A divergent strategy to synthesize gabosines featuring a switchable two-way aldol cyclization

Area of Science:

• Organic Chemistry
• Carbohydrate Chemistry
• Synthetic Chemistry

Background:

• Gabosines and their analogues are C7 carbasugars with significant structural diversity and biological potential.
• Their complex structures present challenges for efficient synthetic strategies.

Purpose of the Study:

• To explore a novel diversity-oriented approach for synthesizing gabosine-type carbasugars.
• To establish a tunable regioselective aldol cyclization for creating versatile intermediates.

Main Methods:

• A flexible precursor (2) was subjected to a regioselective aldol cyclization.
• Two distinct cyclization modes (A and B) were controlled by switching promoters.
• The resulting intermediates (3 and 10) were further elaborated into target carbasugars.

Main Results:

• Selective production of two key cyclohexa(e)nones (3 and 10) via controlled cyclization modes.
• Intermediate 3 was converted into eight known natural carbasugars.
• Intermediate 10 facilitated the first total synthesis of (-)-gabosine L and new syntheses of (-)-gabosine A, B, N, and O.

Conclusions:

• The developed approach offers a versatile platform for C7 carbasugar synthesis.
• The first synthesis of (-)-gabosine L confirms its chemical structure and absolute configuration.
• This method provides efficient access to a range of biologically relevant gabosine analogues.