Synthetic Applications of the Chitin-Derived Platform 3-Acetamido-5-Acetylfuran (3A5AF)

Abstract

Chitin (34) is the second most abundant biopolymer on earth. It is readily attainable from millions of tonnes of crustacean shell waste generated by the global seafood industry. The production of 3-acetamido-5-acetylfuran (3A5AF, 63) from chitin (34) emphasises its potential as a source of small molecules that contain biorenewable nitrogen. This thesis describes several novel applications of 3A5AF (63) in the synthesis of diverse bio-based Ncompounds relevant to the chemical industry. Research commenced with the functionalisation of 3A5AF (63) to obtain a series of bio-based aminofuran derivatives that are difficult to prepare by existing synthetic methods. Functionalisation of the biorenewable nitrogen atom in 3A5AF (63) gave a variety of furans bearing different N-functional groups. The C2 and C5 sites were also readily derivatised. A synthetic method for the conversion of 3A5AF (63) into L-rednose (114), a rare 2-aminosugar found in anthracycline and angucycline antibiotics, has also been developed. This was achieved by a three-step procedure, a Noyori asymmetric hydrogenation of 3A5AF (63) gave the 4-aminofurfuryl alcohol (S)-113 that upon Achmatowicz rearrangement gave Nacetyl-L-rednose (RedNAc, 319). Final acetamide hydrolysis afforded L-rednose (114). RedNAc 319 subsequently underwent a series of different reactions to provide access to novel 2-aminosugar chemical space. The furfuryl alcohol 105 prepared from the reduction of 3A5AF (63) with sodium borohydride underwent a Piancatelli rearrangement to give the 3-aminocyclopentenone 115 that was readily converted into a variety of 4-aminocyclopentanones and 4-amino-cyclopentene-1,3-diones. Among these functionally rich compounds, 444, 456 and 458 were employed in the diversity-oriented synthesis (DOS) programme, providing a series of structurally diverse druglike N-heterocyclic compounds. Finally, we conducted a preliminary study examining the conversion of 3A5AF (63) into biobased aniline derivatives. The [4+2]-cycloaddition of 3A5AF (63) with methyl acrylate (145) in water gave the cycloadducts 590. Unfortunately, efforts to aromatise 590 into the desired aniline 594 were unsuccessful. However, the tertiary amide 118, readily prepared by methylation of 3A5AF (63), and methyl acrylate (145) did undergo a tandem [4+2]-cycloaddition-aromatisation process, giving aniline 600. Similarly, the reaction of 118 with maleimide (604) gave the aminophthalimide 605. In case of methyl vinyl ketone (281) and pbenzoquinone (472) as dienophiles, the Michael addition reaction occurred instead to provide 611 and 612, respectively.