Synthetic Applications of The Chitin-Derived Platforms Dihydroxyethyl Acetamidofuran (Di-HAF) and 3-Acetamido-5-Furfuryl Aldehyde (3A5F)

Abstract

Chitin (79) is the second most abundant biopolymer on earth and a reservoir of biologically fixed nitrogen. Chitin (79) is one of the main components (20 – 30%) of crustacean shells. With an estimated six to eight million tonnes of crustacean shell waste produced yearly, converting chitin (79) into value-added compounds is desirable. As Di-HAF (101) and 3A5F (103) are easily synthesised from the monomer of chitin (79), ¬N¬-acetylglucosamine (80), these N-containing bio-based platforms could be used to synthesise an abundance of N-compounds in procedures independent of the Haber process. To begin, we demonstrated the first use of Di-HAF (101) as a chiral pool synthon in synthesising epi-leptosphaerin (266). Silylation of Di-HAF (101) gave TBDMS Di-HAF (308), which, upon photooxygenation, produced 3-acetamido-5-methoxy butenolide 309. A one-pot selective C5 reductive deoxygenation and desilylation then furnished epi-leptosphaerin (266) as a single diastereomer. Di-HAF (101) was silylated at the primary alcohol to give TBDMS Di-HAF (391) and then subjected to an Achmatowicz rearrangement to afford pyranone 393, retaining the biomass-derived stereocentre. From here, several Haber-independent 2-aminosugars and related pyranones were accessible. Additional reactions of Di-HAF (101) were investigated. A Paternò–Büchi cycloaddition of Di-HAF (101) did not give the desired dioxabicyclo[3.2.0]heptene 431a/b or 432a/b. Instead, a photoinitiated Achmatowicz rearrangement occurred, giving pyranone 390. Unexpectedly, an oxa-Pictet-Spengler reaction of Di-HAF (101) afforded difurylmethylpropane 500 rather than the anticipated furo[3,2-c]pyran 499. Finally, hydrogenation of Di-HAF (101) at atmospheric pressure gave 2,4-disubstituted tetrahydrofuran 433a/b (dr 1:1). Increasing the pressure improved the diastereomeric ratio to 1:0.5. Some investigations on the applications of 3A5F (103) towards the bio-based synthesis of penidilamine (512) were conducted. Reductive deoxygenation of 3A5F (103) gave 5-methylfuran 513. Photooxidation to 3-acetamido-5-methoxy-5-methylbutenolide 514, followed by selective C5 reductive deoxygenation, furnished 3-acetyl-5-methylbutenolide 515. Subsequent attempts at deacetylation were unsuccessful, thus, we were unable to complete the synthesis of penidilamine (512). 3A5F (103) was also used as a platform in a proposed synthesis of fritenolides D (532) and E (533). A modified Julia olefination with 2-(tridecylsulfonyl)benzo[d]thiazole (546) produced unstable vinyl furan 547. The reduction of vinyl furan 547 to 535 was unsuccessful, with only degradation occurring. Additional attempts at C-C bond formation using alternate methods were fruitless. However, when a Stetter reaction was attempted, instead of the desired 1,4-dicarbonyl 565, furfuryl ethyl ester 566 formed unexpectedly. The scope of this oxidative esterification was explored, and Haber-independent 4-amido-2-carboxylates were prepared.