Synthesis of SL0101 carbasugar analogues: carbasugars via Pd-catalyzed cyclitolization and post-cyclitolization transformations

Abstract

A general approach to the stereoselective synthesis of 5a-carbasugars has been developed. The route mimics our palladium-catalyzed glycosylation/postglycosylation approach to carbohydrates in that it also utilizes a highly regio- and stereospecific palladium-catalyzed allylation and postglycosylation reaction sequence for the installation of either D- or L-cyclitols. This cyclitolization/postcyclitolization sequence was used for the enantioselective synthesis of a cyclitol analogue of SL0101, its D-sugar enantiomer, as well as several acetylation pattern analogues.

Figure 1

RSK2 inhibitors SL0101 and its analogues

Scheme 1

De Novo Approach to normal sugar and carbasugar

Scheme 2

Synthesis of two α-Boc-enones from quinic acid

Scheme 3

Pd-Cyclitolization for α-Boc-enones with BnOH

Scheme 4

Post-cyclitolization transformation

Scheme 5

Pd-Cyclitolization for kaempferol with α-l-Boc-enone

Scheme 6

Synthesis of SL0101 5a-carbasugar α-l-glycoside 4

Scheme 7

Synthesis of SL0101 5a-carbasugar α-l-glycoside 5 & 6

Scheme 8

Synthesis of (ent)-6

Scheme 9

Synthesis of (ent)-5 & (ent)-4