Gabosine A

Carbasugars, the carbocyclic analogues of sugars, constitute an important class of natural products with more than 140 members known and have attracted much attention due to their diverse biological activities like anticancer, antibacterial, herbicidal, and various enzyme inhibitory activities. As many carbohydrates are involved in various cellular signaling pathways, there is great interest in synthesis and biological exploration of carbasugars. Herein, we have developed a methodology to install an α,β-unsaturated aldehyde functionality on different inositols and derivatives by vinylogous elimination of the O-protecting group under mildly acidic condition. We have illustrated the versatility and utility of our methodology by the total syntheses of seven carbasugars viz. (-)-MK7607, (-)-gabosine A, (-)-epoxydine B, (-)-epoxydine C, (+)-MK7607, 1-epi-(+)-MK7607 and 1-epi-(+)-gabosine E.

Gabosines and their natural analogues, belonging to C7 carbasugars, have attracted great attention in synthesis due to their rich structural variety and promising biological activities. A new diversity-oriented approach for the gabosine-type carbasugars based on a tunable regioselective aldol cyclization of flexible precursor 2 is explored. Two cyclization modes (A and B) of the precursor can be well controlled by switching promoters to selectively produce two resulting cyclohexa(e)nones 3 and 10, both of which are versatile intermediates for various C7 carbasugars. After the conversion of 3 to eight natural carbasugars, the utility of intermediate 10 is illustrated by the first synthesis of (-)-gabosine L, as well as the new synthesis of (-)-gabosine A, (-)-gabosine B, (-)-gabosine N and (-)-gabosine O. The chemical structure and the absolute configuration of (-)-gabosine L are confirmed by its total synthesis.

(+)-Gabosines A (12), D (4), and E (5), which share the same trihydroxycyclohexenone skeleton, were synthesized from enone 11 as the common intermediate. The key building block 11 was accessed by an intramolecular aldol cyclization of a diketone derived from D-glucose (8).