Recent advances in the synthesis of 4′-truncated nucleoside phosphonic acid analogues

Abstract

The synthesis of five series of 4′-truncated nucleoside phosphonic acid analogues is discussed in this review: (1) 4′-truncated furanose nucleoside phosphonic acid analogues; (2) 4′-truncated pyrrolidine nucleoside phosphonic acid analogues; (3) 4′-truncated carbocyclic nucleoside phosphonic acid analogues; (4) 4′-truncated isoxazole nucleoside phosphonic acid analogues; (5) 4′-truncated miscellaneous nucleoside phosphonic acid analogues. Five different ways are used to make the phosphonate moiety: (i) Michaelis-Arbuzov reaction of RX (X = Br, I, OTf) with trialkyl phosphate; (ii) Lewis acid catalyzed Michaelis-Arbuzov reaction of glycoside with trialkyl phosphite; (iii) nucleophilic addition of a dialkyl phosphite to a carbonyl group; (iv) direct coupling reaction with amino alkyl phosphonate; (v) de novo synthesis of phosphonated-isoxazole and 1,3-dioxolane heterocycles from phosphonated starting materials. Their biological activity results are briefly discussed.