Synthesis of allo- and epi-Inositol via the NHC-Catalyzed Carbocyclization of Carbohydrate-Derived Dialdehydes

Abstract

A synthesis of carbocyclic sugars from carbohydrate-derived dialdehydes using organocatalysis has been developed. Sorbitol, mannitol, and galactitol were converted via 1,6-tritylation, perbenzylation or permethylation, detritylation, and Swern oxidation into 2,3,4,5-tetra-O-alkyl-dialdoses that were cyclized via the benzoin reaction promoted by a triazolium carbene. Manno- and galacto-configured dialdehydes gave predominantly single inosose stereoisomers in up to 75% yield if the mixture was acetylated prior to isolation while the gluco-dialdehyde afforded a mixture of three stereoisomers in 61% overall yield. The inososes were stereospecifically reduced using sodium borohydride and then deprotected to give allo- and epi-inositol in good yield that confirmed the structural and stereochemical assignments.

ChemInform Abstract: The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo‐Inositol Chemistry)

“…allo-Inositol has been synthesized using carbohydrate dialdehyde intermediates in as imilar manner to epi-inositol (Scheme 18). [177] This route is attractive for reasons similar to those discussed for epi-inositol. Mannitol (143)was tritylated at the 1-and 6-positions to provide 144,t hen benzylation of the remaining hydroxy groups gave the fully protected intermediate 145.A cid hydrolysis of the trityl groups gave 146 and as ubsequent oxidation of the diol gave dialdehyde…”

“…Recently, allo-a nd epi-inositols have been synthesized from carbohydrate dialdehyde intermediates (Scheme 15). [177] In the presence of N-heterocyclic carbene catalysts,s uch as 124 and 125,t he dialdehyde derivatives gave cyclic acyloin products.T he cyclization of the dialdehyde intermediates synthesized from readily available starting materials is,there-fore,w orth highlighting,b ecause the limits of the chemical cyclization using these catalysts have not been widely explored. epi-Inositol was synthesized from sorbitol (126)b y ap rotection/deprotection strategy of tritylation to give 127, benzylation to form 128,a nd detritylation to generate 129.…”

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…[177] In the presence of N-heterocyclic carbene catalysts such as 124 and 125 the dialdehyde derivatives gave cyclic acyloin products. The cyclisation of the dialdehyde intermediates synthesised from readily available starting materials is therefore worth highlighting, because the limits of the chemical cyclisation using these catalysts have not been widely explored.…”

Die “anderen” Inositole und ihre Phosphate: Synthese, Biologie und Medizin (sowie jüngste Fortschritte in dermyo‐Inositolchemie)

“…In jüngerer Zeit wurden allo-u nd epi-Inositole über Kohlenhydrat-Dialdehyd-Zwischenprodukte synthetisiert (Schema 15). [177]…”