Synthesis of the indole nucleoside antibiotics neosidomycin and SF-2140

Abstract

The indole nucleoside antibiotics neosidomycin 5 and SF-2140 3 have been synthesized. Methyl 4-deoxy-2,3-O-isopropylidene-α-D-lyxo-hexopyranoside 8 was converted into methyl 1-chloro-1,4-dideoxy-2,3-di-O-pivaloyl-α-D-lyxo-hexopyranuronate 33 in five steps. Silver(I)-catalysed coupling of compound 33 with 3-(cyanomethyl)indole 20 gave stereoselectively an α-nucleoside which was converted into methyl 1-[3-(carbamoylmethyl)indol-1-yl]-1,4-dideoxy-α-D-lyxo-hexopyranuronate (neosidomycin, 5). Coupling of compound 33 to 3-cyanomethyl-4-methoxyindole 23 by the sodium salt procedure, and subsequent deacylation, gave methyl 1-(3-cyanomethyl-4-methoxyindol1-yl)-1,4-dideoxy-α-D-lyxo-hexopyranuronate (SF-2140, 3). Neosidomycin, SF-2140, and their O-acyl derivatives adopt a conformation which differs from that of 1-(6-O-benzoyl-4-deoxy-2,3-O-pivaloyl-α-D-lyxo-hexopyranosyl)-3-(cyanomethyl)indole 29, in which the methyl uronate grouping of the antibiotics is present at a lower oxidation level.