Synthesis of C8-glycomimetics as potential glycosidases inhibitors

The synthesis of C8-glycomimetics is described from C₂-symmetrical polyhydroxylated cyclooctenes derived from carbocyclisation of enantiomerically pure 1,9-dienes by ring closing metathesis. Their obtention notably involved either hydroboration followed by oxidation to carbasugars or to cyclooctanones then reductive amination, or formation of a cis-cyclic sulfate followed by successive introduction of an azido group, reduction and subsequent reductive amination. The biological activity of the C8-carbasugars and related aminocyclitols, analogous to voglibose, has been evaluated towards several commercially available glycosidases.     

Stereoselective total synthesis of (−)-zeylenol,a key intermediate for the synthesis of (+)-pipoxide, (−)-uvarigranol G and (−)-tonkinenin A

Total synthesis of (?)-zeylenol, a key intermediate for the synthesis of (+)-pipoxide, (?)-uvarigranol G and (?)-tonkinenin A was achieved from commercially available starting material d-mannose. The key steps are mixed aldol condensation, Grignard reaction, ring closing metathesis and regioselective benzoylation.     

Synthesis of branched carbasugars via photooxygenation and manganese(III) acetate free radical cyclization

Transformation of cyclohexa-1,3- and 1,4-dienes to carbasugars is described. Photooxygenation of dienes gave bicyclic endoperoxides, which were reduced with thiourea to the corresponding 1,4-diols with cis-configuration. Lactonization of the remaining double bond by oxidative addition of acetic acid to the double bond in the presence of Mn(OAc)₃ followed by lactone ring-opening reaction gave the target branched carbasugars.     

Synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses and 1-amino-5-deoxypentofuranoses: en route to fluorinated carbanucleosides

The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses and 1-amino-5-deoxypentofuranoses is described. The sequence involves an addition of PhSeCF₂TMS to carbohydrate-derived aldehydes or their corresponding tert-butanesulfinylimines followed by a radical cyclization. Optimized conditions for the PhSeCF₂TMS addition to α-chiral aldehydes have been disclosed and its unusual diastereoselectivity is discussed. Application of the sequence using Ellman's auxiliary allows a more direct access to 1-aminopentose analogues with a complete control of the pseudo-anomeric center configuration.     

Syntheses of (−)-gabosine A, (+)-4-epi-gabosine A, (−)-gabosine E, and (+)-4-epi-gabosine E

(+)-4-epi-Gabosine A 1 and (−)-gabosine A 2 have been synthesized starting from methyl α,d-glucopyranoside and methyl α,d-mannopyranoside, respectively, by utilizing Pd(0) catalyzed Stille coupling as the key step. On the other hand, syntheses of (+)-4-epi-gabosine E 3 and (−)-gabosine E 4 have been accomplished from methyl α,d-glucopyranoside and from methyl α,d-mannopyranoside, respectively, by utilizing DMAP catalyzed Morita-Baylis-Hillman reaction as the key step. Presence of acetyl group at C-6 position of sugar derived cyclic enone prevented the aromatization of MBH adduct. A plausible mechanism is also described.     

Medium-ring aminocyclitols: a concise synthesis of nine-membered aminocarbasugar analogs and the solid-state supramolecular architectures of two key precursors

A stereocontrolled synthesis of nine-membered aminocarbasugar analogs (amino-cyclononanoses) from a rigid bicyclo[4.3.1]deca-2,4-dien-10-one platform, harboring a latent functionalized cyclononane ring, is described.     

First synthesis of 4a-carba-β-d-galactofuranose

The synthesis of 4a-carba-β-d-galactofuranose is described starting from diacetone glucose. The key ring-closure step was carried out by metathesis to form a cyclopentene. Catalytic hydrogenation of the CC double bond gave the galacto configured saturated carbahexofuranose with excellent diastereoselectivity.     

Enzyme‐Catalyzed Stereoselective Synthesis of Two Novel Carbasugar Derivatives

Enzymatic resolution of racemic 1,4,5,6‐tetrachloro‐2‐(hydroxymethyl)‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐ene (rac‐ 1 ) using various lipases in vinyl acetate as acetyl source was studied. The obtained enantiomerically enriched (+)‐(1,4,5,6‐tetrachloro‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐en‐2‐yl)methyl acetate ((+)‐ 2 ; 94% ee), upon treatment with Na in liquid NH₃, followed by Amberlyst‐15 resin in acetone, provided (−)‐5‐(hydroxymethyl)bicyclo[2.2.1]hept‐2‐en‐7‐one ((−)‐ 7 ), which is a valuable precursor for the synthesis of carbasugar derivatives. Subsequent Baeyer–Villiger oxidation afforded a nonseparable mixture of bicyclic lactones, which was subjected to LiAlH₄ reduction and then acetylation. The resultant compounds (−)‐ 11 and (+)‐ 12 were submitted to a cis‐hydroxylation reaction, followed by acetylation, to afford the novel carbasugar derivatives (1S,2R,3S,4S,5S)‐4,5‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐( 13 )) and (1R,3R,4R,6R)‐4,6‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐( 14 )), respectively, with pseudo‐C₂‐symmetric configuration. The absolute configuration of enantiomerically enriched unreacted alcohol (−)‐ 1 (68% ee) was determined by X‐ray single‐crystal analysis by anchoring optically pure (R)‐1‐phenylethanamine. Based on the configurational correlation between (−)‐ 1 and (+)‐ 2 , the absolute configuration of (+)‐ 2 was determined as (1R,2R,4S).     

Synthesis of carbadisaccharide mimics of galactofuranosides

A partially protected carbagalactofuranose was converted into a 1,2-anhydro derivative. This epoxide was opened with alcohol nucleophiles under Lewis acid catalysis to give β-carbagalactofuranose pseudodisaccharides with excellent regioselectivity.     

A concise route to (−)-shikimic acid and (−)-5-epi-shikimic acid, and their enantiomers via Barbier reaction and ring-closing metathesis

A simple route for the synthesis of naturally occurring (−)-shikimic acid, (−)-5-epi-shikimic acid, and their enantiomers from d-ribose-derived enantiomeric aldehydes 8a and 8b by employing Barbier reaction and ring-closing metathesis as key steps has been developed.