A simple one pot synthesis of 1‐(s‐triazolo[4,3‐x]azinyl‐3)‐substituted polyols

Abstract

Open‐chain C‐nucleosides, 1‐(s‐triazolo[4,3‐x]azinyl‐3)polyols 13–18 were prepared by one‐pot synthesis from hydrazinoazines 20a,c and various D‐aldoses 1–6. No protective groups were required for these transformations. 1‐(s‐Triazolo[4,3‐b]pyridazinyl‐3)‐D‐xylo‐tetritol (15a) was isolated and characterised in the form of its 4‐O‐triphenylmethyl derivative 19. Reaction of hydrazinopyridazines 20a,b with methyl 2,3‐di‐O‐acetyl‐L‐threuronate (22), followed by treatment with bromine, gave the corresponding (2R,3S)‐2,3‐diacetoxy‐3‐(s‐triazolo[4,3‐b]pyridazinyl‐3)propanoic acid methyl esters 24a,b. Acetonisation of 1‐(6‐chloro‐s‐triazolo[4,3‐b]pyridazinyl‐3)‐D‐gluco‐pentitol (17a) gave a mixture of isomeric bis‐acetonides 25 and 26, while acetonisation of 1‐(6‐chloro‐s‐triazolo[4,3‐b]pyridazinyl‐3)‐D‐manno‐pentitol (18a) gave acetonide 27 as a single isomer.

Synthesis of heteroaryl substituted α‐amino acid derivatives, polyols, and related compounds

“…In the case of the unsaturated aldehyde 91, the oxidation step had to be performed with lead tetraacetate. In this manner, the corresponding cyclic 1,2,4-triazolo[4,3-b]pyridazinyl substituted polyols 92-97 were obtained in 44-76% yields [46,47] (Scheme 18).…”

“…Synthesis of partially protected polyols might be of synthetic importance, since selective intramolecular cyclization of the polyol chain would lead to C-nucleoside analogs. On the other hand, the formation new fused ring by cyclization of the polyol chain to the pyridazine ring would furnish fused analogs of iminopolyols [46,48] (Scheme 20).…”