A Malonyl-Based Scaffold for Conjugatable Multivalent Carbohydrate-BODIPY Presentations

Abstract

A concise synthetic route from methylmalonate to a tetravalent aliphatic scaffold has been developed. The ensuing tetra-tethered derivative is equipped with two hydroxyl groups, as well as orthogonal alkene and alkyne functionalities. The usefulness of the scaffold has been demonstrated with the preparation of two representative multivalent derivatives: (i) a tetravalent compound containing two D-mannose units, one fluorescent boron-dipyrromethene (BODIPY) dye and a suitably functionalized amino acid and (ii) by way of dimerization and saponification, a water-soluble tetramannan derivative containing two fluorescent BODIPY units. Additionally, photophysical measurements conducted on these derivatives support the viability of the herein designed single and double BODIPY-labeled carbohydrate-based clusters as fluorescent markers.

Effect of Short PEG on Near-Infrared BODIPY-Based Activatable Optical Probes

“…Accordingly, hydrophilicity is one of the most important factors in successful conjugation chemistry, and various molecular modifications have been attempted to increase hydrophilicity. To this end, the addition of sulfonic acid, carbohydrate, carboxylic acid, or ammonium salt motifs to BODIPY-based dyes has been reported. − PEGylation is also a well-established method to improve in vivo pharmacokinetics and in vivo stability by conferring higher water solubility. − In this study, NMP14 was highly hydrophobic and hardly reacted with antibodies in the aqueous phase. The addition of short PEG chains to NMP14 increased hydrophilicity and allowed NMP13 to conjugate to antibodies.…”

Bodipy-carbohydrate systems: synthesis and bio-applications

“…66 In its actual form 40 was subjected to a double glycosylation and cycloaddition with BODIPY 18e (depicted in Scheme 4 and shown in Scheme 9) to lead to compound 41 . 67 Its reaction with the α-aminoacid 42 gave the fluorescent divalent mannoside 43 , while its dimerization and subsequent deprotection led to the BODIPY-labelled tetramannan derivative 44 , with boron–oxygen substitution, both obtained by a cross-metathesis approach. The spectral properties of such single and double BODIPY-labeled carbohydrate-based clusters 43 and 44 support their use as fluorescent markers.…”

Bringing Color to Sugars: The Chemical Assembly of Carbohydrates to BODIPY Dyes

“…Along this line, we used azido‐BODIPY 22 in conjunction with an alkynyl tetravalent malonyl‐derived disaccharide 31 , bearing an additional terminal olefin group, in the preparation of BODIPY disaccharide 32 (Scheme 6). [38] …”

“…Along this line, we used azido-BODIPY 22 in conjunction with an alkynyl tetravalent malonyl-derived disaccharide 31, bearing an additional terminal olefin group, in the preparation of BODIPY disaccharide 32 (Scheme 6). [38] This multivalent carbohydrate presentation could still be duplicated by cross-metathesis dimerization (2 nd generation Hoveyda-Grubbs' catalyst) of 32, to yield tetrasaccharidic ensemble 33, containing two BODIPY units (Scheme 7). Debenzoylation of the latter unexpectedly yielded watersoluble bis-BODIPY-tetramannan 34 (as a mixture of diastereomers) where the fluorine atoms at boron in the BODIPY had been replaced by the C-4 and C-6 hydroxyl groups of the two mannose residues (Scheme 7).…”