Presentation Title

Selective Acylation of Alkyl Polyamines to Increase Drug Payloads

Start Date

November 2016

End Date

November 2016

Location

Surge 173

Type of Presentation

Oral Talk

Abstract

Amide coupling reactions provide a reliable means to quickly, reproducibly, and cost effectively synthesize drug libraries containing selected variations of simple organic compounds for future biological testing. A range of alkyl polyamines were selectively acylated with short chain fatty acids and multiple payloads of a single drug. The resulting dendrons were intended to produce differential cell uptake, increased drug payload delivery, and differing means of administration. 3,4,5-Trimethoxybenzoic acid (gallic acid) was chosen as the drug payload due to its anti-oxidative and anti-fungal properties. Decanoic acid was coupled to secondary amines to yield fat-like products that are insoluble in aqueous and organic solvents. Hexanoic acid was coupled to secondary amines to yield amorphous solids with appreciable solubility in organic solvents including alcohols. These short-chain fatty acid derivatives displayed a potential for topical administration of the drug moiety. Gallic acid and the short-chain fatty acids were selectively coupled to primary and secondary amines in common organic solvents using classic peptide coupling reagents: DCC to form anhydrides, NHS to form activated esters, and acid chloride derivatives. The products were purified through acid/base extractions, preparative TLC, centrifugal chromatography, and recrystallization. The purified products were characterized via H-NMR, IR spectroscopy, and temperature dependent H-NMR.

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Nov 12th, 3:15 PM Nov 12th, 3:30 PM

Selective Acylation of Alkyl Polyamines to Increase Drug Payloads

Surge 173

Amide coupling reactions provide a reliable means to quickly, reproducibly, and cost effectively synthesize drug libraries containing selected variations of simple organic compounds for future biological testing. A range of alkyl polyamines were selectively acylated with short chain fatty acids and multiple payloads of a single drug. The resulting dendrons were intended to produce differential cell uptake, increased drug payload delivery, and differing means of administration. 3,4,5-Trimethoxybenzoic acid (gallic acid) was chosen as the drug payload due to its anti-oxidative and anti-fungal properties. Decanoic acid was coupled to secondary amines to yield fat-like products that are insoluble in aqueous and organic solvents. Hexanoic acid was coupled to secondary amines to yield amorphous solids with appreciable solubility in organic solvents including alcohols. These short-chain fatty acid derivatives displayed a potential for topical administration of the drug moiety. Gallic acid and the short-chain fatty acids were selectively coupled to primary and secondary amines in common organic solvents using classic peptide coupling reagents: DCC to form anhydrides, NHS to form activated esters, and acid chloride derivatives. The products were purified through acid/base extractions, preparative TLC, centrifugal chromatography, and recrystallization. The purified products were characterized via H-NMR, IR spectroscopy, and temperature dependent H-NMR.