Millingtonine, an unusual glucosidal alkaloid from Millingtonia hortensis

Total Synthesis and Structural Revision of the Alkaloid Incargranine B

“…We therefore tentatively conclude that the natural product also exists as a diastereomeric mixture, although conclusive proof will require closer scrutiny of a sample isolated from the natural source 11. It is interesting to note that a biosynthetically related diglucosidic alkaloid, millingtonine,3b also exists as a mixture of diastereomers. The production of these pseudoenantiomeric diastereomers in nature is presumably due to either a late‐stage biosynthetic glucosidation of racemic (or scalemic) aglycones, or a lack of stereochemical influence exerted by the sugars in non‐enzyme‐mediated biosynthetic reactions.…”

Total Synthesis of Millingtonine

“…We considered that a phenylethanoid glycoside 2 , which contains an ornithine‐derived N ‐linked putrescine unit, might represent a reasonable biosynthetic precursor. Our biosynthetic proposal, which is shown in Scheme , involves a network of pathways that can account for the formation of several structurally distinct natural products isolated from Bignoniaceae plants: cornoside ( 3 ), rengyolone ( 4 ), incarviditone ( 5 ), incarvilleatone ( 6 ), incargranine B ( 7 ), and millingtonine ( 1 ) …”

Total Synthesis of Millingtonine

“…In 1996 Yamasaki and co‐workers isolated the alkaloid millingtonine ( 1 ) from Millingtonia hortensis , an ornamental Bignonia plant more commonly known as the indian cork tree . Millingtonine ( 1 ) was isolated as a mixture of two diastereomeric alkaloids, which contain a molecular framework not previously known to exist in the natural world.…”

“…Biosynthetically, millingtonine ( 1 ) is likely constructed from two shikimate‐derived C 6 C 2 units, linked together by an ornithine‐derived C 4 N unit (Scheme ). No biosynthetic pathway towards millingtonine ( 1 ) has been proposed and, as commented upon by the isolation team, “the mechanism of insertion of this (C 4 N) unit between the two C 6 C 2 units is unknown” …”

“…We considered that a phenylethanoid glycoside 2 , which contains an ornithine‐derived N ‐linked putrescine unit, might represent a reasonable biosynthetic precursor. Our biosynthetic proposal, which is shown in Scheme , involves a network of pathways that can account for the formation of several structurally distinct natural products isolated from Bignoniaceae plants: cornoside ( 3 ), rengyolone ( 4 ), incarviditone ( 5 ), incarvilleatone ( 6 ), incargranine B ( 7 ), and millingtonine ( 1 ) …”