electrophilic lactone.