John L. Grutsch

Synthesis of 7-cyano- and 7-acetamido-indoles via cyanocarbonation/hydrogenation of 7-formyl indole

A procedure for the synthesis of 7-cyano and 7-acetamido indoles via cyanocarbonation/hydrogenation of 7-formyl indole is presented. The process can be efficiently scaled up to provide multigram quantities of the desired compounds in good yield. A small survey of substrate scope indicates that the reaction may prove generally useful for the synthesis of aryl acetonitriles.

STUDIES ON THE PHOSPHORYLATION OF LY303366

Abstract Phosphorylation of LY303366 ( 1 ) was studied in THF and DMF. Benzyl phosphate 2 could be prepared in excellent yield using LiOH as the base. Both 2 and the derived phosphonic acid monosodium salt 3 were prone to undergo hydrolytic dephosphorylation.

Selective methylphosphonylation of an echinocandin B analog derived from LY303366

Abstract Echinocandin B (ECB) analog 1c was methylphosphonylated with the new reagent dimethyldiphosphonate 7 . Selective functionalization of the phenol group was achieved in the presence of 11 other reactive alcohol and amide groups. The phosphonylation was best conducted in a mixture of THF and DMF using lithium t-butoxide as base. Methylphosphonate diester 1d was deprotected by hydrogenolysis to afford methylphosphonate monoester 1e , a potential prodrug for ECB analog 1c .