Date of Award
Senior Scholars Paper (Open Access)
Colby College. Chemistry Dept.
Abstract This paper deals with two synthetic routes designed to yield carbon nucleosides. The C-nucleosides are compounds of potential antibiotic utility. The first approach, designed to yield 4-(2'-deoxyribofuranosyl )-1 ,2,3-triazole (1), consisted of silylation of methyl vinyl ketone (4) to give 2-trimethylsilylosy-l,3-butadiene (6), followed by a crossed aldol condensation with a heteroaromatic aldehyde to yield the aldol l. Epoxidation and cyclization of l was expected to yield the target molecule ~. The initial step, silylation of methyl vinyl ketone (4), was successful. Using model compounds the second step of the synthesis was attempted. Numerous attempts to condense (6) with 2-pyridinecarboxaldehyde (12) using a TiC1 4 catalyst proved to be unsuccessful with only unreacted 12 being recovered. The unreactivity of this system suggested a stable bidentate chelate between TiC1 4 and 2-pyridinecarboxaldehyde. Benzaldehyde (15) was used as a simpler model system. TiC1 4 promoted reaction between 15 and 6 resulted in a mixture of products, which proved very difficult to identify and separate. Fluoride ion was then exchanged for the TiC1 4 catalyst. Using phase transfer catalysts such as crown ethers and quartenary ammonium fluorides complex mixtures of reaction products were again obtained. Some of the isolated products indicated that 6 had undergone Diels-Alder reactions. The second approach towards synthesis of C-nucleosides involved elaboration of the heterocyclic unit from a protected sugar moiety . D-ribose was isopropyl ;dated to di-2,3,0-isopropylidene-D-ribofuranose (19). Tritylation of 19 yielded 2,3-di-0-isopropylidene-5-0-trityl-D-ribofuranose (20). The chloro sugar 2,3-di-0-isopropylidene-5-0-trityl-?-D-ribofuranosylchloride (21) was prepared from 20. We then planned to make the acid chloride of 21 which was expected to react with an aziridine to yield the l-acylaziridine (26). The l-acylaziridine was expected to undergo iodide catalyzed isomerization to give an oxazoline C-nucleoside. Attempts to form the acid chloride 23 were unsuccessful due to our inability to form the Grignard of 21. Present strategies towards production of the 23 involve making the nitrile of 21 and converting this to the carboxylic acid which should then give the acid chloride 23.
Nucleosides, Antibiotics, Organic compounds synthesis
Recommended CitationDavis, Jeffery, "Synthesis of carbon nucleosides : potential antibiotics" (1981). Senior Scholar Papers. Paper 63.
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