Biosynthetically, it has been suggested that the tetrasubstituted pyridine lodged in the limonoid alkaloids arises from a mexicanolide-type limonoid containing a C9-hydroxyl group such as 2-1 (Scheme 2), 4b or a limonoid at a different oxidation state. According to the biogenetic hypothesis put forth by Wu and co-workers, upon formation of the C9-alkoxide, a retroaldol reaction could ensue and thereby cleave the C9⎯C10 linkage. 4b Intermediate 2-2 could be formed following a protonation of the resulting enolate, and β-elimination of the C3-alkoxy group. Guo and co-workers proposed that in the presence of an ammonia equivalent, a condensation onto the C9carbonyl could give rise to 2-3, followed by an aza-Michael reaction and ensuing aromatization to produce xylogranatopyridine B (1-1). They also postulated that the related bislactone limonoid natural products may arise via a similar condensation event either onto the carbonyl at C9 or C1. Subsequently, after an oxa-Michael reaction with an appropriate oxygen nucleophile and pyridine synthesis, tetracyclic intermediate 2-4 would arise. The bislactone family members (2-5) would be furnished by a benzylic oxidation and lactonization. The co-isolation of xylogranatopyridine B (1-1) and bislactone limonoid alkaloids, such as granatumine A (1-2), suggests the possibility of such a late-stage benzylic oxidation step in the biogenesis. However, this hypothetical biosynthetic pathway has not been experimentally corroborated, and remains largely speculative.