The long underestimated carbonyl function of carbohydrates – an organocatalyzed shot into carbohydrate chemistry

Abstract

The aggressive and strong development of organocatalysis provides several protocols for the convenient utilization of the carbonyl function of unprotected carbohydrates in C-C-bond formation processes. These amine-catalyzed mechanisms enable multiple cascade-protocols for the synthesis of a wide range of carbohydrate-derived compound classes. Several, only slightly different protocols, have been developed for the application of 1,3-dicarbonyl compounds in the stereoselective chain-elongation of unprotected carbohydrates and the synthesis of highly functionalized C-glycosides of defined configuration. In addition, C-glycosides can also be accessed by amine-catalyzed reactions with methyl ketones. By a one-pot cascade reaction of isocyanides with unprotected aldoses and amino acids access to defined configured glycopeptide mimetics is achieved. Depending on the reaction conditions different origins to control the installation of configuration during the bond-formation process were observed.

Synergy Effects in the Chemical Synthesis and Extensions of Multicomponent Reactions (MCRs)—The Low Energy Way to Ultra-Short Syntheses of Tailor-Made Molecules

“…They all increase the application options for MCRs, such as MCR nanosystems and mechanochemical reactions [ 65 ]. MCRs have been also applied in polymer [ 74 ], nucleoside [ 75 ] and carbohydrate [ 76 ] chemistry. Main field of application remains the production of heterocyclic compounds and many natural products by means of MCR [ 38 , 42 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ], leading directly towards drug design and discovery [ 89 , 90 , 91 , 92 , 93 ].…”

“…The strong dependence of carbohydrate chemistry on protective groups is well known [ 171 ], but MCRs like Ugi reactions are insensitive to hydroxy groups and thus appropriate for application with carbohydrates as carbonyl component to save material synthesis steps. This has been achieved in a one-step U-3CR/lactonisation of D-ribose with α-amino acids (AA) and ethyl isocyanoacetate ( Scheme 19 ) [ 76 , 172 ], furnishing oxazepinones 24 in yields of around 50% up to 76%. The syn/anti values of 24 are 67/33 to 91/9.…”

Synergy Effects in the Chemical Synthesis and Extensions of Multicomponent Reactions (MCRs)—The Low Energy Way to Ultra-Short Syntheses of Tailor-Made Molecules

“…They all increase the application options for MCRs, such as MCR nanosystems and mechanochemical reactions [65]. MCRs have been also applied in polymer [74], nucleoside [75] and carbohydrate [76] chemistry. Main field of application remains the production of heterocyclic compounds and many natural products by means of MCR [38,[77][78][79][80][81][82][83][84][85][86][87][88][89], leading directly towards drug design and discovery [90][91][92][93][94].…”

Synthesis of 1,3-divalent glycoconjugates with diverse structures and their functionalization

“…8,9 The presence of a multiple number of chiral centres and the different relative orientation of the hydroxyl groups with respect to each other make carbohydrates a source of chiral backbones that can easily be diversely functionalized with the help of selective protection and deprotection methods. [10][11][12][13] Carbohydrates are frequently used for the synthesis of various structurally diverse biomolecules, such as multivalent compounds and glycoamino acid mimics. Compared to monofunctionalized glycoconjugates, multifunctionalized glycoconjugates with different functional groups in the same sugar moiety have a better binding affinity with various bacteria, virus or lectins.…”